ABX464 in Subjects With Moderate to Severe Active Ulcerative Colitis

Phase 2

Completed

• Conditions: Ulcerative Colitis
• Interventions: Drug: Placebo oral capsule; Drug: ABX464

• Registration Number: NCT03093259
• Lead Sponsor: Abivax S.A.

Brief Summary

This Phase IIa study is an 8-week, double-blind, placebo-controlled, randomized study aiming at evaluating the safety and the efficacy of ABX464 given once a day (o.d) at 50 mg in subjects with moderate to severe Active Ulcerative Colitis who have failed or are intolerant to immunomodulators, Anti-TNFα, vedolizumab and/or corticosteroids followed by a one-month follow-up period.

Detailed Description

This Phase IIa study is an 8-week, double-blind, placebo-controlled, randomized study aiming at evaluating the safety and the efficacy of ABX464 given once a day (o.d) at 50 mg in subjects with moderate to severe Active Ulcerative Colitis who have failed or are intolerant to immunomodulators, Anti-TNFα, vedolizumab and/or corticosteroids followed by a one-month follow-up period.

Eligible subjects will be randomized according to a 2/1 ratio in two different groups of treatment. Randomized subjects who will receive 50 mg ABX464 orally once daily for 56 days.

Study Timeline

• Study First Submitted: 2017-03-17
• Study First Submitted QC: 2017-03-22
• Study First Posted: 2017-03-28
• Study Start: 2017-11-16
• Primary Completion: 2018-07-25
• Study Completion: 2019-02-04
• Results First Submitted: 2021-10-14
• Status Verified: 2022-05
• Results First Submitted QC: 2022-05-09
• Results First Posted: 2023-02-08
• Last Update Submitted: 2024-05-16
• Last Update Posted: 2024-06-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 32

Inclusion Criteria

• Diagnosis of moderate to severe active UC confirmed by endoscopy and histology at least 12 weeks prior to screening visit. Moderate to severe active UC defined by Mayo Clinic Score (MCS) of 6 to 12 inclusive (on a scale of 0-12). Moderate to severe active UC should be confirmed at screening visit with a centrally read MCS endoscopy score of at least 2 (on a scale of 0-3);
• Subjects receiving oral corticosteroids must have been on a stable dose of prednisone or prednisone equivalent ≤20 mg/day) or on beclomethasone diproprionate (≤5mg/day) or on budesonide MMX (≤9mg/day), for ≥2 weeks before first dosing (i.e. baseline);
• Topical corticosteroids and topical 5-aminosalicylic acid preparations must have been withdrawn ≥2 weeks before first dosing (i.e. baseline);
• Subjects who are on oral 5-aminosalicylic acid must have been on a stable dose ≥4 weeks before first dosing (i.e. baseline);
• Subjects who are receiving immunosuppressants in the form of azathioprine, 6-mercaptopurine, or methotrexate needed to be on a stable dose for 4 weeks before first dosing (i.e. baseline). Subjects taking methotrexate also are advised to take folic acid 1 mg/day (or equivalent) supplementation if there is no contraindication;
• Subjects on probiotics (e.g., Culturelle® [Lactobacillus GG, i-Health, Inc.], Saccharomyces boulardii) must be on stable doses for 2 weeks before first dosing (i.e. baseline);
• Subjects on antidiarrheals (e.g., loperamide, diphenoxylate with atropine) must be on stable doses for 2 weeks before first dosing (i.e. baseline);
• Subjects who have previously received anti-tumor necrosis factor (TNF) therapy or vedolizumab must have discontinued therapy ≥8 weeks before first dosing (i.e. baseline);
• Subjects previously treated with cyclosporine or tacrolimus must have discontinued therapy ≥4 weeks before first dosing (i.e. baseline);
• Subjects previously treated with tube feeding, defined formula diets, or parenteral alimentation/nutrition must have discontinued treatment 3 weeks before first dosing (i.e. baseline).

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Exclusion Criteria

• Subject with Crohn's Disease (CD), indeterminate colitis (IC) or presence or history of fistula with CD;
• History of toxic megacolon, abdominal abscess, symptomatic colonic stricture or stoma; history or is at imminent risk of colectomy;
• History or current evidence of colonic dysplasia or adenomatous colonic polyps. Subject with severe gastrointestinal complications; e.g., short bowel syndromes, obstructing strictures, recent or planned bowel surgery, Ileostomy and/or colostomy, recent bowel perforation;
• Subject with significant and known active infections at screening such as Infected abscess, positive for Clostridium difficile (stool antigen and toxin), CMV, TB and recent infectious hospitalization;

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ABX464 matching placebo Treatment Arm	Placebo oral capsule	Subjects will receive 50 mg of ABX464 matching Placebo orally once daily for 56 days.
ABX464 Treatment Arm	ABX464	Subjects will receive 50 mg of ABX464 orally once daily for 56 days.

Primary Outcome Measures

Name	Time	Method
Number of Subjects With Treatment-emergent Adverse Events	Week 8	Number of treatment-emergent adverse events in the ABX464 treated subjects compared to placebo

Secondary Outcome Measures

Name	Time	Method
Clinical Remission	Week 8	Percentage of subjects receiving ABX464 with clinical remission according to the Total Mayo Score at Week 8 compared to placebo (primary efficacy endpoint)
Fecal Calprotectin	Week 8	Percentage of patients with fecal calprotectin levels \> 50µg/g at Week 8 compared to placebo
Change in Partial Mayo Score	Week 8	Change from baseline in Partial Mayo Score in subjects receiving ABX464 compared to placebo. The scale ranges from 0 to 9, with 9 indicating the worst score. It is a three-component scale assessing rectal bleeding, stool frequency, and the physician's global assessment.
Total Mayo Score	Week 8	Change from baseline in Total Mayo Score in subjects receiving ABX464 compared to placebo. The scale ranges from 0 to 12; 12 being the worst score) - 4-component Scale: Rectal bleeding, Stool frequency, Mucosal appearance and Physician Global Assessment

Trial Locations

Locations (19)

Univ.-Klinik für Innere Medizin I; 🇦🇹 Innsbruck, Austria

Klinické centrum ISCARE; 🇨🇿 Praha, Czechia

CHU de Nantes; 🇫🇷 Nantes, France

CHRU de Lille; 🇫🇷 Lille, France

Orlicko-ustecka nemocnice; 🇨🇿 Ústí Nad Orlicí, Czechia

CHU de Nice; 🇫🇷 Nice, France

CHU Saint Etienne - CHU Hopital Nord; 🇫🇷 St Priest en Jarez, France

Medizinische Klinik für Gastroenterologie, Infektiologie und Rheumatologie; 🇩🇪 Berlin, Germany

Akademisches Lehrkrankenhaus Christian-Albrechts-Universität zu Kiel; 🇩🇪 Hamburg, Germany

NZOZ ViVamed; 🇵🇱 Warsaw, Poland

Hospital RAMÓN Y CAJAL; 🇪🇸 Madrid, Spain

KO-Med; 🇵🇱 Lublin, Poland

Medpolonia Poznań; 🇵🇱 Poznań, Poland

Belgyógyászati Klinika; 🇭🇺 Budapest, Hungary

University Hospitals Leuven - campus Gasthuisberg; 🇧🇪 Leuven, Belgium

DRC Gyógyszervizsgáló Központ Kft; 🇭🇺 Balatonfüred, Hungary

Centrum Badań Klinicznych Lekarze Sp.p; 🇵🇱 Wrocław, Poland

Vasútegészségügyi Nonprofit Közhasznú Kft.,; 🇭🇺 Debrecen, Hungary

Centrum Badań; 🇵🇱 Łódź, Poland