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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
260
Pharmaceutical form: Tablet Route of administration: Oral
Pharmaceutical form: Tablet Route of administration: Oral
GI Alliance - Arizona Digestive Health - Sun City- Site Number : 8400020
Sun City, Arizona, United States
Bristol Hospital- Site Number : 8400007
Bristol, Connecticut, United States
Novum Research- Site Number : 8400021
Clermont, Florida, United States
Homestead Associates in Research- Site Number : 8400012
Homestead, Florida, United States
Clinical Research of Osceola- Site Number : 8400013
Kissimmee, Florida, United States
Proportion of participants achieving endoscopic response
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.
Time frame: Week 12
Proportion of participants achieving clinical remission based on Crohn's Disease Activity Index (CDAI)
CDAI clinical remission is defined as CDAI score \<150. CDAI is a composite instrument that includes participant symptoms evaluated over 7 days (abdominal pain, stool frequency and general well-being), as well as presence of complications (arthritis/arthralgia, iritis/uveitis, erythema nodosum/pyoderma gangrenosum/aphthous stomatitis, anal fissure/fistula/abscess, other fistula, and fever), the use of antidiarrheal medicines, presence of an abdominal mass, hematocrit, and body weight. These items are scored individually, weighted, and do not contribute equally to the overall score. The CDAI is derived from summing up the weighted individual scores of eight items. CDAI approximately ranges from 0 to 600 with higher scores indicating more severe disease.
Time frame: Week 12
Proportion of participants achieving Patient-Reported Outcome (PRO-2) remission
PRO 2 remission is defined as the unweighted CDAI component of daily abdominal pain (AP) score ≤1, and the unweighted CDAI component of daily average stool frequency (SF) score ≤3 (ie, AP ≤1 and SF ≤3 and no worsening from baseline).
Time frame: Week 12
Proportion of participants achieving both clinical remission and endoscopic response
Clinical remission and endoscopic response based on CDAI \<150 and ≥50% reduction from baseline in centrally read Simple Endoscopic Score for Crohn's Disease (SES-CD)
Time frame: Week 12
Proportion of participants achieving endoscopic remission based on centrally read SES-CD
Endoscopic remission is defined as a centrally read SES-CD ≤4 points (SES-CD ≤2 points for isolated ileal disease) and a SES-CD decrease from baseline ≥2 points with no SES-CD sub score \>1 point
Time frame: From Baseline to Week 12
Proportion of participants achieving CDAI clinical response
CDAI clinical response is defined as a CDAI reduction from baseline ≥100 points.
Time frame: From Baseline to Week 12
Proportion of participants achieving Inflammatory Bowel Disease Questionnaire (IBDQ) remission
IBDQ remission is defined as IBDQ total score ≥170 points. The Inflammatory Bowel Disease Questionnaire (IBDQ) is used to assess health-related quality of life (HRQoL) in patients with inflammatory bowel disease. It consists of 32 questions evaluating bowel and systemic symptoms, as well as emotional and social functions. Each question is answered on a scale from 1 (worst) to 7 (best). The total score ranges from 32 to 224 with higher scores indicating better health-related quality of life.
Time frame: Week 12
Proportion of participants achieving IBDQ response
IBDQ response defined as an improvement of IBDQ scores by 27 points or more at Week 12 compared with baseline
Time frame: From baseline to Week 12
Change from baseline in the IBDQ scores
The total IBDQ score ranges from 32 to 224 which indicates better quality of life. A positive change from Baseline indicates improvement.
Time frame: From Baseline to week 12
Plasma pre-dose concentrations of SAR441566 at selected visits
Time frame: Up to week 52
Plasma post-dose concentrations of SAR441566 at selected visits
Time frame: Up to week 52
Number of participants experiencing any TEAEs
Any TEAEs, including any serious opportunistic infections, psoriasiform skin lesions or other immune mediated phenomena during double-blind (DB) induction and maintenance treatment period
Time frame: Up to week 52
Number of participants experiencing any TEAEs
Any TEAEs, including any serious opportunistic infections, psoriasiform skin lesions or other immune mediated phenomena during open-label treatment period
Time frame: From week 12 to week 52
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Wellness Clinical Research - Miami Lakes - 8181 Northwest 154th Street- Site Number : 8400010
Miami Lakes, Florida, United States
GCP Clinical Research- Site Number : 8400004
Tampa, Florida, United States
GI Alliance - Glenview- Site Number : 8400015
Glenview, Illinois, United States
Illinois Gastroenterology Group- Site Number : 8400011
Gurnee, Illinois, United States
University of Michigan Health System - Ann Arbor- Site Number : 8400017
Ann Arbor, Michigan, United States
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