Moderately to Severely Active Crohn Disease
Conditions
Keywords
Crohn Disease
Brief 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.
Interventions
DRUGObefazimod
Obefazimod is administered once-daily in fed condition (ideally at the same time in the morning).
OTHERPlacebo
Matching placebo will be administered QD in fed condition (ideally at the same time in the morning).
Sponsors
Abivax S.A.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female (at birth) 18 to 75 years old and able to understand, sign, and date the written voluntary informed consent at the visit prior to any protocol-specified procedures 2. Able and willing to comply with study visits and procedures as per protocol. 3. Confirmed and documented diagnosis of CD based on endoscopy and histology reports. 4. Moderately to severely active CD as defined by 220 ≤ CDAI ≤ 450 and SES-CD ≥ 6 for ileo-colonic or colonic disease or SES-CD ≥ 4 for isolated ileal disease (per central reading). 5. Documented inadequate response (defined as lack of response or loss of response or intolerance) to at least one of the following treatments: corticosteroids (CS), immunosuppressants (IS), biologic or biosimilar therapies, or janus kinase (JAK) (note: failure to only 5-aminosalicylic acid \[5-ASA\] is not accepted) 6. Women of childbearing potential (WOCBP) and male subjects with WOCBP partner must agree to comply with contraception requirements as stated in section 4.5 (contraception) of this protocol. 7. Subject should be affiliated to a health insurance policy whenever required by a participating country or state. 8. Subject is able and willing to comply with usual public recommendations for sun protection.
Exclusion criteria
Subjects who meet any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Induction and maintenance Phase Efficacy- Crohn's Disease Activity Index (CDAI) | Week 12 and week 52 | 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. |
| Maintenance Phase Efficacy - Simple Endoscopic Score for Crohn's disease (SES-CD) | Week 52 | 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 |
| Maintenance Phase Efficacy - Endoscopic response | Week 52 | Proportion of subjects with endoscopic response at Week 52 |
| Maintenance Phase Efficacy - SES-CD ulcer subscore > 1 | Week 52 | Proportion of subjects with no SES-CD ulcer subscore \> 1 in at least one segment at Week 52 |
| Maintenance Phase Efficacy - CDAI clinical remission | Week 52 | Proportion of subjects with CDAI clinical remission at Week 52 Proportion of subjects with sustained CDAI clinical remission at Week 52 |
| Maintenance Phase Efficacy - PRO-2 clinical remission | Week 52 | Proportion of subjects with patient reported outcome (PRO)-2 clinical remission at Week 52 |
| Maintenance Phase Efficacy - CDAI clinical response | Week 52 | Proportion of subjects with CDAI clinical response (CDAI decrease from baseline ≥ 100 points) at Week 52 |
| Maintenance Phase Efficacy - PRO-2 clinical response | Week 52 | 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 |
| Maintenance Phase Efficacy - CDAI clinical response and endoscopic response | Week 52 | Proportion of subjects with CDAI clinical response and endoscopic response at Week 52 |
| Maintenance Phase Efficacy - endoscopic remission | Week 52 | Proportion of subjects with endoscopic remission at Week 52 |
| Extension Phase Safety- Adverse events | Weeks 64, 76, 88,100 and EOS | 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 |
| Extension Phase Safety - Hematology and coagulation | Weeks 64, 76, 88,100 and EOS | 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 |
| Extension Phase Safety - Biochemistry | Weeks 64, 76, 88,100 and EOS | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Induction Phase Efficacy - SES-CD | Week 12 | Change from baseline in Simple Endoscopic Score for Crohn's disease (SES-CD) at Week 12 |
| Induction Phase Efficacy - Endoscopic response | Week 12 | Proportion of subjects with endoscopic response at Week 12 |
| Induction Phase Efficacy-SES-CD ulcer subscore > 1 | Week 12 | Proportion of subjects with no SES-CD ulcer subscore \> 1 in at least one segment at Week 12 |
| Induction Phase Efficacy-CDAI clinical remission | Week 12 | 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 |
| Induction Phase Efficacy-PRO-2 clinical remission | Week 12 | 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 |
| Induction Phase Efficacy-CDAI clinical response | Week 12 | 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 |
| Induction Phase Efficacy-PRO-2 clinical response | Week 12 | Proportion of subjects with PRO-2 clinical response at Week 12 |
| Induction Phase Efficacy-CDAI clinical response and endoscopic response | Week 12 | 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. |
| Induction Phase Efficacy - endoscopic remission | Week 12 | Proportion of subjects with endoscopic remission at Week 12 |
Countries
Belgium, Czechia, France, Germany, Hungary, Italy, Netherlands, Poland, Romania, Slovakia, Spain, United States
Contacts
CONTACTStudy Director
Outcome results
None listed