A Randomized, Double-blind, Placebo-controlled, Multicenter Phase III Study to Evaluate the Efficacy and Safety of ABX464 Once Daily for Induction Treatment in Subjects With Moderately to Severely Active Ulcerative Colitis

Official Summary

This is a multicenter, randomized, placebo controlled study to evaluate the efficacy and safety of ABX464 given at 25 or 50 mg QD in inducing clinical remission in subjects with moderately to severely active ulcerative colitis who have inadequate response, no response, a loss of response, or an intolerance to either conventional therapies \[corticosteroids, immunosuppressant (i.e. azathioprine, 6-mercaptopurine, methotrexate)\] and/or advanced therapies \[biologics (TNF inhibitors, anti-integrins, anti-IL-23), and/or S1P receptor modulators, and/or JAK inhibitors\].

Eligibility Requirements

• Minimum Age: 16 Years

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: TRIPLE
• Enrollment: 639 participants

Study Arms

• ABX464 50mg (EXPERIMENTAL)
  Subjects will be orally dosed daily in a fed condition ideally at the same time in the morning) for 8 weeks
• ABX464 25mg (EXPERIMENTAL)
  Subjects will be orally dosed daily in a fed condition ideally at the same time in the morning) for 8 weeks
• Placebo (PLACEBO_COMPARATOR)
  Subjects will be orally dosed daily in a fed condition ideally at the same time in the morning) for 8 weeks

Interventions

• DRUG: ABX464 — Administered once daily in the morning with food
• DRUG: Placebo — Administered once daily in the morning with food

Primary Outcomes

• Proportion of subjects who achieve clinical remission per Modified Mayo Score at week 8 (8 weeks)

Secondary Outcomes

• Proportion of subjects who achieve endoscopic improvement at week 8 (8 weeks)
• Proportion of subjects who achieve clinical response per MMS at week 8 (8 weeks)
• Proportion of subjects with symptomatic remission at week 8 (8 weeks)
• Proportion of subjects with HEMI per Geboes at week 8 (8 weeks)

Eligibility Criteria

Inclusion Criteria:

* Men or women at least 16 years old; Adolescent subjects will only be enrolled if approved by the country regulatory/health authority. If these approvals have not been granted, only subjects ≥ 18 years old will be enrolled. To be eligible, adolescent subjects must weight ≥ 40 kg and meet the definition of Tanner Stage 5 at the screening visit.
* Subjects must understand, sign and date the written voluntary informed consent form at the visit prior to any protocol-specific procedures. For under-aged subjects, national requirements regarding consent should also be met.
* Documented diagnosis of UC confirmed by endoscopy and histology. Should endoscopy/histology results not be available at screening, results from endoscopies or biopsies taken at screening may be used.
* Active disease defined by modified Mayo score (MMS) ≥ 5 with rectal bleeding subscore (RBS) ≥ 1 and endoscopy subscore (MES) of 2 or 3 (confirmed by central reader).
* Subjects with documented inadequate response (defined as lack of response or loss of response or intolerance) to at least one of the following treatments: corticosteroids, immunosuppressant, biologic or biosimilar therapies, S1P receptor modulators and/or JAK inhibitors and/or new drugs approved during the study (note: failure to only 5-ASA or sulfasalazine is not accepted).
* Women of childbearing potential (WOCBP) subjects and male subjects with WOCBP partner must agree to comply with the contraception requirements described in the protocol.
* Subjects able and willing to comply with study visits and procedures as per protocol.
* Subjects should be affiliated to a health insurance policy whenever required by a participating country or state.

Exclusion Criteria:

* Subjects with UC limited to an isolated proctitis (≤ 15cm from anal verge) determined by endoscopy central reading.
* Subjects with primary sclerosing cholangitis or autoimmune hepatitis.
* Subjects who have failed on 5-ASA or sulfasalazine therapy only.
* Subjects with CD or presence or history of fistula, indeterminate colitis, infectious/ischemic colitis or microscopic colitis (lymphocytic and collagenous colitis).
* History or current evidence of toxic megacolon, fulminant colitis, bowel perforation.
* History of colonic cancer or colonic low grade or high grade dysplasia adenomatous polyps, and/or at the screening endoscopy, evidence of colonic cancer or evidence of low grade or high grade dysplasia adenomatous polyps (fully removed or not).
* Recent or planned bowel surgery or history of proctocolectomy or partial colectomy or current stoma.
* Subjects on antidiarrheals including those working on motility (e.g., loperamide, diphenoxylate with atropine, etc.).
* Subjects on probiotics (e.g., Culturelle® \[Lactobacillus GG, i-Health, Inc.\], Saccharomyces boulardii).
* Subjects who do not meet the washout period requirements prior to the screening endoscopy
* Subjects with the following hematological and biochemical laboratory parameters obtained during the screening period:

  * Hemoglobin ≤ 8.0 g dL-1
  * Absolute neutrophil count \< 750 mm-3
  * Platelets \< 100,000 mm-3
  * Creatinine clearance \< 60 mL.min-1 (Cockroft-Gault formula)
  * Total serum bilirubin \> 1.5 x ULN
  * Alkaline phosphatase, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \> 2 x ULN
* Subjects with the following conditions (infection):

  * Subjects with chronic or recurrent grade 3 or grade 4 infection within the last 2 months prior to screening or a history of opportunistic infection while not on immunosuppressive therapy.
  * Herpes zoster reactivation within the last 2 months prior to screening.
  * Subjects with active infection at screening or any major episode of infection that required hospitalization or treatment with intravenous antibiotics within 1 month of screening or during screening. Fungal infection of nail beds is allowed.
  * Positive assay or stool culture for pathogens (ova and parasite examination, bacteria) or positive test for Clostridium difficile toxin at screening. If C. difficile is positive, subject may be treated and retested ≥ 2 weeks after completing treatment.
  * Subjects with HIV infection.
  * Subjects having acute or chronic hepatitis B infection at screening (positive for hepatitis B surface antigen \[HbsAg\], or negative for HbsAg and positive for anti-hepatitis B core antibody in conjunction with detectable HBV DNA, or detectable HBV DNA).
  * Subjects having acute or chronic hepatitis C infection at screening as defined by positive for hepatitis C antibody (subjects successfully treated and without recurrence ≥ 1 year with no detectable HCV RNA \[assessed centrally\] are eligible).
  * Active tuberculosis (TB) or untreated latent TB are ruled out. For subjects with positive or intermediate QuantiFERON test see study protocol.
* Subjects with an uncontrolled ischemic heart disease and/or a history of congestive heart failure with New York Heart Association (

Trial Locations

• Digestive Health Specialists of the Southeast, Dothan, Alabama, United States
• Lakeview Clinical Research, Guntersville, Alabama, United States
• GI Alliance, Sun City, Arizona, United States
• Del Sol Research Management, LLC, Tucson, Arizona, United States
• University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States
• Aurora Care Clinic, Costa Mesa, California, United States
• Gastro Care Institute, Lancaster, California, United States
• California Medical Research Associates Inc., Northridge, California, United States
• Clinnova Research Solutions, Orange, California, United States
• Peak Gastroenterology Associates, Colorado Springs, Colorado, United States
• ...and 10 more locations

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