Clinical trial NCT03093259: ABX464 in Subjects With Moderate to Severe Active Ulcerative Colitis
Official title: Phase IIa Study to Evaluate the Safety and Efficacy of ABX464 Versus Placebo in Subjects With Moderate to Severe Active Ulcerative Colitis Who Have Failed or Are Intolerant to Immunomodulators, Anti-TNFα, Vedolizumab and/or Corticosteroids
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ulcerative Colitis
Keywords: ABX464
Ulcerative Colitis
Refractory
Lead sponsor: Abivax S.A.
Sponsor class: INDUSTRY
First posted: 2017-03-28
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double-blind, placebo-controlled, randomized study
Primary purpose: TREATMENT

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.

Eligibility criteria: 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).

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;

Primary outcomes:
measure: Number of Subjects With Treatment-emergent Adverse Events
timeFrame: Week 8
Secondary outcomes:
measure: Clinical Remission
timeFrame: Week 8
measure: Fecal Calprotectin
timeFrame: Week 8
measure: Total Mayo Score
timeFrame: Week 8
measure: Change in Partial Mayo Score
timeFrame: Week 8
Other outcomes:
Locations:
city: Innsbruck
country: Austria
facility: Univ.-Klinik für Innere Medizin I
city: Leuven
country: Belgium
facility: University Hospitals Leuven - campus Gasthuisberg
city: Praha
country: Czechia
facility: Klinické centrum ISCARE
city: Ústí Nad Orlicí
country: Czechia
facility: Orlicko-ustecka nemocnice
city: Lille
country: France
facility: CHRU de Lille
city: Nantes
country: France
facility: CHU de Nantes
city: Nice
country: France
facility: CHU de Nice
city: St Priest en Jarez
country: France
facility: CHU Saint Etienne - CHU Hopital Nord
city: Berlin
country: Germany
facility: Medizinische Klinik für Gastroenterologie, Infektiologie und Rheumatologie
city: Hamburg
country: Germany
facility: Akademisches Lehrkrankenhaus Christian-Albrechts-Universität zu Kiel
city: Balatonfüred
country: Hungary
facility: DRC Gyógyszervizsgáló Központ Kft
city: Budapest
country: Hungary
facility: Belgyógyászati Klinika
city: Debrecen
country: Hungary
facility: Vasútegészségügyi Nonprofit Közhasznú Kft.,
city: Lublin
country: Poland
facility: KO-Med
city: Poznań
country: Poland
facility: Medpolonia Poznań
city: Warsaw
country: Poland
facility: NZOZ ViVamed
city: Wrocław
country: Poland
facility: Centrum Badań Klinicznych Lekarze Sp.p
city: Łódź
country: Poland
facility: Centrum Badań
city: Madrid
country: Spain
facility: Hospital RAMÓN Y CAJAL
Study officials:
References: