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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
204
Pharmaceutical form: Tablet Route of administration: Oral
Pharmaceutical form: Tablet Route of administration: Oral
GI Alliance - Arizona Digestive Health - Sun City- Site Number : 8400003
Sun City, Arizona, United States
Bristol Hospital- Site Number : 8400017
Bristol, Connecticut, United States
Novum Research- Site Number : 8400018
Clermont, Florida, United States
Clinical Research of Osceola- Site Number : 8400012
Kissimmee, Florida, United States
Wellness Clinical Research - Miami Lakes - 8181 Northwest 154th Street- Site Number : 8400002
Miami Lakes, Florida, United States
Proportion of participants achieving clinical remission at Week 12 by modified Mayo Score (mMS)
Clinical remission by modified Mayo score (mMS) is defined as a mMS ≤2 with no subscore \>1 (stool frequency \[SF\] of 0 or 1 with at least a 1-point decrease from baseline, rectal bleeding \[RB\] of 0 and modified Mayo Endoscopic Subscore \[mMES\] of 0 or 1 where 1 does not include friability). Each component of the mMS (SF, RB, and mMES) is scored from 0 to 3. The total mMS ranges from 0 to 9 with higher scores indicating greater disease severity.
Time frame: Week 12
Proportion of participants achieving clinical response at Week 12 by modified Mayo Score (mMS)
Clinical response by modified Mayo score (mMS) is defined as a decrease from baseline in the mMS of ≥2 points and an improvement of ≥30% from baseline plus a decrease in rectal bleeding (RB) subscore ≥1 or an absolute RB subscore ≤1. Each component of the mMS (SF, RB, and mMES) is scored from 0 to 3. The total mMS ranges from 0 to 9 with higher scores indicating greater disease severity.
Time frame: Week 12
Proportion of participants achieving clinical response at Week 12 by full Mayo score (MS)
Clinical response by full Mayo score (MS) is defined as a decrease from baseline in the MS of ≥3 points and an improvement of ≥30% from baseline plus a decrease in rectal bleeding (RB) subscore ≥1 or an absolute RB subscore ≤1. The MS (also referred to as the full Mayo Score) is a composite index designed to measure ulcerative colitis (UC) disease activity and consists of 4 subscores: RB and SF, which are patient-reported subscores, Physician's global assessment (PGA), and endoscopic findings. Individual items are rated 0 to 3, giving the composite score a maximum of 12, with higher scores indicating greater disease severity.
Time frame: Week 12
Proportion of participants achieving clinical remission at Week 12 by full Mayo score (MS)
Clinical remission by full Mayo score (MS) is defined as a MS ≤2 with no score \>1.
Time frame: Week 12
Proportion of participants achieving the combination of patient-reported outcome 2 (PRO2) remission and endoscopic remission at Week 12
Patient-reported outcome 2 (PRO2) remission is defined as PRO2 score ≤1 with rectal bleeding (RB) of 0, and endoscopic remission is defined as mMES of 0. PRO2 score is defined as the sum of Mayo SF and RB subscores.
Time frame: Week 12
Proportion of participants achieving endoscopic remission at Week 12
Endoscopic remission is defined as mMES of 0.
Time frame: Week 12
Change from baseline in PRO2 from randomization to Week 12
PRO2 score is defined as the sum of the Mayo SF and RB subscores.
Time frame: From Baseline to Week 12
Proportion of participants achieving endoscopic response at Week 12
Endoscopic response is defined as mMES decrease of at least 1 point.
Time frame: Week 12
Proportion of participants achieving endoscopic improvement at Week 12
Endoscopic improvement is defined as mMES of 0 or 1 where 1 does not include friability.
Time frame: Week 12
Proportion of participants achieving HEMI at Week 12
Histologic endoscopic mucosal improvement (HEMI) is defined by achievement of modified Mayo endoscopic improvement (mMES of 0 or 1 where 1 does not include friability) and histological improvement (original Geboes Score \[OGS\] ≤3.1).
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
Number of participants with any treatment-emergent adverse events (TEAEs) during open-label treatment period
Time frame: From Week 12 to Week 52
Proportion achieving Inflammatory Bowel Disease Questionnaire (IBDQ) remission at Week 12
Inflammatory Bowel Disease Questionnaire (IBDQ) remission is considered as an IBDQ-32 total score ≥170 points. IBDQ is designed to capture the patient's experience of IBD on 4 domains of functioning and well-being: bowel and systemic symptoms and emotional and social function. The total IBDQ score ranges from 32 to 224 which indicates better quality of life.
Time frame: Week 12
Proportion of participants achieving Inflammatory Bowel Disease Questionnaire (IBDQ) response at Week 12
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.
Time frame: Week 12
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
GCP Clinical Research- Site Number : 8400016
Tampa, Florida, United States
GI Alliance - Glenview- Site Number : 8400005
Glenview, Illinois, United States
Illinois Gastroenterology Group- Site Number : 8400004
Gurnee, Illinois, United States
University of Michigan Health System - Ann Arbor- Site Number : 8400010
Ann Arbor, Michigan, United States
Icahn School of Medicine at Mount Sinai- Site Number : 8400001
New York, New York, United States
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