Inclusion Criteria:
* Bodyweight \>= 10 kilogram (kg)
* Confirmed diagnosis of UC
* Demonstrated intolerance or inadequate response (IR) to one or more of the following categories of drugs: systemic corticosteroids, immunomodulators, and/or biologic therapies as outlined in the protocol
Exclusion Criteria:
* Monogenic disorder pertaining to infant onset inflammatory bowel disease (IBD)
* Current diagnosis of Crohn's disease (CD), abdominal/intrabdominal/perianal fistula and/or abscess, indeterminant colitis, IBD-unclassified, microscopic colitis, ischemic colitis, infectious colitis, radiation colitis, or active diverticular disease
* Presence of an ostomy or ileoanal pouch
* Current diagnosis or suspicion of primary sclerosing cholangitis
* Any major surgery within 6 weeks prior to screening or a major planned surgery during the study
* Active tuberculosis (TB) infection suggested by positive TB testing, clinical symptoms, and/or chest imaging (X-ray or CT)
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Inclusion Criteria:
* Bodyweight \>= 10 kilogram (kg)
* Confirmed diagnosis of UC
* Moderately to severely active UC, defined as modified Mayo Score (mMS) or 5 to 9 points, including endoscopic score of 2 or 3, confirmed by centrally read endoscopy (flexible sigmoidoscopy or colonoscopy)
* Demonstrated intolerance or inadequate response (IR) to one or more of the following categories of drugs: systemic corticosteroids, immunomodulators, and/or biologic therapies as outlined in the protocol
Exclusion Criteria:
* Monogenic disorder pertaining to infant onset inflammatory bowel disease (IBD)
* Current diagnosis of Crohn's disease (CD), abdominal/intrabdominal/perianal fistula and/or abscess, indeterminant colitis, IBD-unclassified, microscopic colitis, ischemic colitis, infectious colitis, radiation colitis, or active diverticular disease
* Presence of an ostomy or ileoanal pouch
* Current diagnosis or suspicion of primary sclerosing cholangitis
* Any major surgery within 6 weeks prior to screening or a major planned surgery during the study
* Active tuberculosis (TB) infection suggested by positive TB testing, clinical symptoms, and/or chest imaging (X-ray or CT)
Inclusion Criteria:
* Histologically confirmed large B-cell lymphoma (de novo or transformed from FL) with one of the following diagnoses according to World Health Organization, fifth edition: DLBCL Not Otherwise Specified (NOS); High-Grade B-Cell Lymphoma (HGBL), NOS; DLBCL/HGBL with MYC and BCL2 rearrangements
* R/R disease, defined as: relapsed = disease that has recurred following a response that lasted \>/= 6 months after completion of the last line of therapy; refractory = disease that did not respond to or that progressed \< 6 months after completion of the last line of therapy
* At least one line of prior systemic therapy
* Participants who have failed only one prior line of therapy must not be a candidate for high-dose chemotherapy followed by autologous stem cell transplant (ASCT)
* At least one bi-dimensionally measurable (\> 1.5 cm) nodal lesion, or one bi-dimensionally measurable (\> 1 cm) extranodal lesion, as measured on CT scan
* Eastern Cooperative Oncology Group (ECOG) status of 0, 1, or 2
* According to the investigator's judgment, participants should be able to receive the step-up dose regimen in an outpatient setting
* Adequate hematologic and renal function
Exclusion Criteria:
* Prior enrollment in Studies GO41943 (NCT04313608), GO41944 (STARGLO; NCT04408638), or Study GO44900 (NCT06624085)
* Participant has failed only one prior line of therapy and is a candidate for stem cell transplantation
* Any history of Waldenstrom's macroglobulinemia
* Primary mediastinal B-cell lymphoma
* History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies (or recombinant antibody-related fusion proteins) or known sensitivity or allergy to murine products
* Contraindication to obinutuzumab, gemcitabine or oxaliplatin, or tocilizumab
* Prior treatment with glofitamab or other bispecific antibodies targeting both CD20 and CD3
* Prior treatment with gemcitabine or oxaliplatin
* Peripheral neuropathy or paresthesia assessed to be Grade \>/= 2 according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 at enrollment
* Treatment with radiotherapy, chemotherapy, immunotherapy, immunosuppressive therapy, or any investigational agent for the purposes of treating cancer within 2 weeks prior to first study treatment
* Treatment with monoclonal antibodies for the purposes of treating cancer within 4 weeks prior to first study treatment
* Primary or secondary CNS lymphoma at the time of recruitment
* Prior CNS involvement that has been definitively treated and confirmed via magnetic resonance imaging (MRI) or cerebrospinal fluid analysis to be in complete remission is permissible
* Current or history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease
* History of other primary malignancy, with exceptions defined by the protocol
* Significant or extensive cardiovascular disease
* Significant pulmonary disease (including moderate or severe obstructive pulmonary disease)
* Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment or any major episode of infection (as evaluated by the investigator) within 4 weeks prior to the first study treatment
* Positive for: severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); tuberculosis; hepatitis B virus (HBV); hepatitis C virus (HCV); chronic active Epstein-Barr viral infection
* Known or suspected history of hemophagocytic lymphohistiocytosis (HLH) or progressive multifocal leukoencephalopathy
* Adverse events from prior anti-cancer therapy that have not resolved to Grade 1 or better (with the exception of alopecia and anorexia)
* Administration of a live, attenuated vaccine within 4 weeks before first study treatment administration or anticipation that such a live, attenuated vaccine will be required during the study
* Prior solid organ transplantation or prior allogenic stem cell transplant
* Active autoimmune disease requiring treatment
* Prior treatment with systemic immunosuppressive medications (including, but not limited to, cyclophosphamide, azathioprine, methotrexate, thalidomide, and antitumor necrosis factor agents), within 4 weeks prior to first dose of study treatment
* Ongoing systemic corticosteroid use which, in the opinion of the investigator, puts the participant at increased risk of steroid-related iatrogenic adrenal insufficiency
* Recent major surgery (within 4 weeks before the first study treatment) other than for diagnosis
* Clinically significant history of cirrhotic liver disease
* Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or renders the participant at high-risk from treatment complications
* Pregnancy or breastfeeding, or intention of becoming pregnant during the study or within 18 months after the final dose of study treatment
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Inclusion Criteria:
* Life expectancy \>= 12 weeks.
* For participants in the Glofit-GemOx combination therapy cohort (Cohort A) and the glofitamab monotherapy cohort (Cohort B), participant with histologically confirmed diffuse large B-cell lymphoma, (de novo or transformed from a follicular lymphoma (FL); participants with transformed FL must be relapsed or refractory (R/R) to standard therapies of transformed FL) with one of the following diagnoses according to World Health Organization, fifth edition (Alaggio et al. 2022). A fresh biopsy at study entry is not mandated. The histology can be confirmed based on fresh biopsy, or pathology report from a previous biopsy or an assessment of archival tumor tissue.
1. Diffuse Large B-Cell Lymphoma (DLBCL) not otherwise specified (NOS).
2. High-Grade B-Cell Lymphoma (HGBL), NOS.
3. DLBCL/HGBL with myelocytomatosis proto-oncogene (MYC) and B-cell lymphoma 2 (BCL2) rearrangements.
* R/R disease, defined as: relapsed = disease that has recurred following a response that lasted \>/= 6 months after completion of the last line of therapy; refractory = disease that did not respond to or that progressed \< 6 months after completion of the last line of therapy.
* At least one line of prior systemic therapy.
* Participants who have failed one prior line of therapy (eligible to Cohort A) must not be a candidate for high-dose chemotherapy followed by autologous stem cell transplant.
* At least one bi-dimensionally measurable (\> 1.5 cm) nodal lesion, or one bi-dimensionally measurable (\> 1 cm) extranodal lesion, as measured on CT scan.
* Eastern Cooperative Oncology Group (ECOG) status of 0, 1, or 2.
* According to the investigator's judgment, participants should be able to receive the step-up dose regimen in an outpatient setting.
Exclusion Criteria:
* Prior enrollment in Studies GO41943 (NCT04313608), GO41944 (STARGLO; NCT04408638), or Study GO44900 (NCT06624085).
* Participant has failed only one prior line of therapy and is a candidate for stem cell transplantation.
* Any history of Waldenstrom's macroglobulinemia.
* Primary mediastinal B-cell lymphoma.
* History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies (or recombinant antibody-related fusion proteins) or known sensitivity or allergy to murine products.
* Contraindication to obinutuzumab, gemcitabine or oxaliplatin, or tocilizumab. For participants in the monotherapy cohort (Cohort B), participants with contraindication to obinutuzumab or tocilizumab will be excluded.
* Prior treatment with glofitamab or other bispecific antibodies targeting both CD20 and CD3.
* For the Glofit-GemOx combination therapy cohort (Cohort A), prior treatment with gemcitabine or oxaliplatin.
* For the Glofit-GemOx combination therapy cohort (Cohort A), peripheral neuropathy or paresthesia assessed to be Grade \>= 2 according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 at enrolment.
* Treatment with radiotherapy, chemotherapy, immunotherapy, immunosuppressive therapy, or any investigational agent for the purposes of treating cancer within 2 weeks prior to first study treatment.
* Treatment with monoclonal antibodies for the purposes of treating cancer within 4 weeks prior to first study treatment.
* Primary or secondary CNS lymphoma at the time of recruitment.
* Prior CNS involvement that has been definitively treated and confirmed via magnetic resonance imaging (MRI) or cerebrospinal fluid analysis to be in complete remission is permissible.
* Current or history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease.
* History of other primary malignancy, with exceptions defined by the protocol.
* Significant or extensive cardiovascular disease.
* Significant pulmonary disease (including moderate or severe obstructive pulmonary disease).
* Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment or any major episode of infection (as evaluated by the investigator) within 4 weeks prior to the first study treatment.
* Positive for: severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); tuberculosis; hepatitis B virus (HBV); hepatitis C virus (HCV); chronic active Epstein-Barr viral infection.
* Known or suspected history of hemophagocytic lymphohistiocytosis (HLH) or progressive multifocal leukoencephalopathy.
* Adverse events from prior anti-cancer therapy that have not resolved to Grade 1 or better (with the exception of alopecia and anorexia).
* Administration of a live, attenuated vaccine within 4 weeks before first study treatment administration or anticipation that such a live, attenuated vaccine will be required during the study.
* Prior solid organ transplantation or prior allogenic stem cell transplant.
* Active autoimmune disease requiring treatment.
* Prior treatment with systemic immunosuppressive medications (including, but not limited to, cyclophosphamide, azathioprine, methotrexate, thalidomide, and antitumor necrosis factor agents), within 4 weeks prior to first dose of study treatment.
* Ongoing systemic corticosteroid use which, in the opinion of the investigator, puts the participant at increased risk of steroid-related iatrogenic adrenal insufficiency.
* Recent major surgery (within 4 weeks before the first study treatment) other than for diagnosis.
* Clinically significant history of cirrhotic liver disease.
* Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or renders the participant at high-risk from treatment complications.
* Pregnancy or breastfeeding, or intention of becoming pregnant during the study or within 18 months after the final dose of study treatment.
Inclusion Criteria:
* For Cohorts 1-8: Has a definitive diagnosis of DMD based on documented clinical findings and prior genetic testing.
* Cohort 8: Non-ambulatory per protocol-specified criteria at the time of Screening, has a performance upper limb (PUL) entry item score ≥3 at the Screening visit and has a total PUL score of ≥20 and ≤40 at the time of Screening.
* Cohorts 1, 2, 3, 5, 7 and 8 only: Stable dose equivalent of oral glucocorticoids for at least 12 weeks before screening and the dose is expected to remain constant (except for modifications to accommodate changes in weight) throughout the first year of the study.
* Cohort 1: Is ambulatory, and ≥4 to \<8 years of age at the time of Screening.
* Cohort 2: Is ambulatory, and ≥8 to \<18 years of age at the time of Screening.
* Cohort 3: Non-ambulatory per protocol specified criteria at the time of Screening.
* Cohort 4: Is ambulatory and ≥3 to \<4 years of age at the time of Screening.
* Cohort 5a: Is ambulatory and ≥4 to \<9 years of age with time to rise from the floor ≤7 seconds at the screening visit.
* Cohort 5b: Non-ambulatory per protocol specified criteria at the time of Screening.
* Cohort 6: Is ambulatory, and ≥2 to \<3 years of age at the time of Screening.
* Cohort 7: Non-ambulatory per protocol-specified criteria at the time of Screening.
* Cohorts 4 and 6: Do not yet require use of chronic steroids for treatment of their DMD, in the opinion of the Investigator, and are not receiving steroids at the time of Screening.
* Genetic mutation inclusion criteria vary by cohort.
All Cohorts:
* Ability to cooperate with motor assessment testing.
* rAAVrh74 antibody titers are not elevated as per protocol-specified requirements.
Exclusion Criteria:
* Cohort 8: Any confounding factors that would prevent the use of oral sirolimus including a known hypersensitivity to sirolimus or any of its excipients.
* Has a concomitant illness, autoimmune disease, chronic drug treatment, and/or cognitive delay/impairment that in the opinion of the Investigator creates unnecessary risks for gene transfer.
* Exposure to gene therapy, investigational medication, or any treatment designed to increase dystrophin expression within protocol-specified time limits.
* Abnormality in protocol-specified diagnostic evaluations or laboratory tests.
Note: Other inclusion/exclusion criteria apply.
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Inclusion Criteria:
* For Cohorts 1-8: Has a definitive diagnosis of DMD based on documented clinical findings and prior genetic testing.
* Cohort 8: Non-ambulatory per protocol-specified criteria at the time of Screening, has a performance upper limb (PUL) entry item score ≥2 at the Screening visit and has a total PUL score of ≥12 and ≤40 at the time of Screening.
* Cohorts 1, 2, 3, 5, 7 and 8 only: Stable dose equivalent of oral glucocorticoids for at least 12 weeks before screening and the dose is expected to remain constant (except for modifications to accommodate changes in weight) throughout the first year of the study.
* Cohort 1: Is ambulatory, and ≥4 to \<8 years of age at the time of Screening.
* Cohort 2: Is ambulatory, and ≥8 to \<18 years of age at the time of Screening.
* Cohort 3: Non-ambulatory per protocol specified criteria at the time of Screening.
* Cohort 4: Is ambulatory and ≥3 to \<4 years of age at the time of Screening.
* Cohort 5a: Is ambulatory and ≥4 to \<9 years of age with time to rise from the floor ≤7 seconds at the screening visit.
* Cohort 5b: Non-ambulatory per protocol specified criteria at the time of Screening.
* Cohort 6: Is ambulatory, and ≥2 to \<3 years of age at the time of Screening.
* Cohort 7: Non-ambulatory per protocol-specified criteria at the time of Screening.
* Cohorts 4 and 6: Do not yet require use of chronic steroids for treatment of their DMD, in the opinion of the Investigator, and are not receiving steroids at the time of Screening.
* Genetic mutation inclusion criteria vary by cohort.
All Cohorts:
* Ability to cooperate with motor assessment testing.
* rAAVrh74 antibody titers are not elevated as per protocol-specified requirements.
Exclusion Criteria:
* Cohort 8: Any confounding factors that would prevent the use of oral sirolimus including a known hypersensitivity to sirolimus or any of its excipients.
* Has a concomitant illness, autoimmune disease, chronic drug treatment, and/or cognitive delay/impairment that in the opinion of the Investigator creates unnecessary risks for gene transfer.
* Exposure to gene therapy, investigational medication, or any treatment designed to increase dystrophin expression within protocol-specified time limits.
* Abnormality in protocol-specified diagnostic evaluations or laboratory tests.
Note: Other inclusion/exclusion criteria apply.
Inclusion Criteria:
* Diagnosis of severe (Factor VIII \[FVIII\] coagulant activity \<1 IU/dL) or moderate (FVIII coagulant activity ≥1 IU/dL and ≤5 IU/dL) congenital hemophilia A with or without inhibitors against FVIII
* Participants with FVIII inhibitors: participants using recombinant activated factor VII (rFVIIa) or willing to switch to rFVIIa as primary bypassing agent for the treatment of breakthrough bleeds, trauma, or procedures
* Historic local FVIII inhibitor test results being available during screening to confirm any previous inhibitor history and current status
* Participants who previously successfully completed immune tolerance induction (ITI) must have done so at least 5 years before screening and must have no evidence of inhibitor recurrence (permanent or temporary) since. FVIII tolerance defined as \<0.6 Bethesda unit (BU)/mL (\<1.0 BU/mL only for laboratories with an historical sensitivity cutoff for inhibitor detection of 1.0 BU/mL) and in vivo recovery \>66%
* Documentation of number and type of bleeding episodes in the last 24 weeks prior to enrollment
* Adequate hematologic function, defined as platelet count ≥100,000 cells/μL and hemoglobin ≥11 g/dL at the time of screening
* Adequate hepatic function defined as total bilirubin ≤1.5× age-adapted upper limit of normal (ULN) (excluding Gilbert syndrome) and both aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3× age-adapted ULN at the time of screening, and no clinical signs or known laboratory/radiographic evidence consistent with cirrhosis. For patients with Gilbert syndrome, bilirubin should be \<4 mg/dL or 68.4 umol/L at the time of screening.
* For Part 1 only: Adequate renal function, defined as serum creatinine ≤2.5× age-adapted ULN and calculated creatinine clearance ≥30 mL/min by Cockroft-Gault formula
* For Part 2 only: Adequate renal function, defined as serum creatinine ≤1.5× age-adapted ULN. When the serum creatinine is ≥1.5× ULN, creatinine clearance by Bedside Schwartz formula must be \>70 mL/min/1.73m\^2.
* Willingness and ability to comply with schedules visits, treatment plans, laboratory tests, and other study procedures
Exclusion Criteria:
* Inherited or acquired bleeding disorders other than congenital hemophilia A
* Ongoing or planned ITI therapy
* Previous or current treatment for thromboembolic disease (with the exception of previous catheter-associated thrombosis for which anti-thrombotic treatment is not currently ongoing) or signs of thromboembolic disease
* At high risk for thrombotic microangiopathy (TMA), including past personal or family history of TMA, in the investigator's judgment
* For Part 1 only: Personal history of ischemic heart disease, cerebrovascular disease, or diabetes mellitus
* For Part 1 only: Strong family history of ischemic heart disease or cerebrovascular disease (i.e., first degree relatives such as parents, full siblings, or children): male relatives diagnosed under the age of 55 years and females under the age of 65 years
* For Part 1 only: Previous or concomitant malignancies or leukemia
* Other conditions (e.g., autoimmune conditions such as Systemic Lupus erythematosus and other systemic inflammatory disorders) that may currently increase the risk of bleeding or thrombosis
* History of clinically significant allergies
* Receipt of any of the following:
i) An investigational drug to treat or reduce the risk of hemophilic bleeds within 5 half-lives of last drug administration or normalization of targeted parameters (e.g., anti-thrombin), whichever is longer; ii) A non-hemophilia-related investigational drug within last 30 days or 5 half-lives, whichever is shorter; iii) Any other investigational drug currently being administered or planned to be administered; iv) Prior gene therapy or gene therapy planned to be administered; v) Use of systemic immunomodulators (e.g., interferon or rituximab) at enrollment or planned use during the study, with the exception of anti-retroviral therapy to treat HIV.
* Protein C activity, protein S free antigen, or anti-thrombin III activity levels below the lower limit of the reference range at screening
* Known HIV infection with CD4 counts \<200 cells/μL
* History of severe allergic or anaphylactic reactions to monoclonal antibody therapy and to chimeric or humanized antibodies or fusion proteins
* Known hypersensitivity to Chinese hamster ovary cell products or to excipient content
* History or presence of an abnormal ECG that is deemed clinically significant, (e.g., complete left bundle branch block, second- or third -degree atrioventricular heart block), including atrial fibrillation or evidence of prior myocardial infarction
* QT interval corrected through use of Fridericia's formula (QTcF) \>450 ms demonstrated by at least two ECGs \>30 minutes apart
* History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias such as structural heart disease (e.g., severe left ventricular systolic dysfunction, left ventricular hypertrophy), coronary heart disease (symptomatic or with ischemia demonstrated by diagnostic testing), clinically significant electrolyte abnormalities (e.g., hypokalemia, hypomagnesemia, hypocalcemia), or family history of sudden unexplained death or long QT syndrome
* Current treatment with medications that are well known to prolong the QT interval
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Inclusion Criteria:
* Diagnosis of severe (Factor VIII coagulant activity \[FVIII:C\] \<1 IU/dL) or moderate (FVIII:C ≥1 IU/dL and ≤5 IU/dL) congenital hemophilia A with or without inhibitors against FVIII
* Participants with FVIII inhibitors: participants using recombinant activated factor VII (rFVIIa) or willing to switch to rFVIIa as primary bypassing agent for the treatment of breakthrough bleeds, trauma, or procedures
* Historic local FVIII inhibitor test results being available during screening to confirm any previous inhibitor history and current status
* Participants who previously successfully completed immune tolerance induction (ITI) must have done so at least 5 years before screening and must have no evidence of inhibitor recurrence (permanent or temporary) since. FVIII tolerance defined as \<0.6 Bethesda unit (BU)/mL (\<1.0 BU/mL only for laboratories with an historical sensitivity cutoff for inhibitor detection of 1.0 BU/mL) and in vivo recovery \>66%
* Documentation of number and type of bleeding episodes in the last 24 weeks prior to enrollment
* Adequate hematologic function, defined as platelet count ≥100,000 cells/μL and hemoglobin ≥11 g/dL at the time of screening
* Adequate hepatic function defined as total bilirubin ≤1.5× age-adapted upper limit of normal (ULN) (excluding Gilbert syndrome) and both aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3× age-adapted ULN at the time of screening, and no clinical signs or known laboratory/radiographic evidence consistent with cirrhosis. For patients with Gilbert syndrome, bilirubin should be \<4 mg/dL or 68.4 umol/L at the time of screening.
* For Part 1 only: Adequate renal function, defined as serum creatinine ≤2.5× age-adapted ULN and calculated creatinine clearance ≥30 mL/min by Cockroft-Gault formula
* For Part 2 only: Adequate renal function, defined as serum creatinine ≤1.5× age-adapted ULN. When the serum creatinine is ≥1.5× ULN, creatinine clearance by Bedside Schwartz formula must be \>70 mL/min/1.73m\^2.
* Willingness and ability to comply with schedules visits, treatment plans, laboratory tests, and other study procedures
Exclusion Criteria:
* Inherited or acquired bleeding disorders other than congenital hemophilia A
* Ongoing or planned ITI therapy
* Previous or current treatment for thromboembolic disease (with the exception of previous catheter-associated thrombosis for which anti-thrombotic treatment is not currently ongoing) or signs of thromboembolic disease
* At high risk for thrombotic microangiopathy (TMA), including past personal or family history of TMA, in the investigator's judgment
* For Part 1 only: Personal history of ischemic heart disease, cerebrovascular disease, or diabetes mellitus
* For Part 1 only: Strong family history of ischemic heart disease or cerebrovascular disease (i.e., first degree relatives such as parents, full siblings, or children): male relatives diagnosed under the age of 55 years and females under the age of 65 years
* For Part 1 only: Previous or concomitant malignancies or leukemia
* Other conditions (e.g., autoimmune conditions such as Systemic Lupus erythematosus and other systemic inflammatory disorders) that may currently increase the risk of bleeding or thrombosis
* History of clinically significant allergies
* Receipt of any of the following:
i) An investigational drug to treat or reduce the risk of hemophilic bleeds within 5 half-lives of last drug administration or normalization of targeted parameters (e.g., anti-thrombin), whichever is longer; ii) A non-hemophilia-related investigational drug within last 30 days or 5 half-lives, whichever is shorter; iii) Any other investigational drug currently being administered or planned to be administered; iv) Prior gene therapy or gene therapy planned to be administered; v) Use of systemic immunomodulators (e.g., interferon or rituximab) at enrollment or planned use during the study, with the exception of anti-retroviral therapy to treat HIV.
* Protein C activity, protein S free antigen, or anti-thrombin III activity levels below the lower limit of the reference range at screening
* Known HIV infection with CD4 counts \<200 cells/μL
* History of severe allergic or anaphylactic reactions to monoclonal antibody therapy and to chimeric or humanized antibodies or fusion proteins
* Known hypersensitivity to Chinese hamster ovary cell products or to excipient content
* History or presence of an abnormal ECG that is deemed clinically significant, (e.g., complete left bundle branch block, second- or third -degree atrioventricular heart block), including atrial fibrillation or evidence of prior myocardial infarction
* QT interval corrected through use of Fridericia's formula (QTcF) \>450 ms demonstrated by at least two ECGs \>30 minutes apart
* History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias such as structural heart disease (e.g., severe left ventricular systolic dysfunction, left ventricular hypertrophy), coronary heart disease (symptomatic or with ischemia demonstrated by diagnostic testing), clinically significant electrolyte abnormalities (e.g., hypokalemia, hypomagnesemia, hypocalcemia), or family history of sudden unexplained death or long QT syndrome
* Current treatment with medications that are well known to prolong the QT interval
Inclusion Criteria:
* Body weight \>/= 25 kg
* Children and adolescents must have received all childhood required vaccinations
* Female participants of childbearing potential must agree to either remain completely abstinent or to use reliable means of contraception
* Diagnosis of relapsing-remitting multiple sclerosis (RRMS)
* Expanded Disability Status Scale (EDSS) at screening: 0-5.5, inclusive
* Neurologic stability for \>/= 30 days prior to screening, and between screening and baseline
* Participants naive to prior disease-modifying therapy (DMT)
* Participants who have had at least 6 contiguous months of DMT within the past 1 year must have evidence of disease activity occurring after the full 6-month course of treatment, that is, at least one relapse or \>/= 1 Gd-enhancing lesion(s) on a T1-weighted brain MRI
Exclusion Criteria:
* Known presence or suspicion of other neurologic disorders that may mimic MS, including, but not limited to, acute disseminated encephalomyelitis, neuromyelitis optica or neuromyelitis optica spectrum disorders and any neurologic, somatic, or metabolic condition that could interfere with brain function or normal cognitive or neurological development
* Patients that are aquaporin 4 positive and myelin oligodendrocyte glycoprotein (MOG) antibody positive are not eligible to participate in the study.
* In case of an ADEM-like appearance of the first MS attack, a second attack with clear MS-like features is required.
* Infection requiring hospitalization or treatment with IV anti-infective agents
* History or known presence of recurrent or chronic infection (e.g., HIV, syphilis, tuberculosis)
* Receipt of a live or live-attenuated vaccine within 6 weeks prior to treatment allocation
* History or laboratory evidence of coagulation disorders
* Peripheral venous access that precludes IV administration and venous blood sampling
* Inability to complete a magnetic resonance imaging (MRI) scan
* History of cancer, including solid tumors, hematologic malignancies, and carcinoma in situ
* History of a severe allergic or anaphylactic reaction to humanized or murine monoclonal antibody (mAbs) or known hypersensitivity to any component of ocrelizumab solution
* Previous treatment with B-cell-targeted therapies
* Percentage of CD4 \< 30%
* Absolute Neutrophil Count \< 1.5x1000/microliter
* Lymphocyte count below the lower limit of normal (LLN) for age- and sex-specific reference range
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Inclusion Criteria:
* Age at screening between =/\>10 to \<18 years
* Body weight \>/= 25 kg
* Children and adolescents must have received all childhood required vaccinations
* Female participants of childbearing potential must agree to either remain completely abstinent or to use reliable means of contraception
* Diagnosis of relapsing-remitting multiple sclerosis (RRMS)
* Expanded Disability Status Scale (EDSS) at screening: 0-5.5, inclusive
* Participants naive to prior disease-modifying therapy (DMT)
* Participants who have had at least 6 contiguous months of DMT within the past 1 year must have evidence of disease activity occurring after the full 6-month course of treatment, that is, at least one relapse or \>/= 1 Gd-enhancing lesion(s) on a T1-weighted brain MRI
Exclusion Criteria:
* Known presence or suspicion of other neurologic disorders that may mimic MS, including, but not limited to, acute disseminated encephalomyelitis, neuromyelitis optica or neuromyelitis optica spectrum disorders and any neurologic, somatic, or metabolic condition that could interfere with brain function or normal cognitive or neurological development
* Patients that are aquaporin 4 positive and myelin oligodendrocyte glycoprotein (MOG) antibody positive are not eligible to participate in the study.
* In case of an acute disseminated encephalomyelitis (ADEM)like appearance of the first MS attack, a second attack with clear MS-like features is required.
* Infection requiring hospitalization or treatment with IV anti-infective agents
* History or known presence of recurrent or chronic infection (e.g., HIV, syphilis, tuberculosis)
* Receipt of a live or live-attenuated vaccine within 6 weeks prior to treatment allocation
* History or laboratory evidence of coagulation disorders
* Peripheral venous access that precludes IV administration and venous blood sampling
* Inability to complete a magnetic resonance imaging (MRI) scan
* History of cancer, including solid tumors, hematologic malignancies, and carcinoma in situ
* History of a severe allergic or anaphylactic reaction to humanized or murine monoclonal antibody (mAbs) or known hypersensitivity to any component of ocrelizumab solution
* Previous treatment with B-cell-targeted therapies
* Percentage of CD4 \< 30%
* Absolute Neutrophil Count \< 1.5x1000/microliter
* Lymphocyte count below the lower limit of normal (LLN) for age- and sex-specific reference range
Inclusion Criteria:
* For sites in Germany and Italy only, enrollment is restricted to participants aged 46-65 years
* A diagnosis of PPMS in accordance to the revised 2017 McDonald Criteria (Thompson et al. 2018).
* Disability progression in the 12 months prior to screening.
* Expanded Disability Status Scale (EDSS) score from 3.0 to 6.5 inclusive at screening.
* Pyramidal functional subscore \>=2 at screening.
* For participants currently receiving proton pump inhibitors (PPIs), H2-receptor antagonists (H2RAs), symptomatic treatment for MS (e.g. fampridine, cannabis) and/or physiotherapy: treatment at a stable dose during the screening period prior to the initiation of study treatment and plans to remain at a stable dose for the duration of study treatment.
* Neurologically stable for at least 30 days prior to randomization and baseline assessments.
* Ability to complete the 9-Hole Peg Test (9-HPT) for each hand in \<240 seconds.
* Ability to perform Timed 25-Foot Walk Test (T25FWT) in \<150 seconds.
* For female participants of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and refrain from donating eggs.
* For male participants: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and refrain from donating sperm.
OLE Inclusion Criteria:
* Completed the Double-Blind Treatment (DBT) phase of the study (remaining on study treatment; no other Disease-Modifying Therapy (DMT) administered) and who, in the opinion of the investigator, may benefit from treatment with fenebrutinib.
* For female participants of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and refrain from donating eggs.
* For male participants: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and refrain from donating sperm.
Exclusion Criteria:
* For participants enrolled in Germany and in Italy only: Presence of gadolinium-enhancing lesions on T1-weighted MRI (T1Gd +) lesion on the screening MRI
* Any known or suspected active infection (excluding onychomycosis) at screening, including but not limited to a positive screening test for Hepatitis B and C, an active or latent or inadequately treated infection with tuberculosis (TB), a confirmed or suspected progressive multifocal leukoencephalopathy (PML).
* Participants with a previous history of a serious Infusion-Related Reaction (IRR) (Common Terminology Criteria for Adverse Events \[CTCAE\] Grade \>= 4) and/or any hypersensitivity reaction to ocrelizumab.
* History of cancer including hematologic malignancy and solid tumors within 10 years of screening. Exceptions: Basal/squamous cell carcinoma of skin cured by excision. In situ carcinoma of the cervix successfully treated by curative therapy \>1 year prior to screening.
* Known presence of other neurological disorders, that could interfere with the diagnosis of MS or assessments of efficacy or safety during the study, clinically significant cardiovascular, psychiatric, pulmonary, renal, hepatic, endocrine, metabolic or gastrointestinal disease.
* Presence of cirrhosis (Child-Pugh Class A, B, or C)
* Chronic liver disease unless considered stable for \>6 months
* Acute liver disease
* Any concomitant disease that may require chronic treatment with systemic corticosteroids, immunosuppressants or specific medication that could impact the primary evaluation of the study.
* History of alcohol or other drug abuse within 12 months prior to screening.
* Female participants who are pregnant or breastfeeding or intending to become pregnant during the study or 6 or 12 months (as applicable from the local label for ocrelizumab) after final dose of study drug.
* Male participants intending to father a child during the study or for 28 days after final dose of study drug.
* Lack of peripheral venous access.
* Any previous treatment with immunomodulatory or immunosuppressive medication without an appropriate washout period.
* Receipt of a live or live-attenuated vaccine within 6 weeks prior to randomization.
* Immunocompromised state, history of primary or secondary (non-drug related) immunodeficiency, or history of transplantation or antirejection therapy
* Known bleeding diathesis, anemia, or history of hospitalization or transfusion for gastrointestinal (GI) bleed
* Any previous treatment with cladribine, mitoxantrone, daclizumab, alemtuzumab, or cyclophosphamide
OLE Exclusion Criteria:
* Chronic liver disease unless considered stable for \> 6 months
* Acute liver disease
→
Inclusion Criteria:
* For sites in Germany and Italy only, enrollment is restricted to participants aged 46-65 years
* A diagnosis of PPMS in accordance to the revised 2017 McDonald Criteria (Thompson et al. 2018).
* Disability progression in the 12 months prior to screening.
* Expanded Disability Status Scale (EDSS) score from 3.0 to 6.5 inclusive at screening.
* Pyramidal functional subscore \>=2 at screening.
* For participants currently receiving proton pump inhibitors (PPIs), H2-receptor antagonists (H2RAs), symptomatic treatment for MS (e.g. fampridine, cannabis) and/or physiotherapy: treatment at a stable dose during the screening period prior to the initiation of study treatment and plans to remain at a stable dose for the duration of study treatment.
* Neurologically stable for at least 30 days prior to randomization and baseline assessments.
* Ability to complete the 9-Hole Peg Test (9-HPT) for each hand in \<240 seconds.
* Ability to perform Timed 25-Foot Walk Test (T25FWT) in \<150 seconds.
* For female participants of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and refrain from donating eggs.
* For male participants: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and refrain from donating sperm.
OLE Inclusion Criteria:
* Completed the Double-Blind Treatment (DBT) phase of the study (remaining on study treatment; no other Disease-Modifying Therapy (DMT) administered) and who, in the opinion of the investigator, may benefit from treatment with fenebrutinib.
* For female participants of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and refrain from donating eggs.
* For male participants: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and refrain from donating sperm.
Exclusion Criteria:
* For participants enrolled in Germany and in Italy only: Presence of gadolinium-enhancing lesions on T1-weighted MRI (T1Gd +) lesion on the screening MRI
* Any known or suspected active infection (excluding onychomycosis) at screening, including but not limited to a positive screening test for Hepatitis B and C, an active or latent or inadequately treated infection with tuberculosis (TB), a confirmed or suspected progressive multifocal leukoencephalopathy (PML).
* Participants with a previous history of a serious Infusion-Related Reaction (IRR) (Common Terminology Criteria for Adverse Events \[CTCAE\] Grade \>= 4) and/or any hypersensitivity reaction to ocrelizumab.
* History of cancer including hematologic malignancy and solid tumors within 10 years of screening. Exceptions: Basal/squamous cell carcinoma of skin cured by excision. In situ carcinoma of the cervix successfully treated by curative therapy \>1 year prior to screening.
* Known presence of other neurological disorders, that could interfere with the diagnosis of MS or assessments of efficacy or safety during the study, clinically significant cardiovascular, psychiatric, pulmonary, renal, hepatic, endocrine, metabolic or gastrointestinal disease.
* Presence of cirrhosis (Child-Pugh Class A, B, or C)
* Chronic liver disease unless considered stable for \>6 months
* Acute liver disease
* Any concomitant disease that may require chronic treatment with systemic corticosteroids, immunosuppressants or specific medication that could impact the primary evaluation of the study.
* History of alcohol or other drug abuse within 12 months prior to screening.
* Female participants who are pregnant or breastfeeding or intending to become pregnant during the study or 6 or 12 months (as applicable from the local label for ocrelizumab) after final dose of study drug.
* Male participants intending to father a child during the study or for 28 days after final dose of study drug.
* Lack of peripheral venous access.
* Any previous treatment with immunomodulatory or immunosuppressive medication without an appropriate washout period.
* Receipt of a live or live-attenuated vaccine within 6 weeks prior to randomization.
* Immunocompromised state, history of primary or secondary (non-drug related) immunodeficiency, or history of transplantation or antirejection therapy
* Known bleeding diathesis, anemia, or history of hospitalization or transfusion for gastrointestinal (GI) bleed
* Any previous treatment with cladribine, mitoxantrone, daclizumab, alemtuzumab, or cyclophosphamide
OLE Exclusion Criteria:
* Chronic liver disease unless considered stable for \> 6 months
* Acute liver disease
* Cirrhosis (Child-pugh Class A, B or C)
* Gilbert's syndrome
Inclusion Criteria:
* Expanded Disability Status Scale (EDSS) score of 0 - 5.5 at screening
* A diagnosis of RMS in accordance with the revised 2017 McDonald Criteria
* Ability to complete the 9-hole Peg Test (9-HPT) for each hand in \< 240 seconds
* Ability to perform the Timed 25-foot Walk Test (T25FWT) in \< 150 seconds
* For female participants of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and refrain from donating eggs
* For male participants: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and refrain from donating sperm
OLE Inclusion Criteria:
* Completed the DBT phase of the study (remaining on study treatment; no other disease-modifying therapy (DMT) administered) and who, in the opinion of the investigator, may benefit from treatment with fenebrutinib
* Participants randomized to the teriflunomide treatment arm during the DBT phase must undergo the accelerated teriflunomide elimination procedure (ATEP) prior to the first administration of open-label fenebrutinib
* For female participants of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and refrain from donating eggs
* For male participants: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and refrain from donating sperm
Exclusion Criteria:
* Disease duration of \> 10 years from the onset of symptoms and an EDSS score at screening \< 2.0
* Female participants who are pregnant or breastfeeding, or intending to become pregnant
* Male participants who intend to father a child during the study
* A diagnosis of primary progressive multiple sclerosis (PPMS) or non-active secondary progressive multiple sclerosis (SPMS)
* Any known or suspected active infection at screening, including but not limited to a positive screening tests for hepatitis B (HBV) and hepatitis C (HCV), an active or latent or inadequately treated infection with tuberculosis (TB), a confirmed or suspected progressive multifocal leukoencephalopathy (PML)
* History of cancer including hematologic malignancy and solid tumors within 10 years of screening
* Known presence of other neurological disorders, that could interfere with the diagnosis of MS or assessments of efficacy or safety during the study and clinically significant cardiovascular, psychiatric, pulmonary, renal, hepatic, endocrine, metabolic or gastrointestinal (GI) disease
* Rare hereditary problems of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption
* Hypoproteinemia
* Acute liver disease
* Chronic liver disease unless considered stable for \> 6 months
* Presence of cirrhosis (Child-Pugh Class A, B, or C) or Gilbert's syndrome
* Participants with significantly impaired bone marrow function or significant anemia, leukopenia, neutropenia or thrombocytopenia
* Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study
* History of alcohol or other drug abuse within 12 months prior to screening
* History of or currently active primary or secondary (non-drug-related) immunodeficiency, including known history of human immunodeficiency virus (HIV) infection
* Inability to complete an MRI scan
* Adrenocorticotropic hormone or systemic corticosteroid therapy within 4 weeks prior to screening (inhaled and topical corticosteroids are allowed)
* Receipt of a live-attenuated vaccine within 6 weeks prior to randomization
* Any previous treatment with immunomodulatory or immunosuppressive medication without an appropriate washout period
OLE Exclusion Criteria:
* Chronic liver disease unless considered stable for \> 6 months
* Acute liver disease
→
Inclusion Criteria:
* Expanded Disability Status Scale (EDSS) score of 0 - 5.5 at screening
* A diagnosis of RMS in accordance with the revised 2017 McDonald Criteria
* Ability to complete the 9-hole Peg Test (9-HPT) for each hand in \< 240 seconds
* Ability to perform the Timed 25-foot Walk Test (T25FWT) in \< 150 seconds
* For female participants of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and refrain from donating eggs
* For male participants: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and refrain from donating sperm
OLE Inclusion Criteria:
* Completed the DBT phase of the study (remaining on study treatment; no other disease-modifying therapy (DMT) administered) and who, in the opinion of the investigator, may benefit from treatment with fenebrutinib
* Participants randomized to the teriflunomide treatment arm during the DBT phase must undergo the accelerated teriflunomide elimination procedure (ATEP) prior to the first administration of open-label fenebrutinib
* For female participants of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and refrain from donating eggs
* For male participants: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and refrain from donating sperm
Exclusion Criteria:
* Disease duration of \> 10 years from the onset of symptoms and an EDSS score at screening \< 2.0
* Female participants who are pregnant or breastfeeding, or intending to become pregnant
* Male participants who intend to father a child during the study
* A diagnosis of primary progressive multiple sclerosis (PPMS) or non-active secondary progressive multiple sclerosis (SPMS)
* Any known or suspected active infection at screening, including but not limited to a positive screening tests for hepatitis B (HBV) and hepatitis C (HCV), an active or latent or inadequately treated infection with tuberculosis (TB), a confirmed or suspected progressive multifocal leukoencephalopathy (PML)
* History of cancer including hematologic malignancy and solid tumors within 10 years of screening
* Known presence of other neurological disorders, that could interfere with the diagnosis of MS or assessments of efficacy or safety during the study and clinically significant cardiovascular, psychiatric, pulmonary, renal, hepatic, endocrine, metabolic or gastrointestinal (GI) disease
* Rare hereditary problems of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption
* Hypoproteinemia
* Acute liver disease
* Chronic liver disease unless considered stable for \> 6 months
* Presence of cirrhosis (Child-Pugh Class A, B, or C) or Gilbert's syndrome
* Participants with significantly impaired bone marrow function or significant anemia, leukopenia, neutropenia or thrombocytopenia
* Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study
* History of alcohol or other drug abuse within 12 months prior to screening
* History of or currently active primary or secondary (non-drug-related) immunodeficiency, including known history of human immunodeficiency virus (HIV) infection
* Inability to complete an MRI scan
* Adrenocorticotropic hormone or systemic corticosteroid therapy within 4 weeks prior to screening (inhaled and topical corticosteroids are allowed)
* Receipt of a live-attenuated vaccine within 6 weeks prior to randomization
* Any previous treatment with immunomodulatory or immunosuppressive medication without an appropriate washout period
OLE Exclusion Criteria:
* Chronic liver disease unless considered stable for \> 6 months
* Acute liver disease
* Cirrhosis (Child-pugh Class A, B or C)
* Gilbert's syndrome
Inclusion Criteria:
* Expanded Disability Status Scale (EDSS) score of 0 - 5.5 at screening
* A diagnosis of RMS in accordance with the revised 2017 McDonald Criteria
* Ability to complete the 9-Hole Peg Test (9-HPT) for each hand in \< 240 seconds
* Ability to perform the Timed 25-Foot Walk Test (T25FWT) in \< 150 seconds
* For female participants of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and refrain from donating eggs
* For male participants: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and refrain from donating sperm
OLE Inclusion Criteria:
* Completed the DBT phase of the study (remaining on study treatment; no other disease-modifying therapy (DMT) administered) and who, in the opinion of the investigator, may benefit from treatment with fenebrutinib
* Participants randomized to the teriflunomide treatment arm during the DBT phase must undergo the accelerated teriflunomide elimination procedure (ATEP) prior to the first administration of open-label fenebrutinib
* For female participants of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and refrain from donating eggs
* For male participants: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and refrain from donating sperm
Exclusion Criteria:
* Disease duration of \> 10 years from the onset of symptoms and an EDSS score at screening \< 2.0
* Female participants who are pregnant or breastfeeding, or intending to become pregnant
* Male participants who intend to father a child during the study
* A diagnosis of primary progressive multiple sclerosis (PPMS) or non-active secondary progressive multiple sclerosis (SPMS)
* Any known or suspected active infection at screening, including but not limited to a positive screening test for hepatitis B (HBV) and hepatitis C (HCV), an active or latent or inadequately treated infection with tuberculosis (TB), a confirmed or suspected progressive multifocal leukoencephalopathy (PML)
* History of cancer including hematologic malignancy and solid tumors within 10 years of screening
* Known presence of other neurological disorders, that could interfere with the diagnosis of MS or assessments of efficacy or safety during the study and clinically significant cardiovascular, psychiatric, pulmonary, renal, hepatic, endocrine, metabolic or gastrointestinal (GI) disease
* Rare hereditary problems of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption
* Hypoproteinemia
* Acute liver disease
* Chronic liver disease unless considered stable for \> 6 months
* Presence of cirrhosis (Child-Pugh Class A, B, or C) or Gilbert's Syndrome
* Participants with significantly impaired bone marrow function or significant anemia, leukopenia, neutropenia or thrombocytopenia
* Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study
* History of alcohol or other drug abuse within 12 months prior to screening
* History of or currently active primary or secondary (non-drug-related) immunodeficiency, including known history of human immunodeficiency virus (HIV) infection
* Inability to complete an MRI scan
* Adrenocorticotropic hormone or systemic corticosteroid therapy within 4 weeks prior to screening (inhaled and topical corticosteroids are allowed)
* Receipt of a live-attenuated vaccine within 6 weeks prior to randomization
* Any previous treatment with immunomodulatory or immunosuppressive medication without an appropriate washout period
OLE Exclusion Criteria:
* Acute liver disease
* Chronic liver disease unless considered stable for \> 6 months
→
Inclusion Criteria:
* Expanded Disability Status Scale (EDSS) score of 0 - 5.5 at screening
* A diagnosis of RMS in accordance with the revised 2017 McDonald Criteria
* Ability to complete the 9-Hole Peg Test (9-HPT) for each hand in \< 240 seconds
* Ability to perform the Timed 25-Foot Walk Test (T25FWT) in \< 150 seconds
* For female participants of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and refrain from donating eggs
* For male participants: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and refrain from donating sperm
OLE Inclusion Criteria:
* Completed the DBT phase of the study (remaining on study treatment; no other disease-modifying therapy (DMT) administered) and who, in the opinion of the investigator, may benefit from treatment with fenebrutinib
* Participants randomized to the teriflunomide treatment arm during the DBT phase must undergo the accelerated teriflunomide elimination procedure (ATEP) prior to the first administration of open-label fenebrutinib
* For female participants of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and refrain from donating eggs
* For male participants: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and refrain from donating sperm
Exclusion Criteria:
* Disease duration of \> 10 years from the onset of symptoms and an EDSS score at screening \< 2.0
* Female participants who are pregnant or breastfeeding, or intending to become pregnant
* Male participants who intend to father a child during the study
* A diagnosis of primary progressive multiple sclerosis (PPMS) or non-active secondary progressive multiple sclerosis (SPMS)
* Any known or suspected active infection at screening, including but not limited to a positive screening test for hepatitis B (HBV) and hepatitis C (HCV), an active or latent or inadequately treated infection with tuberculosis (TB), a confirmed or suspected progressive multifocal leukoencephalopathy (PML)
* History of cancer including hematologic malignancy and solid tumors within 10 years of screening
* Known presence of other neurological disorders, that could interfere with the diagnosis of MS or assessments of efficacy or safety during the study and clinically significant cardiovascular, psychiatric, pulmonary, renal, hepatic, endocrine, metabolic or gastrointestinal (GI) disease
* Rare hereditary problems of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption
* Hypoproteinemia
* Acute liver disease
* Chronic liver disease unless considered stable for \> 6 months
* Presence of cirrhosis (Child-Pugh Class A, B, or C) or Gilbert's Syndrome
* Participants with significantly impaired bone marrow function or significant anemia, leukopenia, neutropenia or thrombocytopenia
* Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study
* History of alcohol or other drug abuse within 12 months prior to screening
* History of or currently active primary or secondary (non-drug-related) immunodeficiency, including known history of human immunodeficiency virus (HIV) infection
* Inability to complete an MRI scan
* Adrenocorticotropic hormone or systemic corticosteroid therapy within 4 weeks prior to screening (inhaled and topical corticosteroids are allowed)
* Receipt of a live-attenuated vaccine within 6 weeks prior to randomization
* Any previous treatment with immunomodulatory or immunosuppressive medication without an appropriate washout period
OLE Exclusion Criteria:
* Acute liver disease
* Chronic liver disease unless considered stable for \> 6 months
* Cirrhosis (Child-Pugh Class A, B, or C)
* Gilbert's syndrome
Inclusion Criteria:
* Histologically documented, locally advanced, recurrent, or metastatic incurable solid tumors
* Participants with measurable disease according to RECIST v1.1 assessed by the investigator
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Life expectancy ≥12 weeks
* Adequate hematologic and end-organ function
* Confirmed presence of the RAS mutation(s)
Exclusion Criteria:
* Current participant or enrollment in another interventional clinical trial
* Known hypersensitivity or medical contraindication to any component of RO7673396 formulation
* Refractory nausea and vomiting, malabsorption, external biliary shunt, or significant small bowel resection that would preclude adequate study treatment absorption
* Known and untreated, or active central nervous system (CNS) metastases
* Participants with chronic diarrhea, short bowel syndrome or significant upper gastrointestinal (GI) surgery including gastric resection, a history of inflammatory bowel disease (IBD)
* Treatment with chemotherapy, immunotherapy, biologic therapy, or an investigational agent as anti-cancer therapy within 4 weeks or five half-lives prior to initiation of study treatment
* Participants who are on acid-reducing agents and unable to safely discontinue them as required in the study
* Major surgical procedure within 28 days prior to initiation of study treatment, or incomplete recovery from surgery that would interfere with the determination of safety or efficacy of study treatment, or anticipation of need for a major surgical procedure during the study
* Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
* Known clinically significant liver disease
→
Inclusion Criteria:
* Histologically documented, locally advanced, recurrent, or metastatic incurable solid tumors
* Participants with measurable disease according to RECIST v1.1 assessed by the investigator
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Life expectancy ≥12 weeks
* Adequate hematologic and end-organ function
* Confirmed presence of the RAS mutation(s)
Exclusion Criteria:
* Current participant or enrollment in another interventional clinical trial
* Known hypersensitivity or medical contraindication to any component of RO7673396 formulation
* Refractory nausea and vomiting, malabsorption, external biliary shunt, or significant small bowel resection that would preclude adequate study treatment absorption
* Known and untreated, or active central nervous system (CNS) metastases
* Participants with chronic diarrhea, short bowel syndrome or significant upper gastrointestinal (GI) surgery including gastric resection, a history of inflammatory bowel disease (IBD)
* Treatment with chemotherapy, immunotherapy, biologic therapy, or an investigational agent as anti-cancer therapy within 4 weeks or five half-lives prior to initiation of study treatment
* Participants who are on acid-reducing agents and unable to safely discontinue them as required in the study
* Major surgical procedure within 28 days prior to initiation of study treatment, or incomplete recovery from surgery that would interfere with the determination of safety or efficacy of study treatment, or anticipation of need for a major surgical procedure during the study
* A history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, non-infectious ILD/pneumonitis, or current evidence of active pneumonitis or ILD on screening chest CT scan
* Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
* Known clinically significant liver disease
Inclusion Criteria:
* Age at screening 2-11 years, inclusive
* Body weight at screening \>=10 kg
* For female patients of childbearing potential (postmenarchal): agreement to either remain completely abstinent (refrain from heterosexual intercourse) or to use a reliable means of contraception
* Diagnosed as having NMOSD with AQP4 antibody seropositive status as defined by the Wingerchuk 2015 criteria Clinical evidence of at least one documented attack (including first attack) in the last year prior to screening
* Neurological stability for \>=30 days prior to both screening and baseline
* Expanded Disability Status Scale (EDSS) 0 to 6.5
* For patients receiving a baseline immunosuppressant treatment and planning to continue on these therapies, treatment must be at stable dose for 4 weeks prior to baseline
Exclusion Criteria:
* Pregnancy or lactation
* Evidence of other demyelinating disease mimicking NMOSD
* Active or presence of recurrent bacterial, viral, fungal, mycobacterial infection, or other infection at baseline
* Evidence of chronic active hepatitis B or C
* Evidence of untreated latent or active tuberculosis (TB)
* Receipt of a live or live-attenuated vaccine within 6 weeks prior to baseline
* History of severe allergic reaction to a biologic agent
→
Inclusion Criteria:
* Age at screening 2-11 years, inclusive
* Body weight at screening \>=10 kg
* For female patients of childbearing potential (postmenarchal): agreement to either remain completely abstinent (refrain from heterosexual intercourse) or to use a reliable means of contraception
* Diagnosed as having NMOSD with AQP4 antibody seropositive status as defined by the Wingerchuk 2015 criteria Clinical evidence of at least one documented attack (including first attack) in the last year prior to screening:
* Documented history of a positive anti-AQP4 antibody test or a positive anti-AQP4 antibody test at screening;
* Neurological stability for \>=30 days prior to baseline
* Expanded Disability Status Scale (EDSS) 0 to 6.5
* For participants receiving a baseline immunosuppressant treatment and planning to continue on these therapies, treatment must be at stable dose for 4 weeks prior to baseline
Exclusion Criteria:
* Pregnancy or lactation
* Evidence of other demyelinating disease mimicking NMOSD
* Active or presence of recurrent bacterial, viral, fungal, mycobacterial infection, or other infection at baseline
* Evidence of chronic active hepatitis B or C
* Evidence of untreated latent or active tuberculosis (TB)
* Receipt of a live or live-attenuated vaccine within 6 weeks prior to baseline
* History of severe allergic reaction to a biologic agent
* IVIg or subcutaneous Ig (SCIg) within 4 weeks prior to enrollment/Day 1
Inclusion Criteria:
* PMS, in accordance with the revised 2017 McDonald criteria
* Expanded disability status scale (EDSS) at screening between 3.0 and 6.0 inclusive
Exclusion Criteria:
* MS relapse during the 6 months preceding the randomization date
* Lack of peripheral venous access
* History of alcohol or other drug abuse, in the opinion of the investigator, within 5 years prior to screening
* Inability to complete an magnetic resonance imaging (MRI)
* Contraindications to ocrelizumab mandatory pre-medications
* Treatment with intravenous immunoglobulin (IV Ig) or plasmapheresis within 12 weeks prior to screening
→
Inclusion Criteria:
* PMS, in accordance with the revised 2017 McDonald criteria
* Expanded disability status scale (EDSS) at screening between 3.0 and 6.0 inclusive
* Documented evidence of disability progression independent of relapse activity over the 2 years before the screening visit
Exclusion Criteria:
* MS relapse during the 6 months preceding the randomization date
* Lack of peripheral venous access
* History of alcohol or other drug abuse (substance use disorder) based on Diagnostic and Statistical Manual for Mental Disorders, fifth edition (DSM-5) criteria, within 5 years prior to screening
* Inability to complete a magnetic resonance imaging (MRI)
* Contraindications to ocrelizumab mandatory pre-medications
* Treatment with intravenous immunoglobulin (IV Ig) or plasmapheresis within 12 weeks prior to screening
Inclusion Criteria:
* Histologically or cytologically confirmed adenocarcinoma of the prostate without small-cell or neuroendocrine features
* Progressive metastatic CRPC, defined as any of the following: PSA progression, defined by a minimum of two rising PSA values from three consecutive assessments with an interval of at least 7 days between assessments and with a minimal starting value of PSA \>=1 ng/mL; The most recent qualifying PSA value must be determined within 14 days of enrollment; Soft tissue disease progression, defined by Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1); Bone disease progression, defined by PCWG3 criteria, with two or more new metastatic bone lesions on a whole-body radionuclide bone scan
* Treatment with at least one, but no more than one, prior second-generation ARPi (abiraterone, apalutamide, enzalutamide, darolutamide) for hormone- sensitive prostate cancer (HSPC) or CRPC
* Availability of a tumor tissue specimen that is suitable (e.g., adequate quality and quantity) for use in determining biomarker status
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
* Fasting glucose \<100 mg/dL and HbA1c \< 5.7%
Exclusion Criteria:
* Presence of liver metastasis
* Prior treatment with any phosphatidylinositol-3-kinase (PI3K), protein kinase B (AKT), or mammalian target of rapamycin (mTOR) inhibitor, or with any agent with a mechanism of action of inhibiting the PI3K/AKT/mTOR pathway
* Type 1 or Type 2 diabetes mellitus
* Prior treatment for mCRPC with cytotoxic chemotherapy or novel hormonal treatments (e.g., androgen receptor degraders, CYP11 inhibitors), with the following treatments permitted: Prior docetaxel in mHSPC, providing no evidence of disease progression occurred during treatment or within 6 months of treatment completion; Prior docetaxel in the adjuvant or neoadjuvant setting providing no evidence of disease progression occurred during treatment or within 12 months of treatment completion; Prior treatment with sipuleucel-T, with the last dose administered \>28 days prior to start of treatment; Prior PARPi therapy, as per local prescribing information, with the last dose administered \>14 days prior to start of treatment; One prior RLT or radiotherapeutic agent (e.g., PSMA-targeted RLT, Radium 223) with the last dose administered \>8 weeks prior to start of treatment
* Other concurrent anti-cancer therapy except for androgen deprivation therapy
* Treatment with strong CYP2C8 inhibitors, strong or moderate CYP2C8 inducers, or strong CYP3A4 inducers within 1 week or 5 drug-elimination half-lives, whichever is longer, prior to initiation of study treatment
* Transfusion of any blood product for the sole purpose of making a potential participant eligible for study inclusion or within 28 days of enrollment
→
Inclusion Criteria:
* Histologically or cytologically confirmed adenocarcinoma of the prostate without small-cell or neuroendocrine features
* Progressive metastatic CRPC, defined as any of the following: PSA progression, defined by a minimum of two rising PSA values from three consecutive assessments with an interval of at least 7 days between assessments and with a minimal starting value of PSA \>=1 ng/mL; The most recent qualifying PSA value must be determined within 14 days of enrollment; Soft tissue disease progression, defined by Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1); Bone disease progression, defined by PCWG3 criteria, with two or more new metastatic bone lesions on a whole-body radionuclide bone scan
* Treatment with at least one, but no more than one, prior second-generation ARPi (abiraterone, apalutamide, enzalutamide, darolutamide) for at least 12 weeks for HSPC or CRPC
* Availability of a tumor tissue specimen that is suitable (e.g., adequate quality and quantity) for use in determining biomarker status
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
* Fasting glucose \<126 mg/dL and HbA1c \< 6%
Exclusion Criteria:
* Presence of liver metastasis
* Prior treatment with any phosphatidylinositol-3-kinase (PI3K), protein kinase B (AKT), or mammalian target of rapamycin (mTOR) inhibitor, or with any agent with a mechanism of action of inhibiting the PI3K/AKT/mTOR pathway
* Type 1 or Type 2 diabetes mellitus
* Prior treatment for mCRPC with cytotoxic chemotherapy or novel hormonal treatments (e.g., androgen receptor degraders, CYP11 inhibitors), with the following treatments permitted: Prior docetaxel in mHSPC, providing no evidence of disease progression occurred during treatment or within 6 months of treatment completion; Prior docetaxel in the adjuvant or neoadjuvant setting providing no evidence of disease progression occurred during treatment or within 12 months of treatment completion; Prior treatment with sipuleucel-T, with the last dose administered \>28 days prior to start of treatment; Prior PARPi therapy, as per local prescribing information, with the last dose administered \>14 days prior to start of treatment; One prior RLT or radiotherapeutic agent (e.g., PSMA-targeted RLT, Radium 223) with the last dose administered \>8 weeks prior to start of treatment
* Other concurrent anti-cancer therapy except for androgen deprivation therapy
* Treatment with strong CYP2C8 inhibitors, strong or moderate CYP2C8 inducers, or strong CYP3A4 inducers within 1 week or 5 drug-elimination half-lives, whichever is longer, prior to initiation of study treatment
* Transfusion of any blood product for the sole purpose of making a potential participant eligible for study inclusion or within 28 days of enrollment
Inclusion Criteria:
* Children and adolescents from 10 years to less than 18 years of age, at the time of baseline visit
* Body weight ≥25 kg
* Diagnosis of RRMS in accordance with the International Pediatric Multiple Sclerosis Study Group (IPMSSG) criteria for pediatric MS, Version 2012, or McDonald criteria 2017 or 2024
* Neurologic stability for at least 30 days prior to screening, and between screening and baseline
* Expanded Disability Status Scale (EDSS) score, 0-5.5, at screening
* Must have received all childhood required vaccinations as per local/national recommendations for childhood vaccination against infectious diseases
Exclusion Criteria:
* Participants who are positive for aquaporin 4 (AQP4) or myelin oligodendrocyte glycoprotein (MOG) antibody are not eligible to participate in the study
* Any known presence or suspicion of other neurologic disorders that may mimic multiple sclerosis (MS)
* History or known presence of recurrent or chronic infection (e.g., human immunodeficiency virus \[HIV\], syphilis, tuberculosis \[TB\])
* Contraindications against SC injections or other conditions not suitable for SC injections, e.g., extremely thin SC fat layer
* History of a severe allergic or anaphylactic reaction to humanized or murine monoclonal antibody or known hypersensitivity to any component of ocrelizumab solution
* Contraindications to mandatory premedications (i.e., corticosteroids and histamines), including closed-angle glaucoma for antihistamines
* Participants who have previously received treatment with B cell-targeted therapies, including ocrelizumab
* Any previous treatment with alemtuzumab, anti-CD4, cladribine, mitoxantrone, daclizumab, laquinimod, total body irradiation, or bone marrow transplantation
* Treatment with any investigational agent within 24 weeks of screening or 5 half-lives, whichever is longer (or longer if indicated by the PD action of the drug)
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Inclusion Criteria:
* Children and adolescents from 10 years to less than 18 years of age, at the time of baseline visit
* Body weight ≥25 kg
* Diagnosis of RRMS in accordance with the International Pediatric Multiple Sclerosis Study Group (IPMSSG) criteria for pediatric MS, Version 2012, or McDonald criteria 2017 or 2024
* Neurologic stability for at least 30 days prior to screening, and between screening and baseline
* Expanded Disability Status Scale (EDSS) score, 0-5.5, at screening
* Must have received all childhood required vaccinations as per local/national recommendations for childhood vaccination against infectious diseases
Exclusion Criteria:
* Participants who are positive for aquaporin 4 (AQP4) or myelin oligodendrocyte glycoprotein (MOG) antibody are not eligible to participate in the study
* Any known presence or suspicion of other neurologic disorders that may mimic multiple sclerosis (MS)
* Any known or suspected active infection at screening or baseline (except nailbed infections), or any major episode of infection requiring hospitalization or treatment with IV anti-infective agents within 4 weeks prior to baseline visit or oral anti-infective agents within 2 weeks prior to baseline visit
* History or known presence of recurrent or chronic infection (e.g., human immunodeficiency virus \[HIV\], syphilis, tuberculosis \[TB\])
* Contraindications against SC injections or other conditions not suitable for SC injections, e.g., extremely thin SC fat layer
* History of a severe allergic or anaphylactic reaction to humanized or murine monoclonal antibody or known hypersensitivity to any component of ocrelizumab solution
* Contraindications to mandatory premedications (i.e., corticosteroids and histamines), including closed-angle glaucoma for antihistamines
* Participants who have previously received treatment with B cell-targeted therapies, including ocrelizumab
* Any previous treatment with cyclophosphamide, alemtuzumab, anti-CD4, cladribine, mitoxantrone, daclizumab, laquinimod, total body irradiation, or bone marrow transplantation
* Treatment with any investigational agent within 24 weeks of screening or 5 half-lives, whichever is longer (or longer if indicated by the PD action of the drug)