Efficacy and Safety of Obefazimod in Subjects With Moderately to Severely Active Crohn's Disease
NCT Number: NCT06456593
Acronym: ENHANCE-CD
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Moderately to Severely Active Crohn Disease
Interventions: DRUG: Obefazimod|OTHER: Placebo
Sponsor: Abivax S.A.
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 212
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: QUADRUPLE (PARTICIPANT, CARE_PROVIDER, INVESTIGATOR, OUTCOMES_ASSESSOR)|Primary Purpose: TREATMENT
Start Date: 2024-09
Completion Date: 2028-04

Summary:
This study has 3 treatment phases, a 12-Week Induction Phase, a 40-Week Maintenance Phase, and a 48-Week Extension Phase.

The objective is to evaluate the efficacy and safety of obefazimod compared to placebo as induction and maintenance therapy in subjects with moderately to severely active CD after inadequate response (no response, loss of response, or intolerance) to conventional therapies and/or advanced therapies.

The primary objective for the 48-Week Extension Phase is to evaluate the safety and tolerability of obefazimod compared with placebo in subjects who are enrolled in the Extension Phase.

Primary Outcome Measures: Induction and maintenance Phase Efficacy- Crohn's Disease Activity Index (CDAI), Change from baseline in Crohn's Disease Activity Index (CDAI) score at Week 12 and Week 52 The CDAI total score ranges from 0 to over 600. Higher scores mean a worse outcome., Week 12 and week 52|Maintenance Phase Efficacy - Simple Endoscopic Score for Crohn's disease (SES-CD), Change from baseline in Simple Endoscopic Score for Crohn's disease (SES-CD) at Week 52

The SES-CD is an endoscopic grading system that consists of a composite score based on 4 components: the size of mucosal ulcers, the extent of the ulcerated surface, the endoscopic extension, and the presence of stenosis (26). Each of the 4 SES-CD components are assessed in the 5 segments of the ileum and colon: ileum, right, transverse, left, and rectum. The SES-CD is the sum of the individual scores of each of the components across the 5 segments. The total score ranges from 0 to 60. Higher scores mean a worse outcome, Week 52|Maintenance Phase Efficacy - Endoscopic response, Proportion of subjects with endoscopic response at Week 52, Week 52|Maintenance Phase Efficacy - SES-CD ulcer subscore > 1, Proportion of subjects with no SES-CD ulcer subscore \> 1 in at least one segment at Week 52, Week 52|Maintenance Phase Efficacy - CDAI clinical remission, Proportion of subjects with CDAI clinical remission at Week 52 Proportion of subjects with sustained CDAI clinical remission at Week 52, Week 52|Maintenance Phase Efficacy - PRO-2 clinical remission, Proportion of subjects with patient reported outcome (PRO)-2 clinical remission at Week 52, Week 52|Maintenance Phase Efficacy - CDAI clinical response, Proportion of subjects with CDAI clinical response (CDAI decrease from baseline ≥ 100 points) at Week 52, Week 52|Maintenance Phase Efficacy - PRO-2 clinical response, Proportion of subjects with PRO-2 clinical response (≥ 30% decrease in average daily PRO-2 score (AP + SF) and both no higher than baseline) at Week 52, Week 52|Maintenance Phase Efficacy - CDAI clinical response and endoscopic response, Proportion of subjects with CDAI clinical response and endoscopic response at Week 52, Week 52|Maintenance Phase Efficacy - endoscopic remission, Proportion of subjects with endoscopic remission at Week 52, Week 52|Extension Phase Safety- Adverse events, Incidence of all treatment-emergent adverse events (TEAEs), serious adverse events (SAEs) and causally related TEAEs/SAEs Incidence of adverse events (AEs) leading to discontinuation, Weeks 64, 76, 88,100 and EOS|Extension Phase Safety - Hematology and coagulation, Number of patients with clinically-significant abnormal laboratory parameters. Hematology: Hematocrit, hemoglobin, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, mean corpuscular volume, platelet count, red blood cells; white blood cells Coagulation: International normalized ratio, activated partial thromboplastin time, fibrinogen, prothrombin time, Weeks 64, 76, 88,100 and EOS|Extension Phase Safety - Biochemistry, Number of patients with clinically-significant abnormal laboratory parameters. Albumin, total protein, aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), total bilirubin, gamma glutamyl transferase (GGT), lactate dehydrogenase (LDH), lipase, amylase, creatinine, creatinine clearance, urea, chloride, bicarbonate, sodium, potassium, calcium, phosphate, uric acid, glucose, total cholesterol, LDL cholesterol (direct), HDL cholesterol, triglycerides, creatine phosphokinase (CPK), high sensitivity troponin I and T, N-terminal prohormone of brain natriuretic peptide (NT-proBNP), Weeks 64, 76, 88,100 and EOS
Secondary Outcome Measures: Induction Phase Efficacy - SES-CD, Change from baseline in Simple Endoscopic Score for Crohn's disease (SES-CD) at Week 12, Week 12|Induction Phase Efficacy - Endoscopic response, Proportion of subjects with endoscopic response at Week 12, Week 12|Induction Phase Efficacy-SES-CD ulcer subscore > 1, Proportion of subjects with no SES-CD ulcer subscore \> 1 in at least one segment at Week 12, Week 12|Induction Phase Efficacy-CDAI clinical remission, Proportion of subjects with Crohn's Disease Activity Index (CDAI) clinical remission (CDAI score \< 150) at Week 12 The total CDAI score ranges from 0 to over 600. Higher scores mean a worse outcome, Week 12|Induction Phase Efficacy-PRO-2 clinical remission, Proportion of subjects with patient reported outcome (PRO)-2 clinical remission (Combination of average daily abdominal pain score ≤ 1.0 plus average daily soft or liquid stool frequency ≤ 2.8 and both no higher than baseline) at Week 12, Week 12|Induction Phase Efficacy-CDAI clinical response, Proportion of subjects with CDAI clinical response (CDAI decrease from baseline ≥ 100 points) at Week 12 The total CDAI score ranges from 0 to over 600. Higher scores mean a worse outcome, Week 12|Induction Phase Efficacy-PRO-2 clinical response, Proportion of subjects with PRO-2 clinical response at Week 12, Week 12|Induction Phase Efficacy-CDAI clinical response and endoscopic response, Proportion of subjects with CDAI clinical response (CDAI decrease from baseline ≥ 100 points) and endoscopic response (Simple Endoscopic Score for Crohn's disease (SES-CD) decrease from baseline ≥ 50%) at Week 12

The total CDAI score ranges from 0 to over 600. Higher scores mean a worse outcome The total SES-CD score ranges from 0 to 60. Higher scores mean a worse outcome., Week 12|Induction Phase Efficacy - endoscopic remission, Proportion of subjects with endoscopic remission at Week 12, Week 12