A Study to Investigate the Efficacy and Safety of SAR442970 in Adult Participants With Ulcerative Colitis

Phase 2RecruitingNCT06975722

Sanofi99 enrolled

Overview

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 168 weeks, with a treatment period of up to 158 weeks including an open-label (OL) long-term extension (LTE) period of up to 104 weeks for eligible participants.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Ulcerative Colitis

Interventions

SAR442970DRUG

Route of administration: Subcutaneous

PlaceboDRUG

Route of administration: Subcutaneous

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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.

Locations (67)

Outcomes

Primary Outcomes

Proportion of participants who achieve clinical remission at the end of Week 16 by modified Mayo Score (mMS)

Clinical remission is based on modified Mayo subscores. The mMS ranges from 0 to 9 with higher scores indicating greater disease severity.

Time frame: At Week 16

Secondary Outcomes

Proportion of participants who achieve endoscopic improvement at Week 16

Endoscopic improvement is defined as a modified Mayo Endoscopic Subscore (mMES) of 0 or 1 (where 1 does not include friability). The mMES ranges from 0 to 3 with higher scores indicating greater disease severity.

Time frame: At Week 16

Proportion of participants who achieve endoscopic improvement at Week 52

Endoscopic improvement is defined as an mMES of 0 or 1 (where 1 does not include friability). The mMES ranges from 0 to 3 with higher scores indicating greater disease severity.

Time frame: At Week 52

Proportion of participants who achieve endoscopic response at Week 16

Endoscopic response is defined as an mMES decrease of at least 1.

Time frame: At Week 16

Proportion of participants who achieve endoscopic response at Week 52

Endoscopic response is defined as an mMES decrease of at least 1.

Time frame: At Week 52

Proportion of participants who achieve endoscopic remission at Week 16

Endoscopic remission is defined as an mMES of 0.

Time frame: At Week 16

Proportion of participants who achieve endoscopic remission at Week 52

Central Contacts

Trial Transparency email recommended (Toll free for US & Canada)

CONTACT

800-633-1610 contact-us@sanofi.com

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Investigational Site Number: 8400009

Escondido, California, United States

RECRUITING

Investigational Site Number: 8400006

Lancaster, California, United States

RECRUITING

Investigational Site Number: 8400025

Thousand Oaks, California, United States

RECRUITING

Investigational Site Number: 8400024

Jacksonville, Florida, United States

RECRUITING

Investigational Site Number: 8400030

Kissimmee, Florida, United States

RECRUITING

Investigational Site Number: 8400003

Lighthouse PT, Florida, United States

RECRUITING

Investigational Site Number: 8400001

Miami, Florida, United States

RECRUITING

Investigational Site Number: 8400011

Miami, Florida, United States

RECRUITING

Investigational Site Number: 8400010

Palmetto Bay, Florida, United States

RECRUITING

Investigational Site Number: 8400019

Tampa, Florida, United States

RECRUITING

...and 57 more locations

Endoscopic remission is defined as an mMES of 0.

Time frame: At Week 52

Proportion of participants who achieve clinical remission by total Mayo Score (MS) at Week 16

Clinical remission is defined as total MS ≤2 with no subscore \>1. The total Mayo score (MS) is a composite index designed to measure ulcerative colitis (UC) disease activity and consists of 4 subscores: RB and SF, which are patient-reported subscores, Physician's global assessment (PGA), and endoscopic findings. Individual items are rated 0 to 3, giving the composite score a maximum of 12, with higher scores indicating greater disease severity.

Time frame: At Week 16

Proportion of participants who achieve clinical remission by total Mayo Score (MS) at Week 52

Clinical remission is defined as total MS ≤2 with no subscore \>1.

Time frame: At Week 52

Proportion of participants who achieve clinical response by total MS at Week 16

Clinical response by total MS is defined as a decrease from baseline in the total MS of ≥3 points and at least 30% reduction from baseline, and a decrease in the RB subscore of ≥1 or an absolute RB subscore of 0 or 1.

Time frame: At Week 16

Proportion of participants who achieve clinical response by total MS at Week 52

Time frame: At Week 52

Proportion of participants who achieve clinical response by mMS at Week 16

Clinical response by mMS is defined as a decrease from baseline in the mMS of ≥2 points and an improvement of ≥30% from baseline plus a decrease in RB subscore ≥1 or an absolute RB subscore ≤1.

Time frame: At Week 16

Proportion of participants who achieve clinical response by mMS at Week 52

Time frame: At Week 52

Proportion of participants who achieve clinical remission by mMS at Week 52

Clinical remission is defined as an mMS score of 0 to 2, including SF subscore of 0 or 1, RB subscore of 0, and mMES of 0 or 1 (score of 1 does not include friability).

Time frame: At Week 52

Change from baseline in PRO-2 (Patient Reported Outcome) total score (SF and RB)

PRO-2 (Patient Reported Outcome) score is defined as the sum of Mayo SF and RB subscores.

Time frame: From Baseline to Week 16 and up to End of Study (approximately 164 weeks)

Change from baseline in mMS (SF, RB, and mMES)

Each component of the mMS (SF, RB, and mMES) is scored from 0 to 3. The total mMS ranges from 0 to 9 with higher scores indicating greater disease severity.

Time frame: From Baseline to Week 16 and up to End of Study (approximately 164 weeks)

Change from baseline in Partial Mayo Score (PMS) (SF, RB, and Physician's Global Assessment [PGA])

The Partial Mayo Score (PMS) includes the SF, RB, and PGA components. It ranges from 0 to 9 with higher score indicating highest severity.

Time frame: From Baseline to Week 16 and up to End of Study (approximately 164 weeks)

Proportion of participants who achieve histological improvement by Original Geboes Score (OGS) to assess inflammation in UC

Histological improvement is defined as OGS ≤3.1. Original Geboes Score (OGS) is a 6-grade classification system that assesses inflammation severity. Each grade includes subgrades for more specific histological features. Assessment uses the worst area of the biopsy rather than the average. Higher grades indicate greater inflammatory activity in the colon.

Time frame: At Week 16

Proportion of participants who achieve histological remission by Robarts Histopathology Index (RHI)

Histological remission is defined as RHI ≤3. The Robarts Histopathology Index (RHI) assesses 4 characteristics of mucosal activity, inflammatory infiltrate, lamina propria neutrophils, neutrophils in epithelium, and erosion or ulceration, all of which are rated on a scale of 0 to 3. Each characteristic is weighted to produce a total score ranging from 0 (no disease activity) to 33 (most severe disease activity).

Time frame: At Week 16

Proportion of participants who achieve histological remission by OGS to assess inflammation in UC

Histological remission is defined as OGS \<2B.1.

Time frame: At Week 16

Proportion of participants who achieve Histologic Endoscopic Mucosal Improvement (HEMI)

HEMI is defined by achievement of modified Mayo endoscopic improvement (mMES of 0 or 1 where 1 does not include friability) and histologic improvement (OGS ≤3.1).

Time frame: At Week 16

Change from baseline in Inflammatory Bowel Disease Questionnaire (IBDQ)

This captures the patient's experience of inflammatory bowel disease (IBD) on 4 domains of functioning and well-being: bowel and systemic symptoms and emotional and social function. The Inflammatory Bowel Disease Questionnaire (IBDQ) is a 32-item instrument assessing health-related quality of life in IBD patients across four dimensions: bowel symptoms (10 items), systemic symptoms (5 items), emotional function (12 items), and social function (5 items). Each question evaluates experiences over the previous two weeks on a 7-point Likert scale from 1 (worst) to 7 (best). The total score ranges from 32 to 224, with higher scores indicating better quality of life. Both domain-specific and overall scores can be calculated.

Time frame: From Baseline to Week 16

Serum SAR442970 concentrations

Time frame: Up to end of study (approximately 164 weeks)

Incidence of Anti-drug Antibodies (ADAs)

Time frame: Up to end of study (approximately 164 weeks)

Number (percentage) of participants with any Treatment Emergent Adverse Events (TEAEs) during the Induction and Maintenance treatment periods

Time frame: From start of induction period to Week 52

Number (percentage) of participants with any TEAEs during the Long-term Extension (LTE) period

Time frame: From Week 52 (start of LTE period) up to end of the study (approximately 164 weeks)