Inclusion Criteria:
* At any time prior to the Screening Visit, participant must have been treated for \> or = 3 months with at least 1 b/tsDMARD therapy but continued to exhibit active RA, or had to discontinue due to intolerability or toxicity, irrespective of treatment duration. The maximum cap for prior use of b/tsDMARD is 2.
* Participant must be on a stable dose of methotrexate (MTX)
Exclusion Criteria:
* Participant is taking nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen/paracetamol, low-potency opioids (tramadol, codeine, hydrocodone, alone or in combination with acetaminophen), oral corticosteroids (equivalent to ≤ 10 mg/day of prednisone), or inhaled corticosteroids for stable medical conditions unless they have been on stable doses for ≥ 1 week prior to Baseline Visit.
* History of any arthritis with onset prior to age 17 years or current diagnosis of inflammatory joint disease other than rheumatoid arthritis.
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Inclusion Criteria:
* At any time prior to the Screening Visit, participant must have been treated for \> or = 3 months with at least 1 b/tsDMARD therapy but continued to exhibit active RA, or had to discontinue due to intolerability or toxicity, irrespective of treatment duration. The maximum cap for prior use of b/tsDMARD is 2.
* Participant must be on a stable dose of methotrexate (MTX)
Exclusion Criteria:
* Participant is taking nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen/paracetamol, low-potency opioids (tramadol, codeine, hydrocodone, alone or in combination with acetaminophen), oral corticosteroids (equivalent to ≤ 10 mg/day of prednisone), or inhaled corticosteroids for stable medical conditions unless they have been on stable doses for ≥ 1 week prior to Baseline Visit.
* History of any arthritis with onset prior to age 17 years or current diagnosis of inflammatory joint disease other than rheumatoid arthritis.
Sub-study 6 specific:
* Prior exposure to any Interleukin-1 receptor-associated kinase 4 (IRAK4) inhibitor or degrader.
* Prior exposure to any biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs).
Inclusion Criteria:
* Written informed consent obtained to participate in the study and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information to the sponsor, sites, and relevant study organizations.
* Age ≥ 18 years at the time of consent.
* Karnofsky scale ≥ 50% or Eastern Cooperative Oncology Group (ECOG) ≤ 2.
* Histological evidence of B-cell PTLD (any histologic subtype) following solid organ transplantation; expresses CD20; with or without EBV association.
* Treatment failure of immunosuppression reduction (ISR). NOTE: if ISR was deemed not feasible by treating physician, ISR treatment failure may be waived.
* Treatment failure of rituximab or rituximab plus any concurrent or sequentially administered chemotherapy regimen.
* Measurable disease of \> 1.5 cm in diameter and/or bone marrow involvement.
* Subjects having undergone heart, lung, liver, kidney, pancreas, small intestine transplantation or a combination of the organ transplantations mentioned.
* HIV infection is allowed if viral load is undetectable at time of enrollment, CD4+ count \> 200 cells/uL, and subject remains on anti-viral therapy.
* Resolution of toxicities from prior therapy to a grade that does not contraindicate trial participation in the opinion of the investigator.
* Expected survival greater than 60 days.
* Absolute neutrophil count 1.0 ≥ x 10\^9/L.
* Platelets 50 ≥ x 10\^9/L.
* Creatinine clearance (mL/min) ≥ 30 mL/min - Cockcroft-Gault Equation.
* Note: Hematology and other lab parameters that are ≤ grade 2 BUT still meet criteria for study entry are allowed. Furthermore, changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy.
* Bilirubin ≤ 3.0 x upper limit of normal (ULN). Subjects with Gilbert's syndrome may be enrolled despite a total bilirubin level \> 3.0 mg/dL if their conjugated bilirubin is ≤ 3.0 × ULN).
* Note: Hematology and other lab parameters that are ≤ grade 2 BUT still meet criteria for study entry are allowed. Furthermore, changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy.
* Aspartate aminotransferase (AST) ≤ 3.0 x ULN.
* Note: Hematology and other lab parameters that are ≤ grade 2 BUT still meet criteria for study entry are allowed. Furthermore, changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy.
* Alanine aminotransferase (ALT) ≤ 3.0 x ULN.
* Note: Hematology and other lab parameters that are ≤ grade 2 BUT still meet criteria for study entry are allowed. Furthermore, changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy.
* Females of childbearing potential must have a negative serum pregnancy test within 3 days prior to registration. NOTE: Females are considered of childbearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months. Documentation of postmenopausal status must be provided.
* Females of childbearing potential must be willing to abstain from heterosexual activity or to use 2 forms of effective methods of contraception from the time of informed consent until 12 months after treatment the last dose of epcoritamab. The two contraception methods can be comprised of two barrier methods, or a barrier method plus a hormonal method or an intrauterine device.
* Male subjects with female partners must have had a prior vasectomy or agree to use an adequate method of contraception (i.e., double barrier method: condom plus spermicidal agent) starting with the first dose of study therapy through 12 months after the last dose of epcoritamab.
* Subjects with prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the experimental regimen are eligible for the trial.
* Subject is willing and able to comply with study procedures based on the judgement of the investigator or protocol designee.
Exclusion Criteria:
* Uncontrolled active (symptomatic) infection. Patients requiring systemic therapy are eligible if the infection is deemed controlled by the investigator.
* Post-transplant lymphoproliferative disorder following stem cell transplantation for hematologic malignancies or nonmalignant conditions.
* Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study and lactating females must agree to not breastfeed while taking study drug).
* Subjects with central nervous system (CNS) involvement by PTLD.
* Seizure disorder requiring therapy (such as steroids or anti-epileptics).
* Uncontrolled concomitant illness including, but not limited to, symptomatic congestive heart failure (New York Heart Association (NYHA) Class III or IV), unstable angina pectoris, myocardial infarction within 1 month prior to enrollment, uncontrolled cardiac arrhythmias, uncontrolled seizures, or severe non-compensated hypertension (systolic blood pressure \> 180mmHg or diastolic blood pressure \> 120mmHg).
* History of progressive multifocal leukoencephalopathy.
* Active Hepatitis B infection or Hepatitis C infection with positive viral polymerase chain reaction (PCR) from the blood. Subjects with active Hepatitis B infection and undetectable viral PCR from the blood will be allowed with concurrent use of entecavir suppression. Subjects with history of Hepatitis C infection (undetectable viral PCR) are allowed.
* Electrocardiogram (ECG) abnormality at screening has to be documented by the investigator as not medically relevant.
* Any condition, including the presence of laboratory values which is deemed by the clinician to place the subject at an unacceptable risk or confounds the ability to interpret the data from this study.
* Live virus vaccines must not be administered within 28 days of the start of study treatment.
* Any investigational treatments must have been completed at least 4 weeks or 5 half-lives, whichever is shorter, prior to the start of study treatment. Investigational antibody therapies are not included in this requirement.
→
Inclusion Criteria:
* Written informed consent obtained to participate in the study and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information to the sponsor, sites, and relevant study organizations.
* Age ≥ 18 years at the time of consent.
* Karnofsky scale ≥ 50% or Eastern Cooperative Oncology Group (ECOG) ≤ 2.
* Histological evidence of B-cell PTLD (any histologic subtype) following solid organ transplantation; expresses CD20; with or without EBV association.
* Subjects are eligible with prior immunosuppression reduction (ISR) or the absence of prior ISR.
* Treatment failure of rituximab or rituximab plus any concurrent or sequentially administered chemotherapy regimen.
* Measurable disease of \> 1.5 cm in diameter and/or bone marrow involvement.
* Subjects having undergone heart, lung, liver, kidney, pancreas, small intestine transplantation or a combination of the organ transplantations mentioned.
* HIV infection is allowed if viral load is undetectable at time of enrollment, CD4+ count \> 200 cells/uL, and subject remains on anti-viral therapy.
* Resolution of toxicities from prior therapy to a grade that does not contraindicate trial participation in the opinion of the investigator.
* Expected survival greater than 60 days.
* Absolute neutrophil count 1.0 ≥ x 10\^9/L.
* Platelets 50 ≥ x 10\^9/L.
* Creatinine clearance (mL/min) ≥ 30 mL/min - Cockcroft-Gault Equation.
* Note: Hematology and other lab parameters that are \> grade 2 BUT still meet criteria for study entry are allowed. Furthermore, changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy.
* Bilirubin ≤ 3.0 x upper limit of normal (ULN). Subjects with Gilbert's syndrome may be enrolled despite a total bilirubin level \> 3.0 mg/dL if their conjugated bilirubin is ≤ 3.0 × ULN).
* Note: Hematology and other lab parameters that are ≤ grade 2 BUT still meet criteria for study entry are allowed. Furthermore, changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy.
* Aspartate aminotransferase (AST) ≤ 3.0 x ULN.
* Note: Hematology and other lab parameters that are \> grade 2 BUT still meet criteria for study entry are allowed. Furthermore, changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy.
* Alanine aminotransferase (ALT) ≤ 3.0 x ULN.
* Note: Hematology and other lab parameters that are \> grade 2 BUT still meet criteria for study entry are allowed. Furthermore, changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy.
* Females of childbearing potential must have a negative serum pregnancy test within 3 days prior to registration. NOTE: Females are considered of childbearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months. Documentation of postmenopausal status must be provided.
* Females of childbearing potential must be willing to abstain from heterosexual activity or to use 2 forms of effective methods of contraception from the time of informed consent until 12 months after treatment the last dose of epcoritamab. The two contraception methods can be comprised of two barrier methods, or a barrier method plus a hormonal method or an intrauterine device.
* Male subjects with female partners must have had a prior vasectomy or agree to use an adequate method of contraception (i.e., double barrier method: condom plus spermicidal agent) starting with the first dose of study therapy through 12 months after the last dose of epcoritamab.
* Subjects with prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the experimental regimen are eligible for the trial.
* Subject is willing and able to comply with study procedures based on the judgement of the investigator or protocol designee.
Exclusion Criteria:
* Uncontrolled active (symptomatic) infection. Patients requiring systemic therapy are eligible if the infection is deemed controlled by the investigator.
* Post-transplant lymphoproliferative disorder following stem cell transplantation for hematologic malignancies or nonmalignant conditions.
* Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study and lactating females must agree to not breastfeed while taking study drug).
* Subjects with central nervous system (CNS) involvement by PTLD.
* Seizure disorder requiring therapy (such as steroids or anti-epileptics).
* Uncontrolled concomitant illness including, but not limited to, symptomatic congestive heart failure (New York Heart Association (NYHA) Class III or IV), unstable angina pectoris, myocardial infarction within 1 month prior to enrollment, uncontrolled cardiac arrhythmias, uncontrolled seizures, or severe non-compensated hypertension (systolic blood pressure \> 180mmHg or diastolic blood pressure \> 120mmHg).
* History of progressive multifocal leukoencephalopathy.
* Active Hepatitis B infection or Hepatitis C infection with positive viral polymerase chain reaction (PCR) from the blood. Subjects with active Hepatitis B infection and undetectable viral PCR from the blood will be allowed with concurrent use of entecavir suppression. Subjects with history of Hepatitis C infection (undetectable viral PCR) are allowed.
* Any condition, including the presence of laboratory values which is deemed by the clinician to place the subject at an unacceptable risk or confounds the ability to interpret the data from this study.
* Live virus vaccines must not be administered within 28 days of the start of study treatment.
* Any investigational treatments must have been completed at least 4 weeks or 5 half-lives, whichever is shorter, prior to the start of study treatment. Investigational antibody therapies are not included in this requirement.
Inclusion Criteria:
* Participants' body weight must be \>= 40 kg at Baseline.
* Confirmed diagnosis of CD for at least 3 months prior to Baseline. Documentation of biopsy results consistent with the diagnosis of CD as assessed by the Investigator must be available.
* CDAI \>= 220 at Baseline.
* Endoscopic evidence of mucosal inflammation as documented by an SES-CD of \>= 6 for ileocolonic or colonic disease or SES-CD of \>= 4 for isolated ileal disease. All eligible scores exclude the presence of narrowing component and are determined by a reader.
* Participants must demonstrate intolerance or inadequate response to conventional therapies (OUS) and/or TaTs. TaTs include biologics and/or targeted small molecules.
Exclusion Criteria:
* Participant who demonstrated intolerance to p19 inhibitors, including risankizumab.
* Participant who received any investigational TaT (or TaT that becomes approved during the conduct of the study) within 30 days or 5 half-lives prior to Baseline, whichever is longer. Note: If there is documentation of an undetectable (or below the lower limit of quantification/quantitation) drug level measured by a commercially available assay for any of the approved biologics above, there is no minimum washout prior to Baseline.
* Participant who have any of the following: Current diagnosis of UC or indeterminate colitis. Currently known complications of CD such as: Current ostomy or ileoanal pouch; Current short gut or short bowel syndrome; Surgical bowel resection within the past 3 months prior to Baseline.
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Inclusion Criteria:
* Participants' body weight must be \>= 40 kg at Baseline.
* Confirmed diagnosis of CD for at least 3 months prior to Baseline. Documentation of biopsy results consistent with the diagnosis of CD as assessed by the Investigator must be available.
* CDAI \>= 220 at Baseline.
* Endoscopic evidence of mucosal inflammation as documented by an SES-CD of \>= 6 for ileocolonic or colonic disease or SES-CD of \>= 4 for isolated ileal disease. All eligible scores exclude the presence of narrowing component and are determined by a reader.
* Participants must demonstrate intolerance or inadequate response to conventional therapies (OUS) and/or TaTs. TaTs include biologics and/or targeted small molecules.
Exclusion Criteria:
* Participant with history of intolerance to p19 inhibitors, including risankizumab.
* Participant who have any of the following: Current diagnosis of UC or indeterminate colitis. Currently known complications of CD such as: Current ostomy or ileoanal pouch; Current short gut or short bowel syndrome; Surgical bowel resection within the past 3 months prior to Baseline.
Inclusion Criteria:
* Diagnosis of an advanced or unresectable malignant high grade serous epithelial ovarian, fallopian tube, and primary peritoneal cancers (EOC), fallopian tube or primary peritoneal cancer by histology (World Health Organization \[WHO\] criteria).
* Participants must be considered platinum resistant or platinum ineligible. Platinum resistant disease is defined as radiographic progression within 6 months (up to 182 days) after the last dose of the most recent platinum therapy).
* Prior anticancer therapy:
* Must have received appropriate standard of care therapy and be appropriate for participation in a Phase I study in the opinion of the investigator.
* Platinum-resistant, high grade serous EOC cannot have had more than 2 prior lines of therapy, since the development of platinum resistance or ineligibility.
* For participants enrolled in backfill, subjects must provide consent to paired biopsies which are pretreatment and on-treatment tumor biopsies from the same tumor lesion.
Exclusion Criteria:
* Ovarian Cancer (OC) with histologies other than high grade serous OC including endometrioid, low grade, clear cell, mucinous, or borderline ovarian tumor.
* Prior therapy with an antibody-drug conjugate containing a topoisomerase inhibitor.
* Prior history of Grade \>= 2 ILD or pneumonitis.
* History of interstitial lung disease (ILD) or pneumonitis that required treatment with systemic steroids, or any evidence of active ILD or pneumonitis on Screening chest computed tomography (CT) scan.
* Must not have systemically used known strong cytochrome P450 (CYP)3A inhibitors or inducers within 14 days or 5 half-lives of the drug (whichever is shorter) prior to the first dose of the study drug through the end of the DLT observation period. If clinically indicated, strong CYP3A inhibitors and inducers may be used with caution after the dose-limiting toxicity (DLT) period.
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Inclusion Criteria:
* Diagnosis of an advanced or unresectable malignant high grade serous epithelial ovarian, fallopian tube, and primary peritoneal cancers (EOC), fallopian tube or primary peritoneal cancer by histology (World Health Organization \[WHO\] criteria).
* Participants enrolled in backfill (Part 1) must provide consent to paired fresh biopsies which are pretreatment and on-treatment tumor biopsies from the same tumor lesion.
For Parts 1-4:
\- Participants must be considered platinum resistant or platinum ineligible. Platinum resistant disease is defined as radiographic progression within 6 months (up to 182 days) after the last dose of the most recent platinum therapy).
For Parts 5-6:
\- Participants will have platinum-sensitive disease defined as radiographic progression \> 6 months from last dose of platinum-based chemotherapy. Note: Progression should be calculated from the date of the last administered dose of platinum therapy to the date of the radiographic imaging showing progression.
Exclusion Criteria:
* Ovarian Cancer (OC) with histologies other than high grade serous OC including endometrioid, low grade, mucinous, carcinosarcoma or sarcomatous histology, mixed tumors or low grade/borderline ovarian tumor.
* Participants with platinum refractory disease.
* Prior therapy with an antibody-drug conjugate containing a topoisomerase inhibitor.
* Prior history of Grade \>= 2 interstitial lung disease (ILD) or pneumonitis.
* Prior history of Grade 2 \>= 2 ILD or pneumonitis or any evidence of active ILD or pneumonitis on Screening chest computed tomography (CT) scan.
For Parts 3-6:
* History of Grade 3/4 adverse events that, in the opinion of the investigator, are attributed to bevacizumab.
* History of clinically significant cardiac disease including CHF Class II or higher NYHA; active coronary artery disease, MI within 6 months prior to study entry; unevaluated new onset angina within 3 months or unstable angina (angina symptoms at rest) or cardiac arrhythmias requiring antiarrhythmic therapy (beta blockers or digoxin are permitted).
* Echocardiogram with ejection fraction \<= 50% and no other clinically significant cardiac abnormalities that in the opinion of the investigator, would increase the participants susceptibility to cardiac toxicity.
For Parts 5-6:
\- Participants who had prior allergic reaction to platinum containing compound.
Inclusion Criteria:
* Participants with a diagnosis of levodopa-responsive idiopathic Parkinson's disease
* Eligibility for foscarbidopa/foslevodopa (LDp/CDp) therapy in accordance with the approved local label
* Participant must be an adult male or female, 18-64 years of age
* Time since beginning of motor fluctuations ≤ 3 years
* The Hoehn and Yahr (H\&Y) stage \< 3 in the on-medication condition
* Decision to treat with LDp/CDp made by the clinician prior to any decision to approach the participant to participate in this study
Exclusion Criteria:
* Previous Exposure to any device-aided therapy (DAT).
* Any condition included in the contraindications section of the approved local LDp/CDp label.
* Participants with Mini mental state examination (MMSE) score \< 24
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Inclusion Criteria:
* Participants with a diagnosis of levodopa-responsive idiopathic Parkinson's disease
* Eligibility for foscarbidopa/foslevodopa (LDp/CDp) therapy in accordance with the approved local label
* Participant must be an adult male or female, 18-67 years of age
* Time since beginning of motor fluctuations \<= 5 years
* The Hoehn and Yahr (H\&Y) stage \<= 3
* Decision to treat with LDp/CDp made by the clinician prior to any decision to approach the participant to participate in this study
Exclusion Criteria:
* Previous Exposure to any device-aided therapy (DAT).
* Any condition included in the contraindications section of the approved local LDp/CDp label.
* Participants with Mini mental state examination (MMSE) score \< 24
Inclusion Criteria:
* At any time prior to the Screening Visit, participant must have been treated for \> or = 3 months with at least 1 b/tsDMARD therapy but continued to exhibit active RA, or had to discontinue due to intolerability or toxicity, irrespective of treatment duration. The maximum cap for prior use of b/tsDMARD is 2.
* Participant must be on a stable dose of methotrexate (MTX)
Exclusion Criteria:
* Participant is taking nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen/paracetamol, low-potency opioids (tramadol, codeine, hydrocodone, alone or in combination with acetaminophen), oral corticosteroids (equivalent to ≤ 10 mg/day of prednisone), or inhaled corticosteroids for stable medical conditions unless they have been on stable doses for ≥ 1 week prior to Baseline Visit.
* History of any arthritis with onset prior to age 17 years or current diagnosis of inflammatory joint disease other than rheumatoid arthritis.
Sub-study 6 specific:
* Prior exposure to any Interleukin-1 receptor-associated kinase 4 (IRAK4) inhibitor or degrader.
* Prior exposure to any biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs).
→
Inclusion Criteria:
* At any time prior to the Screening Visit, participant must have been treated for \> or = 3 months with at least 1 b/tsDMARD therapy but continued to exhibit active RA, or had to discontinue due to intolerability or toxicity, irrespective of treatment duration. The maximum cap for prior use of b/tsDMARD is 2.
* Participant must be on a stable dose of methotrexate (MTX)
Exclusion Criteria:
* Participant is taking nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen/paracetamol, low-potency opioids (tramadol, codeine, hydrocodone, alone or in combination with acetaminophen), oral corticosteroids (equivalent to ≤ 10 mg/day of prednisone), or inhaled corticosteroids for stable medical conditions unless they have been on stable doses for ≥ 1 week prior to Baseline Visit.
* History of any arthritis with onset prior to age 17 years or current diagnosis of inflammatory joint disease other than rheumatoid arthritis.
Inclusion Criteria:
* 18 to 70 years of age
* Weight ≥ 40 kg and BMI ≥ 18.0 kg/m2.
* History of migraine headaches with or without aura, with migraine onset at ≤ 50 years of age and for at least 12 months prior to screening.
* At least 12 MHDs over the last 3 months prior to screening.
* Participants must fulfil the following criteria for migraine in prospectively collected baseline information during the 4 consecutive weeks of baseline migraine headache data collection prior to Day 1: (a) ≥ 4 and ≤ 14 MHDs per month. (b) On ≥ 4 days, fulfils any of the following criteria: (i) migraine without aura; (ii) migraine with an aura symptom accompanied or followed by a headache within 60 minutes; (iii) probable migraine; (iv) recurrent attacks that do not match ICHD criteria for migraine but successfully respond to migraine-specific medication.
* Participants who fulfil criteria for MOH are eligible for this study.
* History of unsuccessful treatment with ≥ 2 small molecule migraine preventive treatments from different classes (a) aCGRP-N participants are eligible to receive an aCGRP therapy but must have not yet received aCGRP therapy for acute or preventive treatment at any time. (b) aCGRP-IR participants must have tried and have failed at least one aCGRP therapy used for preventive treatment.
* Participants must be able to distinguish migraine headaches from tension-type headaches.
* Female participants who are not pregnant and do not plan to become pregnant during the study, are not lactating, or are of nonchildbearing potential. FOCBP who are sexually active with a non-sterilised male partner must use adequate contraception consisting of two highly effective methods of contraception throughout the study. FOCBP must agree to comply with protocol specified guidance for safe administration of MEDI0618. FOCBP must refrain from egg donation and in vitro fertilisation from the time of signing the ICF, throughout the study, and for 10 weeks after the last administration of investigational product (IP).
Exclusion Criteria:
* History of migraine sub-types including hemiplegic (sporadic or familial) migraine, ophthalmoplegic migraine, and basilar-type migraine
* History of headache other than migraine within 3 months prior to screening.
* History of severe or ongoing allergy/hypersensitivity reactions or history of hypersensitivity to immunisations or immunoglobulins.
* History of any significant psychiatric disorder which could be detrimental to participant safety or could compromise study data interpretation.
* Presence of any clinically significant illness, such as cardiovascular, neurologic (except for non-exclusionary headaches in participants with migraine), pulmonary, hepatic, renal, metabolic, gastrointestinal, urologic, immunologic, or endocrine disease or disorder.
* History of cancer within 5 years of screening, or between screening and randomisation, with the exception of non-metastatic basal cell carcinoma of the skin, carcinoma in situ of the cervix, or non-progressive prostate cancer.
* Known history of drug or alcohol abuse within 1 year of screening or positive test for drugs of abuse or alcohol at screening or at Day -1.
* History of QT prolongation \> 450 msec (\> 470 msec for participants aged ≥ 65 years) associated with other medications that required discontinuation of that medication.
* Congenital long or short QT syndrome.
* History of arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia), which is symptomatic or requires treatment, symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Participants with atrial fibrillation controlled by medication are permitted.
* Use of migraine preventive medications within 30 days or 5 half-lives (whichever is longer) prior to screening and throughout the study
* For aCGRP-N participants only: prior use of an aCGRP therapy for acute or preventive treatment.
* Use of opioids or barbiturate containing analgesic \> 2 times/month on average in the 6 months prior to screening for the treatment of pain (opioid administration in an emergency setting may be an exception).
* Use of botulinum toxin (e.g., Botox ®, Dysport®, Jeuveau™, Myobloc®, Xeomin®) for migraine or for any other medical or cosmetic reasons requiring injections in the head, face, or neck during the 4 months prior to screening.
* Use of an intervention or device (eg, scheduled nerve block, transcranial magnetic stimulation) for treatment of migraine within 2 months of screening.
* Use of prescription or non-prescription, non-biologic drugs, including vitamins and herbal and dietary supplements, within 7 days or 5 half-lives (whichever is longer) prior to screening and throughout the study unless the medication will not interfere with the study procedures or compromise participant safety; the dose and regimen must have been stable for at least 3 months prior to screening and must remain stable throughout the study.
* Requires treatment with another biological therapeutic agent including IV immunoglobulin treatment during the course of the study. Prior use of therapeutic antibodies is allowed if that use was \> 5 half-lives of the intervention or 3 months prior to screening, whichever is longer.
* Therapeutic vaccines are permitted during the study, but ideally, live attenuated vaccines should be administered \> 30 days prior to randomisation and inactivated vaccinations (eg, inactive influenza, COVID-19) should be administered \> 14 days prior to randomisation.
* Participation in another clinical study with an IP, including an experimental vaccine, or device, within 5 half-lives of the intervention or 3 months prior to screening, whichever is longer.
* Known hypersensitivity to MEDI0618 or any of the excipients of the product.
Other protocol defined inclusion and exclusion criteria may apply.
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Inclusion Criteria:
* 18 to 70 years of age
* Weight ≥ 40 kg and BMI ≥ 18.0 kg/m2.
* History of migraine headaches with or without aura, with migraine onset at ≤ 50 years of age and for at least 12 months prior to screening.
* At least 12 MHDs over the last 3 months prior to screening.
* Participants must fulfil the following criteria for migraine in prospectively collected baseline information during the 4 consecutive weeks of baseline migraine headache data collection prior to Day 1: (a) ≥ 4 and ≤ 14 MHDs per month. (b) On ≥ 4 days, fulfils any of the following criteria: (i) migraine without aura; (ii) migraine with an aura symptom accompanied or followed by a headache within 60 minutes; (iii) probable migraine; (iv) recurrent attacks that do not match ICHD criteria for migraine but successfully respond to migraine-specific medication.
* Participants who fulfil criteria for MOH are eligible for this study.
* History of unsuccessful treatment with ≥ 2 small molecule migraine preventive treatments from different classes (a) aCGRP-N participants are eligible to receive an aCGRP therapy but must have not yet received aCGRP therapy for acute or preventive treatment at any time. (b) aCGRP-IR participants must have tried and have failed at least one aCGRP therapy used for preventive treatment.
* Participants must be able to distinguish migraine headaches from tension-type headaches.
* Female participants who are not pregnant and do not plan to become pregnant during the study, are not lactating, or are of nonchildbearing potential. FOCBP who are sexually active with a non-sterilised male partner must use adequate contraception consisting of one highly effective methods of contraception throughout the study. FOCBP must agree to comply with protocol specified guidance for safe administration of MEDI0618. FOCBP must refrain from egg donation and in vitro fertilisation from the time of signing the ICF, throughout the study, and for 10 weeks after the last administration of investigational product (IP).
Exclusion Criteria:
* History of migraine sub-types including hemiplegic (sporadic or familial) migraine, ophthalmoplegic migraine, and basilar-type migraine
* History of headache other than migraine within 3 months prior to screening.
* History of severe or ongoing allergy/hypersensitivity reactions or history of hypersensitivity to immunisations or immunoglobulins.
* History of any significant psychiatric disorder which could be detrimental to participant safety or could compromise study data interpretation.
* Presence of any clinically significant illness, such as cardiovascular, neurologic (except for non-exclusionary headaches in participants with migraine), pulmonary, hepatic, renal, metabolic, gastrointestinal, urologic, immunologic, or endocrine disease or disorder.
* History of cancer within 5 years of screening, or between screening and randomisation, with the exception of non-metastatic basal cell carcinoma of the skin, carcinoma in situ of the cervix, or non-progressive prostate cancer.
* Known history of drug or alcohol abuse within 1 year of screening or positive test for drugs of abuse or alcohol at screening or at Day -1.
* History of QT prolongation \> 450 msec (\> 470 msec for participants aged ≥ 65 years) associated with other medications that required discontinuation of that medication.
* Congenital long or short QT syndrome.
* History of arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia), which is symptomatic or requires treatment, symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Participants with atrial fibrillation controlled by medication are permitted.
* Use of migraine preventive medications within 30 days or 5 half-lives (whichever is longer) prior to screening and throughout the study
* For aCGRP-N participants only: prior use of an aCGRP therapy for acute or preventive treatment.
* Use of opioids or barbiturate containing analgesic \> 2 times/month on average in the 6 months prior to screening for the treatment of pain (opioid administration in an emergency setting may be an exception).
* Use of botulinum toxin (e.g., Botox ®, Dysport®, Jeuveau™, Myobloc®, Xeomin®) for migraine or for any other medical or cosmetic reasons requiring injections in the head, face, or neck during the 4 months prior to screening.
* Use of an intervention or device (eg, scheduled nerve block, transcranial magnetic stimulation) for treatment of migraine within 2 months of screening.
* Use of prescription or non-prescription, non-biologic drugs, including vitamins and herbal and dietary supplements, within 7 days or 5 half-lives (whichever is longer) prior to screening and throughout the study unless the medication will not interfere with the study procedures or compromise participant safety; the dose and regimen must have been stable for at least 3 months prior to screening and must remain stable throughout the study.
* Requires treatment with another biological therapeutic agent including IV immunoglobulin treatment during the course of the study. Prior use of therapeutic antibodies is allowed if that use was \> 5 half-lives of the intervention or 3 months prior to screening, whichever is longer.
* Therapeutic vaccines are permitted during the study, but ideally, live attenuated vaccines should be administered \> 30 days prior to randomisation and inactivated vaccinations (eg, inactive influenza, COVID-19) should be administered \> 14 days prior to randomisation.
* Participation in another clinical study with an IP, including an experimental vaccine, or device, within 5 half-lives of the intervention or 3 months prior to screening, whichever is longer.
* Known hypersensitivity to MEDI0618 or any of the excipients of the product.
Other protocol defined inclusion and exclusion criteria may apply.