ABX464 in Subjects With Moderate to Severe Active Ulcerative Colitis

Ulcerative Colitis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03093259
• Other study ID #: ABX464-101
• Status: Completed
• Phase: Phase 2
• Start date: November 16, 2017
• Est. completion date: February 4, 2019

Study information

• Verified date: May 2022
• Source: Abivax S.A.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: February 4, 2019
• Est. primary completion date: July 25, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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;

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer
• Ulcerative Colitis

Intervention

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

Locations

Country	Name	City	State
Austria	Univ.-Klinik für Innere Medizin I	Innsbruck
Belgium	University Hospitals Leuven - campus Gasthuisberg	Leuven
Czechia	Klinické centrum ISCARE	Praha
Czechia	Orlicko-ustecka nemocnice	Ústí Nad Orlicí
France	CHRU de Lille	Lille
France	CHU de Nantes	Nantes
France	CHU de Nice	Nice
France	CHU Saint Etienne - CHU Hopital Nord	St Priest en Jarez
Germany	Medizinische Klinik für Gastroenterologie, Infektiologie und Rheumatologie	Berlin
Germany	Akademisches Lehrkrankenhaus Christian-Albrechts-Universität zu Kiel	Hamburg
Hungary	DRC Gyógyszervizsgáló Központ Kft	Balatonfüred
Hungary	Belgyógyászati Klinika	Budapest
Hungary	Vasútegészségügyi Nonprofit Közhasznú Kft.,	Debrecen
Poland	Centrum Badan	Lódz
Poland	KO-Med	Lublin
Poland	Medpolonia Poznan	Poznan
Poland	NZOZ ViVamed	Warsaw
Poland	Centrum Badan Klinicznych Lekarze Sp.p	Wroclaw
Spain	Hospital RAMÓN Y CAJAL	Madrid

Sponsors (1)

Lead Sponsor	Collaborator
Abivax S.A.

Countries where clinical trial is conducted

Austria,  Belgium,  Czechia,  France,  Germany,  Hungary,  Poland,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Subjects With Treatment-emergent Adverse Events	Number of treatment-emergent adverse events in the ABX464 treated subjects compared to placebo	Week 8
Secondary	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
Secondary	Fecal Calprotectin	Percentage of patients with fecal calprotectin levels > 50µg/g at Week 8 compared to placebo	Week 8
Secondary	Total Mayo Score	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	Week 8
Secondary	Change in Partial Mayo Score	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.	Week 8