A Study to Investigate Efficacy and Safety of SAR441566 in Patients With Ulcerative Colitis

Official title

A Phase 2, Multinational, Multicenter, Randomized, Double-blind, Placebo-controlled, Dose-ranging Study to Evaluate the Efficacy and Safety of SAR441566 in Adults With Moderate-to-severe Ulcerative Colitis

Overview

This is a Phase 2, multinational, multicenter, randomized, double-blind, placebo-controlled, dose ranging study to evaluate the efficacy and safety of SAR441566 in adults with moderate-to-severe UC. The primary objective of this study is to assess efficacy of different doses of SAR441566 on clinical remission in participants with moderate-to-severe ulcerative colitis. This study will include a screening period of up to 28 days (+ 7 calendar days if needed) followed by the main study treatment period of 52 weeks which will be comprised of a double blind (DB) treatment period with 12 weeks of induction period followed by a maintenance period of 40 weeks and 2-week follow-up after end of treatment. Additionally, an Open Label (OL) period of up to 40 weeks will be offered to eligible participants (for participants not enrolling in the LTS study). * The study duration will be up to 59 weeks. * The treatment duration will be up to 52 weeks in the DB arm and up to 40 weeks in the OL arm. * The number of visits will be 12 for the main study treatment period and 8 for the OL treatment period.

Interventions

• Drug SAR441566
  Pharmaceutical form: Tablet Route of administration: Oral
• Drug SAR441566 matching Placebo
  Pharmaceutical form: Tablet Route of administration: Oral

Primary outcome measures

• Proportion of participants achieving clinical remission at Week 12 by modified Mayo Score (mMS) [Time frame: Week 12]

Secondary outcome measures (12)

• Proportion of participants achieving clinical response at Week 12 by modified Mayo Score (mMS) [Time frame: Week 12]
• Proportion of participants achieving clinical response at Week 12 by full Mayo score (MS) [Time frame: Week 12]
• Proportion of participants achieving clinical remission at Week 12 by full Mayo score (MS) [Time frame: Week 12]
• Proportion of participants achieving the combination of patient-reported outcome 2 (PRO2) remission and endoscopic remission at Week 12 [Time frame: Week 12]
• Proportion of participants achieving endoscopic remission at Week 12 [Time frame: Week 12]
• Change from baseline in PRO2 from randomization to Week 12 [Time frame: From Baseline to Week 12]
• Proportion of participants achieving endoscopic response at Week 12 [Time frame: Week 12]
• Proportion of participants achieving endoscopic improvement at Week 12 [Time frame: Week 12]
• Proportion of participants achieving HEMI at Week 12 [Time frame: Week 12]
• Plasma predose concentrations of SAR441566 at selected visits [Time frame: Up to Week 52]
• Plasma postdose concentrations of SAR441566 at selected visits [Time frame: Up to Week 52]
• Number of participants with any treatment-emergent adverse events (TEAEs) during induction and maintenance treatment period [Time frame: Up to 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 clinical evidence of active UC for ≥3 months before screening and confirmed by endoscopy during the screening period
• 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, a mMES ≥2 confirmed by central reader, a minimum sum of all subscores of 5, and a disease extent >15 cm from the anal verge
• Must have received prior treatment for UC (either "a" or "b" below or a combination of both "a" and "b"):

• History of no prior exposure to approved Advanced Therapy (AT), but having inadequate response to, loss of response to or intolerance to standard treatment with any of the following : 5-ASA, thiopurines (eg.6-MP, AZA), MTX, oral or intravenous (IV) corticosteroids or history of corticosteroid dependence (defined an inability to successfully taper corticosteroids without recurrence of UC) OR
• History of inadequate response to, loss of response to or intolerance to treatment with ≥1 approved AT such as a biologic agent (eg. TNF antagonists, anti-integrin other than natalizumab, anti-IL-12/23, anti-IL-23, or a small molecule (such as a JAKi or S1PRm) for 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 CD, indeterminate colitis, ischemic colitis, microscopic colitis
• Participants with the following ongoing known complications of UC: fulminant colitis, toxic megacolon, or any other manifestation that might require bowel surgery while enrolled in the study
• Participant with prior colectomy, ostomy or ileoanal pouch, or anticipated colectomy during their participation in the study
• Participants with fecal sample positive for ova or parasites, bacterial pathogens, or positive for Clostridium difficile B toxin in stools
• Participants with active tuberculosis (TB) or a history of incompletely treated active TB or latent TB infection per local guidelines
• Participants with Positive Hepatitis B surface antigen (HBsAg), or hepatitis B core antibody (HBcAb) and/or hepatitis C virus antibody (HCVAb) at the screening visit
• Participants with any other active, chronic or recurrent infection, including recurrent or disseminated herpes zoster or disseminated herpes simplex
• Participants with a known history of human immunodeficiency virus (HIV) infection or positive HIV-1 or HIV-2 serology at screening
• Participants presenting with active malignancies, lymphoproliferative disease, or recurrence of either, within the 5 years before screening
• History of gastro-intestinal dysplasia other than completely removed low grade dysplasia OR presence of colonic mucosal dysplasia or adenomatous colonic polyps not removed during endoscopy by the time of the screening visit.
• If the participant has extensive colitis for ≥8 years or disease limited to left side of colon (ie, distal to splenic flexure) for >10 years, regardless of age, a colonoscopy within 1 year of the screening visit is required to survey for dysplasia. Participants with dysplasia or cancer identified on biopsies will be excluded.
• Female participants who is pregnant, breastfeeding, or is considering becoming pregnant during the study or within 3 months after the last dose of study drug
• Infection(s) requiring treatment with IV anti-infectives within 30 days prior to the screening visit or oral/intramuscular anti-infectives within 14 days prior to the screening visit
• Participants requiring or receiving any parental nutrition and/or exclusive enteral nutrition
• Participants who received cyclosporine, tacrolimus, mycophenolate mofetil, or thalidomide within 30 days prior to screening
• Participants who received fecal microbial transplantation within 30 days prior to screening
• Participants who have ever been exposed to natalizumab (Tysabri®) or oral carotegrast methyl (Carogra®)
• Participants who received IV corticosteroids within 14 days prior to screening or during screening period
• Screening laboratory and other analyses show abnormal results.

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 · 19 centers

• GI Alliance - Arizona Digestive Health - Sun City- Site Number : 8400003 — Sun City
• Bristol Hospital- Site Number : 8400017 — Bristol
• Novum Research- Site Number : 8400018 — Clermont
• Clinical Research of Osceola- Site Number : 8400012 — Kissimmee
• Wellness Clinical Research - Miami Lakes - 8181 Northwest 154th Street- Site Number : 8400 — Miami Lakes
• GCP Clinical Research- Site Number : 8400016 — Tampa
• GI Alliance - Glenview- Site Number : 8400005 — Glenview
• Illinois Gastroenterology Group- Site Number : 8400004 — Gurnee
• … and 11 more centers

Japan · 14 centers

Center list to be confirmed — check the primary protocol.

Italy · 10 centers

• Investigational Site Number : 3800006 — Genoa
• Investigational Site Number : 3800002 — Milan
• … and 8 more centers

China · 9 centers

• Investigational Site Number : 1560002 — Guangzhou
• Investigational Site Number : 1560001 — Hangzhou
• Investigational Site Number : 1560003 — Huizhou
• Investigational Site Number : 1560017 — Huizhou
• Investigational Site Number : 1560004 — Jiazhuang
• Investigational Site Number : 1560014 — Linhai
• Investigational Site Number : 1560008 — Luoyang
• Investigational Site Number : 1560005 — Shanghai
• … and 1 more center

India · 8 centers

• Investigational Site Number : 3560005 — Hyderabad
• Investigational Site Number : 3560003 — Jaipur
• Investigational Site Number : 3560009 — Jaipur
• Investigational Site Number : 3560002 — Kolkata
• Investigational Site Number : 3560004 — Ludhiana
• Investigational Site Number : 3560007 — Secunderabad
• Investigational Site Number : 3560001 — Surat
• Investigational Site Number : 3560010 — Visakhapatnam

Germany · 7 centers

• Investigational Site Number : 2760005 — Berlin
• Investigational Site Number : 2760008 — Berlin
• Investigational Site Number : 2760010 — Duisburg
• Investigational Site Number : 2760009 — Frankfurt
• Investigational Site Number : 2760003 — Hanover
• Investigational Site Number : 2760011 — Tübingen
• Investigational Site Number : 2760006 — Ulm

Argentina · 5 centers

• Investigational Site Number : 0320004 — San Miguel de Tucumán
• Investigational Site Number : 0320003 — Buenos Aires
• Investigational Site Number : 0320002 — Buenos Aires
• Investigational Site Number : 0320001 — Buenos Aires
• Investigational Site Number : 0320005 — Buenos Aires

Poland · 5 centers

Center list to be confirmed — check the primary protocol.

South Africa · 5 centers

Center list to be confirmed — check the primary protocol.

Austria · 3 centers

• Investigational Site Number : 0400003 — Graz
• Investigational Site Number : 0400002 — Salzburg
• Investigational Site Number : 0400001 — Vienna

Bulgaria · 3 centers

• Investigational Site Number : 1000001 — Burgas
• Investigational Site Number : 1000003 — Rousse
• Investigational Site Number : 1000002 — Sofia

Canada · 3 centers

• Investigational Site Number : 1240004 — Kentville
• Investigational Site Number : 1240005 — Richmond Hill
• Investigational Site Number : 1240001 — Québec

Chile · 3 centers

• Investigational Site Number : 1520002 — Santiago
• Investigational Site Number : 1520003 — Santiago
• Investigational Site Number : 1520001 — Santiago

France · 3 centers

• Investigational Site Number : 2500003 — Nice
• Investigational Site Number : 2500001 — Toulouse
• Investigational Site Number : 2500002 — Vandœuvre-lès-Nancy

Georgia · 3 centers

• Investigational Site Number : 2680002 — Tbilisi
• Investigational Site Number : 2680003 — Tbilisi
• Investigational Site Number : 2680001 — Tbilisi

Greece · 3 centers

• Investigational Site Number : 3000001 — Athens
• Investigational Site Number : 3000003 — Athens
• Investigational Site Number : 3000002 — Heraklion

Turkey (Türkiye) · 3 centers

Center list to be confirmed — check the primary protocol.

Australia · 2 centers

• Investigational Site Number : 0360003 — Kurralta Park
• Investigational Site Number : 0360005 — Richmond

Belgium · 2 centers

• Investigational Site Number : 0560002 — Ghent
• Investigational Site Number : 0560001 — Leuven

Brazil · 2 centers

• Hospital de Clinicas de Porto Alegre- Site Number : 0760002 — Porto Alegre
• Hospital Ernesto Dornelles- Site Number : 0760003 — Porto Alegre

Czechia · 2 centers

• Investigational Site Number : 2030001 — Olomouc
• Investigational Site Number : 2030002 — Ostrava

Hungary · 1 center

• Investigational Site Number : 3480001 — Budapest

Identifiers

NCT: NCT06867094 · DRI17822 · U1111-1308-9729 · 2025-520705-12

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗