ABX464 in Subjects With Moderate to Severe Active Ulcerative Colitis
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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 Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: ABX464 Treatment Arm Subjects will receive 50 mg of ABX464 orally once daily for 56 days. |
Drug: ABX464
ABX464 is a new Anti-inflammatory drug
|
| Placebo Comparator: ABX464 matching placebo Treatment Arm Subjects will receive 50 mg of ABX464 matching Placebo orally once daily for 56 days. |
Drug: Placebo oral capsule
Placebo matching with ABX464
|
Outcome Measures
Primary Outcome Measures
- Number of incidences of treatment-emergent adverse events [Through study completion, an average of 12 weeks]
Number of incidences of treatment-emergent adverse events in the ABX464 treated subjects compared to placebo
Secondary Outcome Measures
- IL-22 expression levels [Week 4 and Week 8]
Change from baseline in IL-22 expression levels (transcriptome) in serum and rectal/sigmoidal tissue compared to placebo
- MicroRNA-124 levels [Week 4 and Week 8]
Change from baseline in microRNA-124 levels in whole blood (PAXgene®) compared to placebo.
- Total Mayo Score [Week 4 and Week 8]
Change from baseline in Total Mayo Score in subjects receiving ABX464 compared to placebo
- Clinical Remission according to the Total Mayo Score [Week 4 and Week 8]
Proportion of subjects receiving ABX464 with clinical remission according to the Total Mayo Score compared to placebo. Remission exclude friability and is based on total Mayo score ≤ 2 with no individual sub-score > 1
Eligibility Criteria
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);
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Subjects who are on oral 5-aminosalicylic acid must have been on a stable dose ≥4 weeks before first dosing (i.e. baseline);
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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);
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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);
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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;
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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;
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University Hospitals Leuven - campus Gasthuisberg | Leuven | Belgium | 3000 |
Sponsors and Collaborators
- Abivax S.A.
Investigators
- Study Director: Paul GINESTE, Abivax S.A.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ABX464-101