Clinical trial NCT06975722: A Study to Investigate the Efficacy and Safety of SAR442970 in Adult Participants With Ulcerative Colitis
Official title: A Phase 2b, Multi-national, Multi-center, Randomized, Double-blind, Placebo-controlled, Dose-ranging Study Followed by a Long-term Extension to Evaluate the Efficacy and Safety of SAR442970 in Adult Participants With Moderate to Severe Ulcerative Colitis
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Ulcerative Colitis
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2025-05-16
Enrollment: 99
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a phase 2b, randomized, double-blind, 3-arm study for the treatment of Ulcerative Colitis. The primary objective of this study is to assess the efficacy of different doses of SAR442970 compared with placebo in participants with moderate to severe Ulcerative Colitis. The total study duration is up to 169 weeks and the treatment duration is up to 158 weeks


Eligibility criteria: 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

NOTE - Additional criteria apply, please contact the investigator for more information

Primary outcomes:
measure: Proportion of participants who achieve clinical remission at the end of Week 16 by modified Mayo Score (mMS)
timeFrame: At Week 16
Secondary outcomes:
measure: Proportion of participants who achieve endoscopic improvement at Week 16
timeFrame: At Week 16
measure: Proportion of participants who achieve endoscopic improvement at Week 52
timeFrame: At Week 52
measure: Proportion of participants who achieve endoscopic response at Week 16
timeFrame: At Week 16
measure: Proportion of participants who achieve endoscopic response at Week 52
timeFrame: At Week 52
measure: Proportion of participants who achieve endoscopic remission at Week 16
timeFrame: At Week 16
measure: Proportion of participants who achieve endoscopic remission at Week 52
timeFrame: At Week 52
measure: Proportion of participants who achieve clinical remission by total Mayo Score (MS) at Week 16
timeFrame: At Week 16
measure: Proportion of participants who achieve clinical remission by total Mayo Score (MS) at Week 52
timeFrame: At Week 52
measure: Proportion of participants who achieve clinical response by total MS at Week 16
timeFrame: At Week 16
measure: Proportion of participants who achieve clinical response by total MS at Week 52
timeFrame: At Week 52
measure: Proportion of participants who achieve clinical response by mMS at Week 16
timeFrame: At Week 16
measure: Proportion of participants who achieve clinical response by mMS at Week 52
timeFrame: At Week 52
measure: Proportion of participants who achieve clinical remission by mMS at Week 52
timeFrame: At Week 52
measure: Change from baseline in PRO-2 (Patient Reported Outcome) total score (SF and RB)
timeFrame: From Baseline to Week 16 and up to End of Study (approximately 164 weeks)
measure: Change from baseline in mMS (SF, RB, and mMES)
timeFrame: From Baseline to Week 16 and up to End of Study (approximately 164 weeks)
measure: Change from baseline in Partial Mayo Score (PMS) (SF, RB, and Physician's Global Assessment [PGA])
timeFrame: From Baseline to Week 16 and up to End of Study (approximately 164 weeks)
measure: Proportion of participants who achieve histological improvement by Original Geboes Score (OGS) to assess inflammation in UC
timeFrame: At Week 16
measure: Proportion of participants who achieve histological remission by Robarts Histopathology Index (RHI)
timeFrame: At Week 16
measure: Proportion of participants who achieve histological remission by OGS to assess inflammation in UC
timeFrame: At Week 16
measure: Proportion of participants who achieve Histologic Endoscopic Mucosal Improvement (HEMI)
timeFrame: At Week 16
measure: Change from baseline in Inflammatory Bowel Disease Questionnaire (IBDQ)
timeFrame: From Baseline to Week 16
measure: Serum SAR442970 concentrations
timeFrame: Up to end of study (approximately 164 weeks)
measure: Incidence of Anti-drug Antibodies (ADAs)
timeFrame: Up to end of study (approximately 164 weeks)
measure: Number (percentage) of participants with any Treatment Emergent Adverse Events (TEAEs) during the Induction and Maintenance treatment periods
timeFrame: From start of induction period to Week 52
measure: Number (percentage) of participants with any TEAEs during the Long-term Extension (LTE) period
timeFrame: From Week 52 (start of LTE period) up to end of the study (approximately 164 weeks)
Other outcomes:
Locations:
Study officials:
References: