ABX464 in Subjects With Moderate to Severe Active Ulcerative Colitis

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.

• ABX464 (Drug): ABX464 is a new Anti-inflammatory drug
• Placebo oral capsule (Drug): Placebo matching with ABX464

Primary outcomes

• 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 outcomes

• 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
• 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
• 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.

Sex: All, ages: 18 Years to 70 Years

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;

Participant flow

Outcome results

• Number of Subjects With Treatment-emergent Adverse Events (Primary), Count of participants, Participants: ABX464 Treatment Arm 18; ABX464 Matching Placebo Treatment Arm 5 (p 0.2096)
• Clinical Remission (Secondary), Count of participants, Participants: ABX464 Matching Placebo Treatment Arm 7; ABX464 Treatment Arm 1 (p 0.1588)
• Fecal Calprotectin (Secondary), Count of participants, Participants: ABX464 Treatment Arm 15; ABX464 Matching Placebo Treatment Arm 8 (p 0.4830)
• Total Mayo Score (Secondary), Mean, score on a scale: ABX464 Treatment Arm -4.6 +/- 2.8; ABX464 Matching Placebo Treatment Arm -2.1 +/- 2.5 (p 0.0742)
• Change in Partial Mayo Score (Secondary), Mean, units on a scale: ABX464 Treatment Arm -3.9 +/- 2.2; ABX464 Matching Placebo Treatment Arm -1.8 +/- 2.0 (p 0.0462)

Adverse events

Time frame: From baseline up to 4 weeks post last dose of study drug (up to 63 Days)

Serious adverse events by term

Other adverse events by term

• Study Protocol (PDF, 2018-03-13)
• Statistical Analysis Plan (PDF, 2018-08-23)