A Phase 2, Multinational, Multicenter, Randomized, Doubleblind, Placebocontrolled, Dose-ranging Study to Evaluate the Efficacy and Safety of SAR441566 in Adults With Moderate to Severe Crohn's Disease.
Overview
- Phase
- Phase 2
- Intervention
- SAR441566
- Conditions
- Crohn's Disease
- Sponsor
- Sanofi
- Enrollment
- 260
- Locations
- 272
- Primary Endpoint
- Proportion of participants achieving endoscopic response
- Status
- Recruiting
- Last Updated
- 11 days ago
Overview
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 Crohn's Disease (CD). The primary objective of this study is to assess the efficacy of different doses of SAR441566 compared with placebo in participants with moderate to severe CD.
This study will have an anticipated duration of up to 59 weeks which will include a screening period of 4 weeks (+7 calendar days if needed), followed by the Main Study (MS) treatment period, lasting 52 weeks, and a 2-week follow-up period after end of treatment for participants not enrolling in the Long Term Safety (LTS) study. The MS period includes a Double-Blind (DB) treatment period with 12 weeks of induction followed by 40 weeks of maintenance.
Additionally, an Open Label (OL) period of up to 40 weeks will be offered to eligible participants. The combined duration of the DB maintenance and OL periods cannot exceed 40 weeks, depending on when participants switch.
Investigators
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 at the time of signing the ICF
- •Confirmed diagnosis of CD for at least 3 months prior to Baseline
- •Confirmed diagnosis of moderate to severe CD as assessed by:
- •Crohn's Disease Activity Index (CDAI) score and the Simple Endoscopic Score for Crohn's disease (SES-CD) on an endoscopy confirmed by a central reader
- •stool frequency (SF), abdominal pain (AP) score
- •History of prior exposure to standard treatment (5-ASA, steroids, immunomodulators or antibiotics) or advanced therapies (biologics or small molecules), but having inadequate response to, loss or response to or intolerance to at least one of these therapies
- •On stable doses of standard treatments prior to screening (oral 5-ASA compounds, oral corticosteroids, thiopurines (eg. AZA, 6-MP), or MTX)
- •Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Women participants should not be pregnant or breastfeeding.
Exclusion Criteria
- •Participants are excluded from the study if any of the following criteria apply:
- •Participants with active UC, indeterminate colitis or short bowel syndrome
- •Participants with CD isolated to the stomach, duodenum, jejunum, or peri anal region, without colonic or ileal involvement
- •Participants with following ongoing known complications of CD: fistula, abscess, symptomatic stricture/stenosis, fulminant colitis, toxic megacolon, recent bowel resection within 3 months of screening or history of \> 3 bowel resections
- •Participants with stool sample positive for infectious pathogens
- •Participants with active tuberculosis (TB) or a history of incompletely treated active or latent TB per local guidelines
- •Participants with Positive Hepatitis B surface antigen (HBsAg) or positive Hepatitis B core antibody (HBcAb); and/or positive Hepatitis C antibody (HCV) 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
Arms & Interventions
SAR441566 dose 1
Participants will receive SAR441566 dose 1.
Intervention: SAR441566
SAR441566 dose 2
Participants will receive SAR441566 dose 2.
Intervention: SAR441566
SAR441566 dose 3
Participants will receive SAR441566 dose 3.
Intervention: SAR441566
Placebo
Participants will receive SAR441566 matching placebo.
Intervention: SAR441566 matching Placebo
Outcomes
Primary Outcomes
Proportion of participants achieving endoscopic response
Time Frame: Week 12
Endoscopic response is defined as ≥50% reduction from baseline in centrally read Simple Endoscopic Score for Crohn's Disease (SES-CD). The SES-CD evaluates 4 endoscopic variables (ulcer size, ulcerated surface, affected surface, and narrowing, each on a scale from 0 (none) to 3 in 5 segments assessed during ileocolonoscopy (ileum, right colon, transverse colon, sigmoid and left colon, and rectum). The total score is the sum of the 4 endoscopic variable scores and ranges from 0 to 56, where higher scores indicate more severe disease.
Secondary Outcomes
- Proportion of participants achieving IBDQ response(From baseline to Week 12)
- Change from baseline in the IBDQ scores(From Baseline to week 12)
- Proportion of participants achieving CDAI clinical response(From Baseline to Week 12)
- Proportion of participants achieving Inflammatory Bowel Disease Questionnaire (IBDQ) remission(Week 12)
- Proportion of participants achieving clinical remission based on Crohn's Disease Activity Index (CDAI)(Week 12)
- Proportion of participants achieving Patient-Reported Outcome (PRO-2) remission(Week 12)
- Proportion of participants achieving both clinical remission and endoscopic response(Week 12)
- Proportion of participants achieving endoscopic remission based on centrally read SES-CD(From Baseline to Week 12)
- Proportion of participants achieving clinical remission based on Crohn's Disease Activity Index (CDAI)(Week 12)
- Proportion of participants achieving Patient-Reported Outcome (PRO-2) remission(Week 12)
- Proportion of participants achieving both clinical remission and endoscopic response(Week 12)
- Proportion of participants achieving endoscopic remission based on centrally read SES-CD(From Baseline to Week 12)
- Proportion of participants achieving CDAI clinical response(From Baseline to Week 12)
- Proportion of participants achieving Inflammatory Bowel Disease Questionnaire (IBDQ) remission(Week 12)
- Proportion of participants achieving IBDQ response(From baseline to Week 12)
- Change from baseline in the IBDQ scores(From Baseline to week 12)
- Plasma pre-dose concentrations of SAR441566 at selected visits(Up to week 52)
- Plasma post-dose concentrations of SAR441566 at selected visits(Up to week 52)
- Number of participants experiencing any TEAEs(From week 12 to week 52)
- Number of participants experiencing any TEAEs(Up to week 52)