Inclusion Criteria:
* Patients with unresectable or metastatic disease who are refractory to or are not candidates for standard approved therapy
* Histologic confirmation of malignancy
* Measurable disease per RECIST v1.1
* Eastern Cooperative Oncology Group Performance Status (ECOG) of 0 or 1
* Participants must have adequate organ function as defined by laboratory tests
* Part 1: Following tumor types: Breast cancer, cervical cancer, colorectal cancer, adenocarcinoma or squamous cell carcinoma of the esophagus, gastric or gastroesophageal junction adenocarcinoma, squamous cell carcinoma of the head and neck, hepatobiliary cancers (hepatocellular carcinoma (HCC), gallbladder cancer, cholangiocarcinoma), non-small cell lung cancer, renal cell carcinoma, squamous cell carcinoma of the skin, pancreatic adenocarcinoma, ovarian cancer or urothelial carcinoma
* Part 2: Following tumor types: Squamous cell carcinoma of the head and neck, Gastric or gastroesophageal junction adenocarcinoma, non-squamous non-small cell lung cancer, non-small cell lung cancer, colorectal carcinoma (CRC) any RAS, and/or Cholangiocarcinoma
Exclusion Criteria:
* Active, known or suspected autoimmune disease
* Condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications
* Brain or leptomeningeal metastases
* Known history of positive test for HIV
* Non-HCC patients: acute or chronic hepatitis B virus (HBV) or hepatitis C virus (HCV); HCC patients: untreated active HBV or dual infection with HBV/HCV
* Participants after solid organ or allogeneic hematopoietic stem cell transplant
* History of life-threatening toxicity related to prior immune therapy
* History of life-threatening toxicity related to prior cetuximab or other anti-EGFR antibodies (for Sub-Part 1C)
* Unstable or deteriorating cardiovascular disease within the previous 6 months
* Any major surgery within 4 weeks of study drug administration
* Prior/Concomitant Therapy:
* Cytotoxic/Non-cytotoxic anti-cancer agents, unless at least 4 weeks have elapsed from last dose
* Use of other investigational drugs within 28 days
* Prior treatment with macrophage or natural killer (NK) cells activating therapies
* Administration of a live attenuated vaccine within 28 days
The above information is not intended to contain all considerations relevant to the potential participation in a clinical trial.
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Inclusion Criteria:
* Participants with unresectable or metastatic disease who were refractory to or were not candidates for standard approved therapy
* Histologic confirmation of malignancy
* Measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
* Eastern Cooperative Oncology Group Performance Status (ECOG) of 0 or 1
* Participants must be with adequate organ function as defined by laboratory tests
* Part 1: Following tumor types: Breast cancer, cervical cancer, colorectal cancer, adenocarcinoma or squamous cell carcinoma of the esophagus, gastric or gastroesophageal junction adenocarcinoma, squamous cell carcinoma of the head and neck, hepatobiliary cancers (hepatocellular carcinoma (HCC), gallbladder cancer, cholangiocarcinoma), non-small cell lung cancer, renal cell carcinoma, squamous cell carcinoma of the skin, pancreatic adenocarcinoma, ovarian cancer or urothelial carcinoma
* Part 2: Following tumor types: Squamous cell carcinoma of the head and neck, Gastric or gastroesophageal junction adenocarcinoma, non-squamous non-small cell lung cancer, non-small cell lung cancer, colorectal carcinoma (CRC) any RAS, and/or Cholangiocarcinoma
Exclusion Criteria:
* Active, known or suspected autoimmune disease
* Condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications
* Brain or leptomeningeal metastases
* Known history of positive test for HIV
* Non-HCC participants: acute or chronic hepatitis B virus (HBV) or hepatitis C virus (HCV); HCC participants: untreated active HBV or dual infection with HBV/HCV
* Participants after solid organ or allogeneic hematopoietic stem cell transplant
* History of life-threatening toxicity related to prior immune therapy
* History of life-threatening toxicity related to prior cetuximab or other anti-EGFR antibodies (for Sub-Part 1C)
* Unstable or deteriorating cardiovascular disease within the previous 6 months
* Any major surgery within 4 weeks of study drug administration
* Prior/Concomitant Therapy:
* Cytotoxic/Non-cytotoxic anti-cancer agents, unless at least 4 weeks have elapsed from last dose
* Use of other investigational drugs within 28 days
* Prior treatment with macrophage or natural killer (NK) cells activating therapies
* Administration of a live attenuated vaccine within 28 days
The above information was not intended to contain all considerations relevant to the potential participation in a clinical trial.
Inclusion Criteria:
* Aged ≥18 years;
* Active KPSC member;
* Continuous membership from 27 August 2025 to 27 September 2026;
* Members who are aged 65 years and older, or adults aged 18-64 years with at least one of the following health conditions that increases their risk for severe COVID-19 illness, including: a) asthma, b) cancer, c) ischemic stroke, d) intracerebral or subarachnoid hemorrhage, e) transient ischemic attack, f) chronic kidney disease, g) dialysis, h) bronchiectasis, i) chronic obstructive, pulmonary disease (COPD), j) pulmonary fibrosis, k) cystic fibrosis, l) pulmonary hypertension, m) cirrhosis, n) non-alcoholic fatty liver disease (NALD), o) alcoholic liver disease, p) autoimmune hepatitis, q) diabetes, r) heart failure, s) coronary artery disease, t) cardiomyopathy, u) HIV, v) obesity, w) essential hypertension, x) primary immunodeficiency and other underlying immunocompromising conditions, y) solid organ or blood stem cell transplant, z) tuberculosis;
* No documented receipt of updated 2026-27 COVID-19 vaccine as of 28 September 2026;
* Has valid email information.
Exclusion Criteria:
* Unable to receive or opted out of email communication.
* People who cannot safely receive a COVID-19 vaccine, including those who had a severe allergic reaction to a previous COVID-19 vaccine or have a contraindication to COVID-19 vaccine or a vaccine ingredient, will not be included in the study.
* People who are pregnant or breastfeeding will not be included.
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Inclusion Criteria:
* Aged ≥18 years;
* Active KPSC member;
* Continuous membership from 27 August 2025 to 28 September 2026;
* Members who are aged 65 years and older, or adults aged 18-64 years with at least one of the following health conditions that increases their risk for severe COVID-19 illness, including: a) asthma, b) cancer, c) ischemic stroke, d) intracerebral or subarachnoid hemorrhage, e) transient ischemic attack, f) chronic kidney disease, g) dialysis, h) bronchiectasis, i) chronic obstructive, pulmonary disease (COPD), j) pulmonary fibrosis, k) cystic fibrosis, l) pulmonary hypertension, m) cirrhosis, n) non-alcoholic fatty liver disease (NALD), o) alcoholic liver disease, p) autoimmune hepatitis, q) diabetes, r) heart failure, s) coronary artery disease, t) cardiomyopathy, u) HIV, v) obesity, w) essential hypertension, x) primary immunodeficiency and other underlying immunocompromising conditions, y) solid organ or blood stem cell transplant, z) tuberculosis;
* No documented receipt of updated 2026-27 COVID-19 vaccine as of 28 September 2026;
* Has valid email information.
Exclusion Criteria:
* Unable to receive or opted out of email communication.
* People with unknown or missing sex.
* People who cannot safely receive a COVID-19 vaccine, including those who had a severe allergic reaction to a previous COVID-19 vaccine or have a contraindication to COVID-19 vaccine or a vaccine ingredient, will not be included in the study.
* People with metastatic or terminal illness, advanced illness, receiving hospice or palliative care, or resident in skilled nursing facilities.
* People who are pregnant or currently breastfeeding.
Inclusion Criteria:
Participants are eligible to be included in the study only if all of the following criteria apply:
* Male or female participants aged 18 to 75 years inclusive, at the time of signing the informed consent
* Participants who have had clinical evidence of active UC for ≥3 months before screening and confirmed by endoscopy during the screening period
* Must have active moderate-to-severe UC at screening as defined by a modified Mayo Score (mMS) of 5 to 9 (without the Physician Global Assessment (PGA), with a minimum Rectal Bleeding (RB) subscore ≥1, a minimum Stool Frequency (SF) subscore ≥1, mMES ≥2 confirmed by central reader, a minimum sum of all subscores of 5, and a minimum disease extent of 15 cm from the anal verge
* Must have received prior treatment for UC (either "a" or "b" below or combination of both):
1. History of inadequate response to, loss of response to or intolerance to standard treatment with any of the following compounds: amino-salicylates, corticosteroids, methotrexate, azathioprine, or 6-mercaptopurine, or history of corticosteroid dependence (defined as an inability to successfully taper corticosteroids without recurrence of UC) AND history of no prior exposure to Advanced Therapies (ATs), such as a biologic agent used to treat UC or advanced small molecules used to treat UC
2. History of inadequate response to, loss of response to or intolerance to treatment with ≥1 approved AT such as a biologic agent used to treat UC or advanced small molecules used to treat UC
* Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
Exclusion Criteria:
* Participants are excluded from the study if any of the following criteria apply:
* Participants with active Crohn's Disease (CD), indeterminate colitis or microscopic colitis
* Participants with fecal sample positive for culture/ova for aerobic pathogens or positive for Clostridium difficile B toxin in stools
* Participant with ostomy or ileoanal pouch, prior colectomy or anticipated colectomy during their participation in the study
* Participants with the following ongoing known complications of UC: fulminant disease, toxic megacolon or colonic dysplasia except for adenoma
* Participants with intestinal failure or short bowel syndrome requiring Total Parenteral Nutrition
* History of recurrent or recent serious infection within 4 weeks of screening, or infection(s) requiring hospitalization or treatment with IV anti-infectives within 30 days prior to baseline, or infections(s) requiring oral anti-infectives within 14 days prior to baseline, except as required as part of an anti-Tuberculosis (TB) regimen
* Known history of or suspected significant current immunosuppression.
* History or solid organ transplant or splenectomy
* History of moderate to severe congestive heart failure (New York Health Association Class III or IV), or recent cerebrovascular accident.
* History of demyelinating disease (including myelitis) or neurologic symptoms suggestive of demyelinating disease
* Participants with a history of malignancy or lymphoproliferative disease other than adequately treated localized carcinoma in situ of the cervix or nonmetastatic squamous cell carcinoma, or nonmetastatic basal cell carcinoma of the skin
* Participants with a diagnosis of inflammatory conditions other than UC (including but not limited to systemic lupus erythematosus, systemic sclerosis, myositis, rheumatoid arthritis, primary biliary cirrhosis, multiple sclerosis, Behcet's disease, sarcoidosis, etc.)
* History of Human Immunodeficiency Virus (HIV) infection or positive HIV serology at Screening
* History of Interstitial Lung Disease
* Participants with any of the following results at Screening:
* Positive (or indeterminate) Hepatitis B surface antigen (HBs Ag) or,
* Positive total Hepatitis B core antibody (anti-HBc) confirmed by positive Hepatitis B Virus (HBV) Deoxyribonucleic acid (DNA) or,
* Positive Hepatitis C Virus (HCV) antibody
* Screening laboratory and other analyses showing abnormal results
* History of any other condition which, in the opinion of the Investigator, would put the participant at risk by participation in the protocol
The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
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Inclusion Criteria:
Participants are eligible to be included in the study only if all of the following criteria apply:
* Male or female participants aged 18 to 75 years inclusive, at the time of signing the informed consent
* Participants who have had clinical evidence of active UC for ≥3 months before screening and confirmed by endoscopy during the screening period
* Must have active moderate-to-severe UC at screening as defined by a modified Mayo Score (mMS) of 5 to 9 (without the Physician Global Assessment (PGA), with a minimum Rectal Bleeding (RB) subscore ≥1, a minimum Stool Frequency (SF) subscore ≥1, mMES ≥2 confirmed by central reader and a minimum disease extent of 15 cm from the anal verge
* Must have received prior treatment for UC (either "a" or "b" below or combination of both):
1. History of inadequate response to, loss of response to or intolerance to standard treatment with any of the following compounds: amino-salicylates, corticosteroids, methotrexate, azathioprine, or 6-mercaptopurine, or history of corticosteroid dependence (defined as an inability to successfully taper corticosteroids without recurrence of UC) AND history of no prior exposure to approved Advanced Therapies (ATs), such as a biologic agent used to treat UC or advanced small molecules used to treat UC
2. History of inadequate response to, loss of response to or intolerance to treatment with ≥1 approved AT such as a biologic agent used to treat UC or advanced small molecules used to treat UC
* Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
Exclusion Criteria:
* Participants are excluded from the study if any of the following criteria apply:
* Participants with active Crohn's Disease (CD), indeterminate colitis or microscopic colitis
* Participants with fecal sample positive for culture/ova for aerobic pathogens or positive for Clostridium difficile B toxin in stools
* Participant with ostomy or ileoanal pouch, prior colectomy or anticipated colectomy during their participation in the study
* Participants with the following ongoing known complications of UC: fulminant disease, toxic megacolon or colonic dysplasia except for adenoma
* Participants with intestinal failure or short bowel syndrome requiring Total Parenteral Nutrition
* History of recurrent or recent serious infection within 4 weeks of screening, or infection(s) requiring hospitalization or treatment with IV anti-infectives within 30 days prior to baseline, or infections(s) requiring oral anti-infectives within 14 days prior to baseline, except as required as part of an anti-Tuberculosis (TB) regimen
* Known history of or suspected significant current immunosuppression.
* History or solid organ transplant or splenectomy
* History of moderate to severe congestive heart failure (New York Health Association Class III or IV), or recent cerebrovascular accident.
* History of demyelinating disease (including myelitis), family history of demyelinating disease, or neurologic symptoms suggestive of demyelinating disease
* Participants with a history of malignancy or lymphoproliferative disease other than adequately treated localized carcinoma in situ of the cervix or nonmetastatic squamous cell carcinoma, or nonmetastatic basal cell carcinoma of the skin
* Participants with a diagnosis of inflammatory conditions other than UC (including but not limited to systemic lupus erythematosus, systemic sclerosis, myositis, rheumatoid arthritis, primary biliary cirrhosis, multiple sclerosis, Behcet's disease, sarcoidosis, etc.)
* History of Human Immunodeficiency Virus (HIV) infection or positive HIV serology at Screening
* History of Interstitial Lung Disease
* Participants with any of the following results at Screening:
* Positive Hepatitis B surface antigen (HBs Ag) or,
* Positive total Hepatitis B core antibody (anti-HBcAB)
* Positive Hepatitis C Virus (HCV) antibody confirmed by positive HCV Ribonucleic Acid (RNA) (participants with HCV antibody (HCVAb) and negative HCV RNA may be included).
* Screening laboratory and other analyses showing abnormal results
* History of any other condition which, in the opinion of the Investigator, would put the participant at risk by participation in the protocol
The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Inclusion Criteria:
* 18 years of age or older at the time of enrollment.
* Has previously been diagnosed with moderate to severe cGvHD OR mild cGvHD with high-risk features (defined as platelet counts \< 100 x 109/L at screening).
* Capable of providing informed consent.
* Meets the criteria of steroid-refractory cGvHD after first line therapy at the time of enrollment, as follows:
* Lack of response or disease progression after prednisone ≥1 mg/kg/day for ≥1 week OR
* Disease persistence without improvement with prednisone \>0.5 mg/kg/day or 1 mg/kg/every other day for ≥4 weeks OR
* Increase in prednisone dose to \>0.25 mg/kg/day after 2 unsuccessful attempts to taper the dose.
* Taking a steroid dose at the time of enrollment that is \<0.5mg/kg/day of prednisone or equivalent.
* Absolute neutrophil count ≥ 1.5 × 109/L within 2 weeks (14 days) of enrollment.
* Platelet count ≥ 50 × 109/L within 2 weeks of enrollment.
* ALT and AST ≤ 5 × ULN (\<7.5 x ULN if due to liver GvHD) within 2 weeks of enrollment.
* Total bilirubin ≤ 1.5 × ULN within 2 weeks of enrollment.
* Glomerular filtration rate (GFR) ≥ 30 mL/min/1.73 m2 using the MDRD-4 variable formula within 2 weeks of enrollment.
* Female patients of childbearing potential will use 2 reliable methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study from the time of study enrollment until 3 months following the discontinuation of all study treatment and agree not to donate or cryopreserve eggs (ova, oocytes) for the purpose of reproduction during this period. Patients of childbearing potential are those who have not been surgically sterilized (i.e. have a documented hysterectomy, or documented bilateral salpingectomy, or documented bilateral oophorectomy) or have not been free from menses for \> 2 years. For individuals with permanent infertility due to an alternate medical cause other than the above (e.g. Mullerian agenesis, androgen insensitivity, gonadal dysgenesis) investigator discretion should be applied to determining study entry eligibility. Male patients will use an adequate method of contraception for the course of the study from the time of enrollment to 3 months after discontinuation of all study treatment. These participants must refrain from donating or cryopreserving sperm, be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent or must agree to use contraception (a male condom and an additional highly effective contraceptive method as described in section 4.2.3) when having sexual intercourse with a woman of childbearing potential who is not currently pregnant.
* Patients showing overlap syndrome with components of aGvHD at the time of enrollment are eligible to participate unless the acute component of their overlap syndrome is Grade 3 or 4.
* Must be able and willing to comply with study procedures.
Exclusion Criteria:
* Have never been treated with systemic steroids as first line therapy for cGvHD.
* Receiving \>0.5 mg/kg/day of prednisone or equivalent corticosteroids at the time of enrollment.
* Has had prior treatment with a JAK inhibitor or ROCK2 inhibitor within 8 weeks of enrollment. Participants who received a JAK inhibitor for aGvHD are eligible only if they achieved CR or PR prior to screening.
* Active uncontrolled bacterial, fungal, parasitic, or viral infection. Infections are considered controlled if appropriate therapy has been initiated and, at the time of screening, no signs of infection are present.
* Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection that requires treatment, or is at risk for HBV reactivation (i.e., positive HBsAg) within 4 weeks of enrollment. Participants with negative HBsAg and positive total HBc antibody may be included if HBV DNA is undetectable at the time of screening. Participants who are positive for HCV antibody are eligible only if PCR is negative for HCV RNA. Participants whose immune status is unknown or uncertain must have results confirming immune status before enrollment. Prior serology results within 2 years are acceptable for determining eligibility.
* Known active infection or history of human immunodeficiency virus (HIV).
* Evidence of relapsed primary hematologic disease, or receipt of treatment for relapse after the allo-HCT was performed. Patients treated with Donor Lymphocyte Infusion (DLI) who have developed GvHD will not be excluded if the primary hematological disease has resolved.
* Maintenance therapy for the primary hematologic disease started within 4 weeks before initiation of study treatment (Cycle 1 Day 1) or plans to start maintenance therapy after Day 1.
* Participants on mechanical ventilation,requiring oxygen support or with a FEV1 \< 30%.
* History or current diagnosis of cardiac disease indicating significant risk of safety for participation in the study, such as uncontrolled or significant cardiac disease, including any of the following:
1. Recent myocardial infarction (within 6 months of enrollment)
2. New York Heart Association Class III or IV congestive heart failure
3. Unstable angina (within 6 months of enrollment)
4. Clinically significant (symptomatic) cardiac arrhythmias (e.g. sustained ventricular tachycardia, and clinically significant second or third degree AV block without a pacemaker).
* Uncontrolled hypertension, defined as blood pressure that remains above 130/80 mmHg in spite of concurrent use of three antihypertensive agents of different classes.
* Patients with known active CNS disease (malignant involvement of CNS).
* Patients with active acute GvHD grade III-IV.
* History or other evidence of severe illness or any other conditions that would make the patient, in the opinion of the treating Investigator, unsuitable for the study (such as malabsorption syndromes, poorly controlled psychiatric disease or coronary artery disease).
* Known hypersensitivity to belumosudil, ruxolitinib or any of their excipients
* Patients unable to swallow oral medications
* Female participants who are pregnant or breastfeeding
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Inclusion Criteria:
1. 18 years of age or older at the time of enrollment.
2. Has previously been diagnosed with moderate to severe cGvHD OR mild cGvHD with high-risk features (defined as platelet counts \< 100 x 109/L at screening).
3. Capable of providing informed consent.
4. Meets the criteria of steroid-refractory cGvHD after first line corticosteroids therapy at the time of enrollment, as follows:
* Lack of response or disease progression after prednisone ≥1 mg/kg/day for ≥1 week OR
* Disease persistence without improvement with prednisone \>0.5 mg/kg/day or 1 mg/kg/every other day for ≥4 weeks OR
* Increase in prednisone dose to \>0.25 mg/kg/day after 2 unsuccessful attempts to taper the dose.
5. Taking a steroid dose at the time of enrollment that is \<0.5mg/kg/day of prednisone or equivalent.
6. Absolute neutrophil count ≥ 1.5 × 109/L within 2 weeks (14 days) of enrollment.
7. Platelet count ≥ 50 × 109/L within 2 weeks of enrollment.
8. ALT and AST ≤ 5 × ULN (\<7.5 x ULN if due to liver GvHD) within 2 weeks of enrollment.
9. Total bilirubin ≤ 1.5 × ULN within 2 weeks of enrollment.
10. Glomerular filtration rate (GFR) ≥ 30 mL/min/1.73 m2 using the MDRD-4 variable formula within 2 weeks of enrollment.
11. Female patients of childbearing potential will use 2 reliable methods of birth control (refer to Section 9.3) or be surgically sterile, or abstain from heterosexual activity for the course of the study from the time of study enrollment until 3 months following the discontinuation of all study treatment and agree not to donate or cryopreserve eggs (ova, oocytes) for the purpose of reproduction during this period. Patients of childbearing potential are those who have not been surgically sterilized (i.e. have a documented hysterectomy, or documented bilateral salpingectomy, or documented bilateral oophorectomy) or have not been free from menses for \> 2 years. For individuals with permanent infertility due to an alternate medical cause other than the above (e.g. Mullerian agenesis, androgen insensitivity, gonadal dysgenesis) investigator discretion should be applied to determining study entry eligibility.
Male patients will use an adequate method of contraception for the course of the study from the time of enrollment to 3 months after discontinuation of all study treatment. These participants must refrain from donating or cryopreserving sperm, be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent or must agree to use contraception (a male condom and an additional highly effective contraceptive method as described in Section 9.3) when having sexual intercourse with a woman of childbearing potential who is not currently pregnant.
12. Patients showing overlap syndrome with components of acute GvHD (aGvHD) at the time of enrollment are eligible to participate unless the acute component of their overlap syndrome is Grade 3 or 4.
13. Must be able and willing to comply with study procedures.
Exclusion Criteria:
1. Receiving ruxolitinib for active steroid refractory acute GvHD at the time of enrollment. Participants with a prior history of aGvHD are eligible only if the aGvHD has achieved CR or PR prior to screening and the participants subsequently developed steroid refractory cGvHD.
2. Have never been treated with systemic steroids as therapy for cGvHD.
3. Receiving \>0.5 mg/kg/day of prednisone or equivalent corticosteroids at the time of enrollment.
4. Ongoing use of any of the following pharmaceutical agents, which cannot be discontinued prior to belumosudil treatment (PRN/as-needed use is permissible if it can be fully discontinued at least 7 days prior to enrollment and is not expected to resume during the study):
* Strong CYP3A inducers
* UGT1A1 substrates (e.g., raltegravir)
* P-gp substrates (e.g., dabigatran)
* OATP1B1/OATP1B3/BCRP substrates (e.g., rosuvastatin)
5. Has had prior treatment with a JAK inhibitor or ROCK2 inhibitor within 8 weeks of enrollment. Participants who received a JAK inhibitor for aGvHD are eligible only if they achieved CR or PR prior to screening.
6. Active uncontrolled bacterial, fungal, parasitic, or viral infection. Infections are considered controlled if appropriate therapy has been initiated and, at the time of screening, no signs of infection are present.
7. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection that requires treatment, or is at risk for HBV reactivation (i.e., positive HBsAg) within 4 weeks of enrollment. Participants with negative HBsAg and positive total HBc antibody may be included if HBV DNA is undetectable at the time of screening. Participants who are positive for HCV antibody are eligible only if PCR is negative for HCV RNA. Participants whose immune status is unknown or uncertain must have results confirming immune status before enrollment.
8. Known active infection or history of human immunodeficiency virus (HIV).
9. Evidence of relapsed primary hematologic disease, or receipt of treatment for relapse after the allo-HCT was performed. Patients treated with Donor Lymphocyte Infusion (DLI) who have developed GvHD will not be excluded if the primary hematological disease has resolved.
10. Maintenance therapy for the primary hematologic disease started within 4 weeks before initiation of study treatment (Cycle 1 Day 1) or plans to start maintenance therapy after Day 1.
11. Participants on mechanical ventilation, requiring oxygen support or with a FEV1 \< 30%.
12. History or current diagnosis of cardiac disease indicating significant risk of safety for participation in the study, such as uncontrolled or significant cardiac disease, including any of the following:
1. Recent myocardial infarction (within 6 months of enrollment)
2. New York Heart Association Class III or IV congestive heart failure
3. Unstable angina (within 6 months of enrollment)
4. Clinically significant (symptomatic) cardiac arrhythmias (e.g. sustained ventricular tachycardia, and clinically significant second or third degree AV block without a pacemaker).
13. Uncontrolled hypertension, defined as blood pressure that remains above 130/80 mmHg in spite of concurrent use of at least three antihypertensive agents of different classes.
14. Patients with known active CNS disease (malignant involvement of CNS).
15. Patients with active acute GvHD grade III-IV.
16. History or other evidence of severe illness or any other conditions that would make the patient, in the opinion of the treating Investigator, unsuitable for the study (such as malabsorption syndromes, poorly controlled psychiatric disease or coronary artery disease).
17. Known hypersensitivity to belumosudil, ruxolitinib or any of their excipients
18. Patients unable to swallow oral medications
19. Female participants who are pregnant or breastfeeding
Inclusion Criteria:
* Aged 6 to 7 months on the day of inclusion
* Participants who are healthy as determined by medical evaluation including medical history, physical examination and judgment of the Investigator
Exclusion Criteria: Participants are excluded from the study if any of the following criteria apply:
* Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks) within the past 3 months
* History of meningococcal infection, confirmed either clinically, serologically, or microbiologically
* At high risk for meningococcal infection during the study (specifically but not limited to participants with persistent complement deficiency, with anatomic or functional asplenia, or participants traveling to countries with high endemic or epidemic disease)
* Personal history of Guillain-Barré syndrome
* Personal history of an Arthus-like reaction after vaccination with a tetanus toxoid-containing vaccine
* Known systemic hypersensitivity to any of the study intervention components, or history of a life-threatening reaction to the study intervention(s) used in the study or to a product containing any of the same substances
* Moderate or severe acute illness/infection (according to investigator judgment) or febrile illness (temperature ≥ 38.0°C \[≥ 100.4°F\]) on the day of study intervention administration. A prospective participant should not be included in the study until the condition has resolved or the febrile event has subsided
* Receipt of any vaccine (including COVID-19) and Meningococcal B vaccines) in the 4 weeks preceding the first and second study intervention administration or planned receipt of any vaccine (including COVID-19 and Meningococcal B vaccines) in the 4 weeks following any study intervention administration except for influenza vaccination, which may be received at least 2 weeks before or 2 weeks after the study interventions. This exception includes monovalent pandemic influenza vaccines and multivalent influenza vaccines.
* Previous vaccination against meningococcal A, C, W, or Y disease with either the trial vaccine or another vaccine (i.e., mono- or quadrivalent meningococcal conjugate vaccine) containing serogroups A, C, Y, or W.
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Inclusion Criteria:
* Aged 6 to 7 months on the day of inclusion
* Participants who were healthy as determined by medical evaluation including medical history, physical examination and judgment of the Investigator
Exclusion Criteria: Participants were excluded from the study if any of the following criteria apply:
* Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks) within the past 3 months
* History of meningococcal infection, confirmed either clinically, serologically, or microbiologically
* At high risk for meningococcal infection during the study (specifically but not limited to participants with persistent complement deficiency, with anatomic or functional asplenia, or participants traveling to countries with high endemic or epidemic disease)
* Personal history of Guillain-Barré syndrome
* Personal history of an Arthus-like reaction after vaccination with a tetanus toxoid-containing vaccine
* Known systemic hypersensitivity to any of the study intervention components, or history of a life-threatening reaction to the study intervention(s) used in the study or to a product containing any of the same substances
* Moderate or severe acute illness/infection (according to investigator judgment) or febrile illness (temperature ≥ 38.0°C \[≥ 100.4°F\]) on the day of study intervention administration. A prospective participant should not be included in the study until the condition has resolved or the febrile event has subsided
* Receipt of any vaccine (including COVID-19) and Meningococcal B vaccines) in the 4 weeks preceding the first and second study intervention administration or planned receipt of any vaccine (including COVID-19 and Meningococcal B vaccines) in the 4 weeks following any study intervention administration except for influenza vaccination, which may be received at least 2 weeks before or 2 weeks after the study interventions. This exception includes monovalent pandemic influenza vaccines and multivalent influenza vaccines.
* Previous vaccination against meningococcal A, C, W, or Y disease with either the trial vaccine or another vaccine (i.e., mono- or quadrivalent meningococcal conjugate vaccine) containing serogroups A, C, Y, or W.
Inclusion Criteria: Participant is diagnosed with moderate to severe hemophilia A (defined as less than or equal to (≤)5 percent (%) of endogenous FVIII clotting activity) at the time of consent/assent.
Participant is more than or equal to (≥)12 years old at the time of consent/assent.
Participant has existing synovial hypertrophy, defined as at least 1 eligible\* joint by the HEAD-US score (Synovitis score: 1 or 2) at the time of consent/assent.
Participant has at least 1 eligible\* joint without planned future major orthopedic procedures (example, arthroscopic synovectomy, radioisotopic or chemical synoviorthesis), or major orthopedic procedures in the past 3 months prior to the screening visit (Visit 1).
\*An eligible joint is a joint with existing synovial hypertrophy, as defined by a HEAD-US synovitis score of 1 or 2, considering hypertrophic synovium as an indication of the presence of synovitis Participant has received prophylactic treatment with hemophilia prophylaxis prescriptions in the last 12 months prior to the baseline visit (Visit 2).
Participant is capable of understanding the written Informed Consent Form (ICF)/assent form, provides a signed and witnessed written ICF/assent form, and agrees to comply with the protocol requirements.
If male, no contraceptive measures are required for this study.
If female, is not pregnant or breastfeeding, and one of the following conditions applies:
Is a women of nonchildbearing potential (WONCBP) Is a women of childbearing potential (WOCBP) and agrees to use a highly effective contraceptive method, with a failure rate of less than (\<)1 percent during the study treatment period (at least until the Week 52/ End of Treatment \[EoT\] visit).
A WOCBP must have a negative serum pregnancy test at the screening visit (Visit 1) Exclusion Criteria: Participants are excluded from the study if any of the following criteria apply:
Has other associated clotting disorders at the time of consent/assent. Is already under efanesoctocog alfa treatment. Has a current diagnosis of an factor VIII (FVIII) inhibitor, defined as inhibitor titer ≥0.60 BU/mL.
Has ITI within the last 2 years prior to the baseline visit (Visit 2). Has been enrolled in a concurrent clinical interventional study or exposed to other investigational drug(s) within 3 months prior to screening for this study.
Is currently in an institution because of regulatory or legal order (that is, is a prisoner or a patient who is legally institutionalized).
Is not suitable for participation, whatever the reason, as judged by the investigator, including medical or clinical conditions, or patients potentially at risk of noncompliance to study procedures.
Is an employee or family member of the investigator or site personnel. Is involved in a specific situation during study implementation or the course of the study that may raise ethics considerations.
Has hypersensitivity to efanesoctocog alfa or its components or any of its excipients that, in the opinion of the investigator, contraindicates participation in the study.
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Inclusion Criteria:
* Participant is diagnosed with moderate to severe hemophilia A (defined as less than or equal to (≤)5 percent (%) of endogenous FVIII clotting activity) at the time of consent/assent.
* Participant is more than or equal to (≥)12 years old at the time of consent/assent.
* Participant has existing synovial hypertrophy, defined as at least 1 eligible\* joint by the HEAD-US score (Synovitis score: 1 or 2) at the time of consent/assent.
* Participant has at least 1 eligible\* joint without planned future major orthopedic procedures (example, arthroscopic synovectomy, radioisotopic or chemical synoviorthesis), or major orthopedic procedures in the past 3 months prior to the screening visit (Visit 1).
\*An eligible joint is a joint with existing synovial hypertrophy, as defined by a HEAD-US synovitis score of 1 or 2, considering hypertrophic synovium as an indication of the presence of synovitis
* Participant has received prophylactic treatment with hemophilia prophylaxis prescriptions in the last 12 months prior to the baseline visit (Visit 2).
* Participant is capable of understanding the written Informed Consent Form (ICF)/assent form, provides a signed and witnessed written ICF/assent form, and agrees to comply with the protocol requirements.
* If male, no contraceptive measures are required for this study.
* If female, is not pregnant or breastfeeding, and one of the following conditions applies:
* Is a women of nonchildbearing potential (WONCBP)
* Is a WOCBP and agrees to use a highly effective contraceptive method, with a failure rate of less than (\<)1 percent during the study treatment period (at least until the Week 52/ End of Treatment \[EoT\] visit).
* A WOCBP must have a negative serum pregnancy test at the screening visit (Visit 1)
Exclusion Criteria:
* Participants are excluded from the study if any of the following criteria apply:
* Has other associated clotting disorders at the time of consent/assent.
* Is already under efanesoctocog alfa treatment.
* Has a current diagnosis of an factor VIII (FVIII) inhibitor, defined as inhibitor titer ≥0.60 BU/mL.
* Has ITI within the last 2 years prior to the baseline visit (Visit 2).
* Has been enrolled in a concurrent clinical interventional study or exposed to other investigational drug(s) within 3 months prior to screening for this study.
* Is currently in an institution because of regulatory or legal order (that is, is a prisoner or a patient who is legally institutionalized).
* Is not suitable for participation, whatever the reason, as judged by the investigator, including medical or clinical conditions, or patients potentially at risk of noncompliance to study procedures.
* Is an employee or family member of the investigator or site personnel.
* Is involved in a specific situation during study implementation or the course of the study that may raise ethics considerations.
* Has hypersensitivity to efanesoctocog alfa or its components or any of its excipients that, in the opinion of the investigator, contraindicates participation in the study.
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Inclusion Criteria:
* Diagnosis of Crohn's Disease (CD) for at least 3 months prior to screening
* Confirmed diagnosis of moderate-to-severe CD
* History of prior exposure to standard treatment (5-Amino Salicylates (5-ASAs), steroids, immunomodulators or antibiotics) or advanced therapies (ATs) (biologics or small molecules), but having inadequate response to, loss or response to or intolerance to at least one of these therapies
* On stable doses of standard treatments prior to screening (Oral 5-ASA compounds, Oral corticosteroids, Azathioprine (AZA), 6-Mercaptopurine (6-MP), or Methotrexate (MTX), or Antibiotics, etc.)
* Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
Exclusion Criteria:
* Participants with active Ulcerative Colitis (UC), indeterminate colitis, adenomatous colonic polyps not excised, colonic mucosal dysplasia (low- or high-grade dysplasia) or short bowel syndrome
* Participants with CD isolated to the stomach, duodenum, jejunum, or perianal region, without colonic or ileal involvement
* Participants with following ongoing known complications of CD:
* Any manifestation that might require bowel surgery while enrolled in the study
* Participant with ostomy or ileoanal pouch
* Participant diagnosed with conditions that could interfere with drug absorption including but not limited to short bowel syndrome
* Participant with surgical bowel resection within the past three months prior to screening, or a history of \>3 bowel resections
* History of any other condition which, in the opinion of the Investigator, would put the participant at risk by participation in the study
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
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Inclusion Criteria:
* Diagnosis of Crohn's Disease (CD) for at least 3 months prior to screening
* Confirmed diagnosis of moderate-to-severe CD
* History of prior exposure to standard treatment and having inadequate response to, loss of response to or intolerance to standard therapy with any of the following compounds: (5-Amino Salicylates (5-ASAs), 6-Mercaptopurine (6-MP), Azathioprine (AZA), Methotrexate (MTX), oral or corticosteroids or advanced therapies (ATs) (biologics or small molecules), but having inadequate response to, loss or response to or intolerance to at least one of these therapies
* On stable doses of standard treatments prior to screening (Oral 5-ASA compounds, Oral corticosteroids, AZA, 6-MP, or MTX, or Antibiotics, etc.)
* Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
Exclusion Criteria:
* Participants with active Ulcerative Colitis (UC), indeterminate colitis, adenomatous colonic polyps not excised, colonic mucosal dysplasia (low- or high-grade dysplasia) or short bowel syndrome
* Participants with CD isolated to the stomach, duodenum, jejunum, or perianal region, without colonic or ileal involvement
* Participants with following ongoing known complications of CD:
* Any manifestation that might require bowel surgery while enrolled in the study
* Participant with ostomy or ileoanal pouch
* Participant diagnosed with conditions that could interfere with drug absorption including but not limited to short bowel syndrome
* Participant with surgical bowel resection within the past three months prior to screening, or a history of \>3 bowel resections
* History of any other condition which, in the opinion of the Investigator, would put the participant at risk by participation in the study
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Inclusion Criteria:
\- Participants with CD123-expressing hematological neoplasm per the 5th edition of the WHO Classification of Hematolymphoid Tumors.
Substudy 01:
* Participants must be ≥18 years of age
* Confirmed diagnosis of Acute Myeloid Leukemia
* Ineligible for intensive chemotherapy. Ineligible for intensive chemotherapy is defined by the following criteria:
A) ≥ 75 years of age, OR
B) 18 to 74 years of age and meeting one or more of the following:
1. Eastern Cooperative Oncology Group (ECOG) performance status 2-3.
2. Cardiac history of congestive heart failure (CHF) requiring treatment or left ventricular ejection fraction (LVEF) ≤50% or symptomatic coronary heart disease confirmed by coronarography or cardiac imaging.
3. Diffusing capacity of the lungs for carbon monoxide (DLCO) ≤65% or forced expiratory volume (FEV1) ≤65%.
4. Creatinine clearance ≥30 to \<45 mL/min calculated by modification of diet in renal disease (MDRD) formula.
5. Moderate hepatic impairment with total bilirubin \>1.5 to ≤3.0x upper limit of normal (ULN).
* Subject with an Eastern Cooperative Oncology Group (ECOG) performance status as follows:
a) 0 to 2 for participants ≥75 years of age or b) 0 to 3 for participants 18 to 74 years of age.
* For participants ≥75 years of age, adequate renal function demonstrated by a creatinine clearance ≥30 mL/min, calculated by modification of diet in renal disease (MDRD)
* Subject with adequate liver function demonstrated by the following:
1. For participants 18 to 74 years of age, aspartate aminotransferase (AST) ≤3.0 × ULN, alanine aminotransferase (ALT) ≤3.0 × ULN and bilirubin ≤3.0 × ULN, unless considered due to leukemic organ involvement ˂5 × ULN.
2. For participants ≥75 years of age, aspartate aminotransferase (AST) ≤3.0 × ULN, alanine aminotransferase (ALT) ≤3.0 × ULN and bilirubin ≤1.5 × ULN, unless considered due to leukemic organ involvement ˂5 × ULN.
Exclusion Criteria:
* Any clinically significant, uncontrolled medical conditions (including any serious active systemic infection that is not controlled)
* Known second malignancy either progressing or requiring active treatment within the last 3 years prior to first IMP administration
* Known acquired immunodeficiency syndrome (AIDS-related illnesses) or HIV disease requiring antiretroviral treatment, or having active hepatitis B or C infection, or SARS-CoV-2 infection. With exception for:
1. HBV as determined by positive test for hepatitis B surface antigen (HBsAg) and/or HBV DNA. Participant who tests positive for anti-hepatitis B core (HBc) antigen IgG (with or without testing positive for anti-HBs), but tests negative for HBsAg and HBV DNA, is eligible.
2. A participant who tests positive for anti-HCV antibodies and has undetectable HCV RNA without receiving antiviral treatment for HCV is eligible.
* Active, known, or suspected clinically significant autoimmune disease that has required systemic treatment in the past 2 years prior to first IMP administration, except controlled by replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc)
* Predicted life expectancy ≤3 months.
* Medical conditions requiring treatment with medications with narrow therapeutic index that are substrates of CYP enzymes and that cannot be closely monitored to allow for dose adjustment.
* Ongoing adverse event of NCI CTCAE \[Version 5.0\] Grade 2 or greater severity cause by any prior anti-cancer therapy
Substudy 01:
* Patient with Acute Promyelocytic Leukemia (APL)
* Known active central nervous system involvement with AML at the time of enrollment as evidenced by cytology or pathology
* Cardiovascular disease of New York Heart Association (NYHA) Class ≥2.
* Malabsorption syndrome or other condition that precludes enteral route of administration
* A baseline QTc interval of (using the Fridericia correction calculation) \>470 msec.
* Subject has received treatment with at least one of the following:
1. A hypomethylating agent, venetoclax and/or chemo therapeutic agent for AML other than hydroxyurea used for disease control prior to the initiation of study therapy.
2. Experimental therapies for AML.
3. Concomitant medications of strong and moderate CYP3A inducers within 7 days prior to the initiation of study treatment.
The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
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Inclusion Criteria:
\- Participants with CD123-expressing hematological neoplasm per the 5th edition of the WHO Classification of Hematolymphoid Tumors.
Substudy 01:
* Participants must be ≥18 years of age
* Confirmed diagnosis of Acute Myeloid Leukemia
* Ineligible for intensive chemotherapy. Ineligible for intensive chemotherapy was defined by the following criteria:
A) ≥ 75 years of age, OR
B) 18 to 74 years of age and meeting one or more of the following:
1. Eastern Cooperative Oncology Group (ECOG) performance status 2-3.
2. Cardiac history of congestive heart failure (CHF) requiring treatment or left ventricular ejection fraction (LVEF) ≤50% or symptomatic coronary heart disease confirmed by coronarography or cardiac imaging.
3. Diffusing capacity of the lungs for carbon monoxide (DLCO) ≤65% or forced expiratory volume (FEV1) ≤65%.
4. Creatinine clearance ≥30 to \<45 mL/min calculated by modification of diet in renal disease (MDRD) formula.
5. Moderate hepatic impairment with total bilirubin \>1.5 to ≤3.0x upper limit of normal (ULN).
* Participant with an Eastern Cooperative Oncology Group (ECOG) performance status as follows:
a) 0 to 2 for participants ≥75 years of age or b) 0 to 3 for participants 18 to 74 years of age.
* For participants ≥75 years of age, adequate renal function demonstrated by a creatinine clearance ≥30 mL/min, calculated by modification of diet in renal disease (MDRD)
* Participant with adequate liver function demonstrated by the following:
1. For participants 18 to 74 years of age, aspartate aminotransferase (AST) ≤3.0 × ULN, alanine aminotransferase (ALT) ≤3.0 × ULN and bilirubin ≤3.0 × ULN, unless considered due to leukemic organ involvement ˂5 × ULN.
2. For participants ≥75 years of age, aspartate aminotransferase (AST) ≤3.0 × ULN, alanine aminotransferase (ALT) ≤3.0 × ULN and bilirubin ≤1.5 × ULN, unless considered due to leukemic organ involvement ˂5 × ULN.
Exclusion Criteria:
* Any clinically significant, uncontrolled medical conditions (including any serious active systemic infection that was not controlled)
* Known second malignancy either progressing or requiring active treatment within the last 3 years prior to first IMP administration
* Known acquired immunodeficiency syndrome (AIDS-related illnesses) or HIV disease requiring antiretroviral treatment, or having active hepatitis B or C infection, or SARS-CoV-2 infection. With exception for:
1. HBV as determined by positive test for hepatitis B surface antigen (HBsAg) and/or HBV DNA. Participant who tested positive for anti-hepatitis B core (HBc) antigen IgG (with or without testing positive for anti-HBs), but tested negative for HBsAg and HBV DNA, was eligible.
2. A participant who tested positive for anti-HCV antibodies and had undetectable HCV RNA without receiving antiviral treatment for HCV was eligible.
* Active, known, or suspected clinically significant autoimmune disease that had required systemic treatment in the past 2 years prior to first IMP administration, except controlled by replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc)
* Predicted life expectancy ≤3 months.
* Medical conditions requiring treatment with medications with narrow therapeutic index that were substrates of CYP enzymes and that could not be closely monitored to allow for dose adjustment.
* Ongoing adverse event of NCI CTCAE \[Version 5.0\] Grade 2 or greater severity cause by any prior anti-cancer therapy
Substudy 01:
* Patient with Acute Promyelocytic Leukemia (APL)
* Known active central nervous system involvement with AML at the time of enrollment as evidenced by cytology or pathology
* Cardiovascular disease of New York Heart Association (NYHA) Class ≥2.
* Malabsorption syndrome or other condition that precludes enteral route of administration
* A baseline QTc interval of (using the Fridericia correction calculation) \>470 msec.
* Participant had received treatment with at least one of the following:
1. A hypomethylating agent, venetoclax and/or chemo therapeutic agent for AML other than hydroxyurea used for disease control prior to the initiation of study therapy.
2. Experimental therapies for AML.
3. Concomitant medications of strong and moderate CYP3A inducers within 7 days prior to the initiation of study treatment.
The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
The study was terminated early due to low COVID-19 incidence and high population immunity, limiting meaningful vaccine efficacy assessment. The decision was made in consultation with FDA/CBER and was unrelated to safety concerns.
Inclusion Criteria:
For participation in SAD20411/MAD20412:
* Male and/or female participant, between 18 and 55 years of age, inclusive at the time of signing the ICF.
* Appearing healthy by a comprehensive clinical assessment (detailed medical history and complete physical examination).
For participation in MAD24339:
* Age ≥18 and ≤65 years of age at the time of signing informed consent.
* A diagnosis of HS made by a dermatologist at least 6 months prior to baseline visit.
* HS lesions present in at least 2 distinct anatomic areas (e. g., left and right axilla; or left axilla and left inguino-crural fold), one of which must be Hurley Stage II or Hurley Stage III.
* Total AN count of ≥4 at the baseline visit. - Draining tunnel count of ≤20 at the baseline visit.
Exclusion Criteria:
For participation in SAD20411/MAD20412:
\- Any history or presence of clinically relevant cardiovascular, pulmonary, gastrointestinal, dermatologic, hepatic, renal, metabolic, hematological, neurological, osteomuscular, articular, psychiatric, systemic, ocular, gynecologic (if female) or signs of acute illness. Active or chronic infection requiring systemic treatment within 4 weeks prior to baseline. Known history of immunosuppression or suspected current immunosuppression.
For participation in MAD24339:
* Any active skin disease or condition other than HS (including but not limited to inflammatory skin diseases and cutaneous infections) that may interfere with assessment of HS.
* Any active or chronic infection requiring systemic treatment (eg, antibiotics, antivirals, antifungals, antihelminthics) within 30 days prior to baseline.
* Use of prescription topical therapies for the treatment of HS within 14 days prior to the baseline visit. - Treatment with systemic antibiotics for HS within 14 days prior to the baseline visit. - Non-biologic systemic therapies with potential therapeutic impact on HS \<28 days or five half-lives prior to baseline visit.
* Any history of prior treatment with any systemic biologic with a potential therapeutic impact on HS.
The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
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Inclusion Criteria:
For participation in SAD20411/MAD20412:
* Male and/or female participant, between 18 and 55 years of age, inclusive at the time of signing the ICF.
* Appearing healthy by a comprehensive clinical assessment (detailed medical history and complete physical examination).
For participation in MAD24339:
* Age ≥18 and ≤65 years of age at the time of signing informed consent.
* A diagnosis of HS made by a dermatologist at least 6 months prior to baseline visit.
* HS lesions present in at least 2 distinct anatomic areas (e. g., left and right axilla; or left axilla and left inguino-crural fold), one of which must be Hurley Stage II or Hurley Stage III.
* Total AN count of ≥4 at the baseline visit. - Draining tunnel count of ≤20 at the baseline visit.
Exclusion Criteria:
For participation in SAD20411/MAD20412:
Any history or presence of clinically relevant cardiovascular, pulmonary, gastrointestinal, dermatologic, hepatic, renal, metabolic, hematological, neurological, osteomuscular, articular, psychiatric, systemic, ocular, gynecologic (if female) or signs of acute illness. Active or chronic infection requiring systemic treatment within 4 weeks prior to baseline. Known history of immunosuppression or suspected current immunosuppression.
For participation in MAD24339:
* Any active skin disease or condition other than HS (including but not limited to inflammatory skin diseases and cutaneous infections) that may interfere with assessment of HS.
* Any active or chronic infection requiring systemic treatment (eg, antibiotics, antivirals, antifungals, antihelminthics) within 30 days prior to baseline.
* Use of prescription topical therapies for the treatment of HS within 14 days prior to the baseline visit.
* Treatment with systemic antibiotics for HS within 14 days prior to the baseline visit.
* Non-biologic systemic therapies with potential therapeutic impact on HS \<28 days or five half-lives prior to baseline visit.
* Any history of prior treatment with any systemic biologic with a potential therapeutic impact on HS.
The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Inclusion Criteria:
* Aged 18 to 29 years on the day of inclusion
* New sex partner within the past 6 months, or more than one current sex partner, or partner with known previous or coexisting sexually transmitted infection (STI), or inconsistent condom use
* A female participant is eligible to participate if she is not pregnant or breastfeeding and one of the following conditions applies:
* Is of non-childbearing potential. To be considered of non-childbearing potential, a female must be surgically sterile.
OR
• Is of childbearing potential and agrees to use an effective contraceptive method from at least 4 weeks prior to study intervention administration until at least 4 weeks after the last study intervention administration.
* A female participant of childbearing potential must have a negative highly sensitive pregnancy test (urine or serum as required by local regulation) at the screening visit and before each subsequent study intervention administration
Exclusion Criteria:
* Any screening laboratory parameter with laboratory abnormalities as per local reference range and that are greater than Grade 2 or deemed clinically significant in the opinion of the Investigator
* Participants who are Chlamydia trachomatis (CT) and/or Neisseria gonorrhea (NG) NAAT positive at screening visit
* Self-reported or documented seropositivity for HIV antigen and/or antibodies (Abs), hepatitis B virus surface antigen (HBsAg), hepatitis B core antibodies (HBcAbs), or hepatitis C virus (HCV) Abs infection at screening visit
* Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months)
* Known systemic hypersensitivity to any of the study intervention components, or history of a life-threatening reaction to the study intervention(s) used in the study or to a product containing any of the same substances
* Previous history of myocarditis, pericarditis, and/or myopericarditis
* Known history of previous history of Guillain-Barre syndrome and other immune mediated demyelinating conditions that include but are not limited to Multiple Sclerosis (MS), Neuromyelitis Optica (NMO), acute disseminated encephalomyelitis (ADEM), Transverse myelitis
* Screening electrocardiogram (ECG) value that is consistent with possible myocarditis, pericarditis, and/or myopericarditis or screening ECG that demonstrates clinically relevant abnormalities, per investigator, that may affect participant safety or study results
* Self-reported thrombocytopenia, contraindicating intramuscular injection, based on investigator's judgment
* Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular injection, based on investigator's judgment
* Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with study conduct or completion
* Moderate or severe acute febrile illness (temperature ≥ 38.0°C \[≥ 100.4°F\]) on the day of study intervention administration. A prospective participant should not be included in the study until the condition has resolved or the febrile event has subsided
* Alcohol, prescription drug, or substance abuse that, in the opinion of the Investigator, might interfere with the study conduct or completion
* Receipt of any mRNA vaccine/product in the 2 months preceding study enrollment or planned receipt of any mRNA vaccine/product within the 2 months following any study intervention administration
* Receipt of any vaccine (other than the study vaccine) in the 4 weeks preceding any study intervention administration or planned receipt of any vaccine (other than the study vaccine) in the 4 weeks following any study intervention administration, except influenza which may be received at least 2 weeks before or 2 weeks after any study vaccination
* Receipt of immune globulins, blood, or blood-derived products in the past 3 months
Note: The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
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Inclusion Criteria:
* Aged 18 to 29 years (Chlamydia trachomatis seronegative) or 18 to 44 years (Chlamydia trachomatis seropositive) on the day of inclusion
* A female participant is eligible to participate if she is not pregnant or breastfeeding and one of the following conditions applies:
* Is of non-childbearing potential. To be considered of non-childbearing potential, a female must be surgically sterile.
OR
* Is of childbearing potential and agrees to use an effective contraceptive method from at least 4 weeks prior to study intervention administration until at least 4 weeks after the last study intervention administration.
* A female participant of childbearing potential must have a negative highly sensitive pregnancy test (urine or serum as required by local regulation) at the screening visit and before each subsequent study intervention administration.
Exclusion Criteria:
* Any screening laboratory parameter with laboratory abnormalities as per local reference range and that are greater than Grade 2 or deemed clinically significant in the opinion of the Investigator.
* Participants who are Chlamydia trachomatis (CT) and/or Neisseria gonorrhea (NG) NAAT positive at screening visit
* Self-reported or documented seropositivity for HIV antigen and/or antibodies (Abs), hepatitis B virus surface antigen (HBsAg), hepatitis B core antibodies (HBcAbs), or hepatitis C virus (HCV) Abs infection at screening visit.
* Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months).
* Known systemic hypersensitivity to any of the study intervention components, or history of a life-threatening reaction to the study intervention(s) used in the study or to a product containing any of the same substances.
* Previous history of myocarditis, pericarditis, and/or myopericarditis
* Known history of previous history of Guillain-Barre syndrome and other immune mediated demyelinating conditions that include but are not limited to Multiple Sclerosis (MS), Neuromyelitis Optica (NMO), acute disseminated encephalomyelitis (ADEM), Transverse myelitis.
* Screening electrocardiogram (ECG) value that is consistent with possible myocarditis, pericarditis, and/or myopericarditis or screening ECG that demonstrates clinically relevant abnormalities, per investigator, that may affect participant safety or study results.
* Self-reported thrombocytopenia, contraindicating intramuscular injection, based on investigator's judgment.
* Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular injection, based on investigator's judgment.
* Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with study conduct or completion.
* Moderate or severe acute febrile illness (temperature ≥ 38.0°C \[≥ 100.4°F\]) on the day of study intervention administration. A prospective participant should not be included in the study until the condition has resolved or the febrile event has subsided.
* Alcohol, prescription drug, or substance abuse that, in the opinion of the Investigator, might interfere with the study conduct or completion.
* Receipt of any mRNA vaccine/product in the 2 months preceding study enrollment or planned receipt of any mRNA vaccine/product within the 2 months following any study intervention administration.
* Receipt of any vaccine (other than the study vaccine) in the 4 weeks preceding any study intervention administration or planned receipt of any vaccine (other than the study vaccine) in the 4 weeks following any study intervention administration, except influenza which may be received at least 2 weeks before or 2 weeks after any study vaccination.
* Receipt of immune globulins, blood, or blood-derived products in the past 3 months.
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.