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

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.

Interventions

• Drug SAR442970
  Route of administration: Subcutaneous
• Drug Placebo
  Route of administration: Subcutaneous

Primary outcome measures

• Proportion of participants who achieve clinical remission at the end of Week 16 by modified Mayo Score (mMS) [Time frame: At Week 16]

Secondary outcome measures (12)

• Proportion of participants who achieve endoscopic improvement at Week 16 [Time frame: At Week 16]
• Proportion of participants who achieve endoscopic improvement at Week 52 [Time frame: At Week 52]
• Proportion of participants who achieve endoscopic response at Week 16 [Time frame: At Week 16]
• Proportion of participants who achieve endoscopic response at Week 52 [Time frame: At Week 52]
• Proportion of participants who achieve endoscopic remission at Week 16 [Time frame: At Week 16]
• Proportion of participants who achieve endoscopic remission at Week 52 [Time frame: At Week 52]
• Proportion of participants who achieve clinical remission by total Mayo Score (MS) at Week 16 [Time frame: At Week 16]
• Proportion of participants who achieve clinical remission by total Mayo Score (MS) at Week 52 [Time frame: At Week 52]
• Proportion of participants who achieve clinical response by total MS at Week 16 [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 [Time frame: At Week 16]
• Proportion of participants who achieve clinical response by mMS at Week 52 [Time frame: At Week 52]

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):

• 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
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 21 centers

• Investigational Site Number: 8400009 — Escondido
• Investigational Site Number: 8400006 — Lancaster
• Investigational Site Number: 8400025 — Thousand Oaks
• Investigational Site Number: 8400024 — Jacksonville
• Investigational Site Number: 8400030 — Kissimmee
• Investigational Site Number: 8400003 — Lighthouse PT
• Investigational Site Number: 8400001 — Miami
• Investigational Site Number: 8400011 — Miami
• … and 13 more centers

Poland · 9 centers

• Investigational Site Number: 6160006 — Wroclaw
• Investigational Site Number: 6160002 — Bydgoszcz
• Investigational Site Number: 6160009 — Chojnice
• Investigational Site Number: 6160007 — Katowice
• Investigational Site Number: 6160005 — Sopot
• Investigational Site Number: 6160008 — Tychy
• Investigational Site Number: 6160004 — Warsaw
• Investigational Site Number: 6160003 — Warsaw
• … and 1 more center

China · 8 centers

• Investigational Site Number: 1560004 — Huizhou
• Investigational Site Number: 1560005 — Guangzhou
• Investigational Site Number: 1560002 — Nanjing
• Investigational Site Number: 1560008 — Suzhou
• Investigational Site Number: 1560003 — Wuxi
• Investigational Site Number: 1560009 — Shanghai
• Investigational Site Number: 1560001 — Hangzhou
• Investigational Site Number: 1560007 — Ningbo

France · 6 centers

• Investigational Site Number: 2500002 — Lille
• Investigative Site: 2500006 — Nice
• Investigational Site Number: 2500005 — Pierre-Bénite
• Investigational Site Number: 2500001 — Saint-Priest-en-Jarez
• Investigational Site Number: 2500003 — Toulouse
• Investigational Site Number: 2500004 — Vandœuvre-lès-Nancy

Japan · 6 centers

• Investigational Site Number: 3920002 — Kashiwa
• Investigational Site Number: 3920006 — Ōita
• Investigational Site Number: 3920005 — Hamamatsu
• Investigational Site Number: 3920003 — Hirosaki
• Investigational Site Number: 3920001 — Morioka
• Investigational Site Number: 3920004 — Nishinomiya

United Kingdom · 4 centers

• Investigational Site Number: 8260002 — Northwich
• Investigational Site Number: 8260003 — Bury
• Investigational Site Number: 8260001 — London
• Investigational Site Number: 8260004 — London

Germany · 3 centers

• Investigational Site Number: 2760001 — Minden
• Investigational Site Number: 2760005 — Kiel
• Investigational Site Number: 2760003 — Ulm

Hungary · 3 centers

• Investigational Site Number: 3480003 — Budapest
• Investigational Site Number: 3480002 — Budapest
• Investigational Site Number: 3480001 — Vác

Australia · 2 centers

• Investigational Site Number: 0360003 — Brisbane
• Investigational Site Number: 0360001 — Clayton

Czechia · 2 centers

• Investigational Site Number: 2030001 — Brno
• Investigational Site Number: 2030002 — Slaný

Spain · 2 centers

• Investigational Site Number: 7240001 — Las Palmas de Gran Canaria
• Investigational Site Number: 7240002 — Madrid

Moldova · 1 center

• Investigational Site Number: 4980001 — Chisinau

Identifiers

NCT: NCT06975722 · ACT18134 · 2024-515241-41-00 · U1111-1305-7281 · ACT18134

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗