Clinical trial NCT06867094: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Colitis Ulcerative
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2025-03-10
Enrollment: 204
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 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.

* 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.


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 combination of both):

  1. No prior exposure to Advanced Therapy (AT), but having inadequate response to, loss of response to or intolerance to standard treatment with any of the following compounds: 5-ASA, 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
  2. Inadequate response to, loss of response to or intolerance to treatment with ≥1 approved AT such as a biologic agent (such as TNF antagonists, anti-integrin other than natalizumab, anti-IL-12/23, anti-IL-23, or experimental biologic UC therapeutics), 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
* 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.

Primary outcomes:
measure: Proportion of participants achieving clinical remission at Week 12 by modified Mayo Score (mMS)
timeFrame: Week 12
Secondary outcomes:
measure: Proportion of participants achieving clinical response at Week 12 by modified Mayo Score (mMS)
timeFrame: Week 12
measure: Proportion of participants achieving clinical response at Week 12 by full Mayo score (MS)
timeFrame: Week 12
measure: Proportion of participants achieving clinical remission at Week 12 by full Mayo score (MS)
timeFrame: Week 12
measure: Proportion of participants achieving the combination of patient-reported outcome 2 (PRO2) remission and endoscopic remission at Week 12
timeFrame: Week 12
measure: Proportion of participants achieving endoscopic remission at Week 12
timeFrame: Week 12
measure: Change from baseline in PRO2 from randomization to Week 12
timeFrame: From Baseline to Week 12
measure: Proportion of participants achieving endoscopic response at Week 12
timeFrame: Week 12
measure: Proportion of participants achieving endoscopic improvement at Week 12
timeFrame: Week 12
measure: Proportion of participants achieving HEMI at Week 12
timeFrame: Week 12
measure: Plasma predose concentrations of SAR441566 at selected visits
timeFrame: Up to Week 52
measure: Plasma postdose concentrations of SAR441566 at selected visits
timeFrame: Up to Week 52
measure: Number of participants with any treatment-emergent adverse events (TEAEs) during induction and maintenance treatment period
timeFrame: Up to Week 52
measure: Number of participants with any reatment-emergent adverse events (TEAEs) during open-label treatment period
timeFrame: From Week 12 to Week 52
measure: Proportion achieving Inflammatory Bowel Disease Questionnaire (IBDQ) remission at Week 12
timeFrame: Week 12
measure: Proportion of participants achieving Inflammatory Bowel Disease Questionnaire (IBDQ) response at Week 12
timeFrame: Week 12
measure: Inflammatory Bowel Disease Questionnaire (IBDQ) response is defined as an increase from baseline in the total IBDQ score in the range of 16 to 32 points.
timeFrame: Week 12
Other outcomes:
Locations:
city: Bristol
country: United States
facility: Connecticut Clinical Research Institute- Site Number : 8400017
state: Connecticut
city: Miami Lakes
country: United States
facility: Wellness Clinical Research - Miami Lakes- Site Number : 8400002
state: Florida
city: Glenview
country: United States
facility: GI Alliance - Glenview- Site Number : 8400005
state: Illinois
city: Gurnee
country: United States
facility: Illinois Gastroenterology Group- Site Number : 8400004
state: Illinois
city: New York
country: United States
facility: A1 Clinical Network- Site Number : 8400011
state: New York
city: Uniontown
country: United States
facility: Frontier Clinical Research - Uniontown- Site Number : 8400006
state: Pennsylvania
city: Katy
country: United States
facility: Vitality Digestive Institute Clinical Research- Site Number : 8400007
state: Texas
city: Québec City
country: Canada
facility: Investigational Site Number : 1240001
Study officials:
References: