NCT03905109

Phase 2b/3 Study of ABX464 in Moderate to Severe Active Crohn's Disease Patients

Phase 2b/3, Randomized, Double Blind, Placebo Controlled Induction Phase Followed by a Maintenance Phase to Evaluate the Efficacy & Safety of ABX464 in Patients With Moderate to Severe Active Crohn's Disease & to Determine the Optimal Dose

• Status: Withdrawn
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Abivax S.A. · Industry
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

This is a multicenter, randomized, placebo controlled study to evaluate the efficacy and safety of ABX464, administered once daily (QD), in inducing clinical remission and endoscopic response in patients with moderate to severe active Crohn's disease (CD) who have inadequate response, loss of response, or intolerance to prior corticosteroid and/or immunosuppressant treatment and/or biologics. This study consists of a 28 day Screening Period, a 52 week Treatment Period; including a 12 week double blinded (Cohort 1) or open label (Cohort 2) Induction Phase and a 40 week double blinded (responders) or open label (nonresponders) Maintenance Phase; and a 4 week Follow up Period, which will consist of an End of Study (EOS) visit

Detailed description

This is a multicenter, randomized, placebo controlled study to evaluate the efficacy and safety of ABX464, administered once daily (QD), in inducing clinical remission and endoscopic response in patients with moderate to severe active Crohn's disease (CD) who have inadequate response, loss of response, or intolerance to prior corticosteroid and/or immunosuppressant treatment and/or biologics. This study consists of a 28 day Screening Period, a 52 week Treatment Period; including a 12 week double blinded (Cohort 1) or open label (Cohort 2) Induction Phase and a 40 week double blinded (responders) or open label (nonresponders) Maintenance Phase; and a 4 week Follow up Period, which will consist of an End of Study (EOS) visit Patient eligibility will be determined during a 4 week (28 days) Screening Period. Entry criteria will be based on confirmation of active moderate to severe ileal, ileocolic, or colonic CD. Approximately 930 patients will participate in this study (ABX464 Dose A N = 380, ABX464 Dose B N = 380, placebo N = 170). On Day 0, eligible patients will be randomized into 2 cohorts: * Cohort 1: Double blinded Induction Phase according to a 1:1:1 ratio into 3 treatment groups as follows: * ABX464 - Dose A QD: 170 patients * ABX464 - Dose B QD: 170 patients * Matching Placebo: 170 patients * Cohort 2: Open-label Induction Phase according to a 1:1 ratio into 2 treatment groups as follows: * ABX464 - Dose A QD: 210 patients At the end of the 12-week Induction Phase, all patients will be evaluated for the co-primary endpoints, namely induction of clinical remission and endoscopic improvement in addition to the secondary and exploratory endpoints. All patients will also be evaluated for treatment response. The determination of whether patients will be considered treatment responders versus nonresponders, responders being defined as patients with a reduction from baseline in Crohn's Disease Activity Index (CDAI) of ≥ 70 points. Patients will be allocated to the different maintenance treatment regimens according to the following rules: * Patients who received ABX464 in the Induction Phase (coming from Cohort 1 and 2) and who were responders at Week 12 will be randomized 1:1:1 to receive either ABX464 Dose A QD, ABX464 Dose B QD, or placebo in a double-blinded manner, for an additional 40 weeks. Stratification factors used for re-randomization in the Maintenance Phase are previous failure to biologics and current corticosteroid treatment use. * Patients who received ABX464 or placebo in the Induction Phase (coming from Cohort 1 and 2) but who were not responders at Week 12 will be allocated to open label ABX464 Dose A QD. They will be evaluated 12 weeks later, and they will continue only if they have achieved clinical response at that timepoint. * Patients who received placebo (coming from Cohort 1) in the Induction Phase and who were responders at Week 12 will be allocated to receive placebo as part of their double blinded maintenance treatment. At Week 24, nonresponders who received open label ABX464 Dose A QD in the Maintenance Phase will be assessed for treatment response. If patients have not achieved treatment response at Week 24, patients should discontinue study drug. All patients, including those who have had treatment response in Week 12, can be discontinued due to disease worsening. Patients will also be evaluated for safety and efficacy throughout the Induction and Maintenance Phases. From Day 0 onwards, all eligible patients will be followed at the investigational site on Week 1, Week 2, Week 4, Week 8, Week 12, and every 4 weeks until Week 52. Ileocolonoscopy will be performed in accordance with the Schedule of Activities.

Conditions

• Crohn Disease

Interventions

Type	Name	Description
DRUG	ABX464	ABX464 is a new anti-inflammatory drug. In the treatment arm, patients will receive dose A or Dose B of ABX464 orally once daily for 52 weeks.
DRUG	Placebo	In the placebo group, patients will receive dose A or B ABX464-matching-placebo orally once daily for 52 weeks.

Timeline

• Start date: 2022-09-19
• Primary completion: 2022-09-19
• Completion: 2022-09-19
• First posted: 2019-04-05
• Last updated: 2024-07-31

Locations

1 site across 1 country: Belgium