ABX464 in Subjects With Moderate to Severe Active Ulcerative Colitis

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Drug: ABX464
* Drug: Placebo oral capsule


Participation Criteria
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Eligibility Criteria
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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;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Double-blind, placebo-controlled, randomized study
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ABX464 Treatment Arm<br>Subjects will receive 50 mg of ABX464 orally once daily for 56 days. | Drug: ABX464<br>* ABX464 is a new Anti-inflammatory drug<br>|
| Placebo Comparator: ABX464 matching placebo Treatment Arm<br>Subjects will receive 50 mg of ABX464 matching Placebo orally once daily for 56 days. | Drug: Placebo oral capsule<br>* Placebo matching with ABX464<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment-emergent Adverse Events | Number of treatment-emergent adverse events in the ABX464 treated subjects compared to placebo | Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Remission | Percentage of subjects receiving ABX464 with clinical remission according to the Total Mayo Score at Week 8 compared to placebo (primary efficacy endpoint) | Week 8 | 
| Fecal Calprotectin | Percentage of patients with fecal calprotectin levels > 50µg/g at Week 8 compared to placebo | Week 8 | 
| Total Mayo Score (Ranging From 0 to 12; 12 Being the Worst Score) - 4-component Scale: Rectal Bleeding, Stool Frequency, Mucosal Appearance and Physician Global Assessment | Change from baseline in Total Mayo Score in subjects receiving ABX464 compared to placebo | Week 8 | 
| Partial Mayo Score (Ranging From 0 to 9; 9 Being the Worst Score) - 3-component Scale: Rectal Bleeding, Stool Frequency and Physician Global Assessment | Change from baseline in Partial Mayo Score in subjects receiving ABX464 at Week 4 and Week 8 compared to placebo | Week 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ABX464, Ulcerative Colitis, Refractory