A Randomized, Double-blind, Multicenter Phase III Study to Evaluate the Long-term Efficacy and Safety of ABX464 25 mg or 50 mg Once Daily as a Maintenance Therapy in Subjects With Moderately to Severely Active Ulcerative Colitis

Official Summary

This is a multicenter, randomized, placebo-controlled study to evaluate the long-term efficacy and safety of ABX464 50mg and 25mg administered once daily (QD) as maintenance therapy 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 \[biologics (TNF inhibitors, anti-integrins, anti-IL-23), and/or S1P receptor modulators, and/or JAK inhibitors\]. This study is the maintenance phase of both previous induction studies ABX464-105 and ABX464-106.

Eligibility Requirements

• Minimum Age: 16 Years

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: TRIPLE
• Enrollment: 1,116 participants

Study Arms

• ABX464 50mg - Responder subjects at the end of induction (PLACEBO_COMPARATOR)
  Subjects will be orally dosed during 44 weeks
• ABX464 25mg - Responder subjects at the end of induction (PLACEBO_COMPARATOR)
  Subjects will be orally dosed during 44 weeks
• Placebo - Responder subjects at the end of induction (PLACEBO_COMPARATOR)
  Subjects will be orally dosed during 44 weeks
• ABX464 50mg - Non responder subjects at the end of induction (EXPERIMENTAL)
  Subjects will be orally dosed during 44 weeks
• ABX464 25mg - Non responder subjects at the end of induction (EXPERIMENTAL)
  Subjects will be orally dosed during 44 weeks
• Long Term Extension (EXPERIMENTAL)
  At the end of the maintenance phase (week 44), subjects can continue their allocated treatment for up to 4 years. Once the maintenance phase is unblinded, subjects receiving placebo in the maintenance phase will be allocated to obefazimod 25 mg or can terminate the study.

Interventions

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

Primary Outcomes

• Rate of subjects in clinical remission at Week 44 (Week 44)
• Number and percentage of all treatment-emergent adverse events (TEAEs) (Week 44)
• Number and percentage of all serious adverse events (SAEs) (Week 44)
• Number and percentage of all causally related TEAEs/SAEs (Week 44)

Secondary Outcomes

• Proportion of subjects with endoscopic improvement at Week 44 (Week 44)
• Proportion of subjects with corticosteroid-free clinical remission (Week 44)
• Proportion of subjects with sustained clinical remission at Week 44 (Week 44)
• Proportion of subjects with HEMI per Geboes scoring at Week 44 (Week 44)
• Proportion of subjects with endoscopic remission at Week 44 (Week 44)

Eligibility Criteria

Inclusion Criteria in maintenance phase:

* Subjects must have completed the induction treatment study (ABX464-105 or ABX464-106), and patients' clinical response status must be available.
* Subjects with a valid endoscopy performed at the end of the induction study and results from central reader available at Day 1.
* 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.
* Women of childbearing potential (WOCBP) subjects and male subjects with WOCBP partner must agree to comply with contraception requirements as described in Section 4.4. (Contraception) of the protocol.
* Subjects must be 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

Inclusion criteria in LTE phase:

* Subject must have completed the maintenance phase
* Investigator and subject must assess and agree that the subject has received, and will continue to receive benefit from being in the study

Exclusion Criteria in maintenance phase:

* Subjects who permanently discontinued the study treatment during the induction study (either ABX464-105 or ABX464-106).
* Subjects who have developed any major illness/condition (eg. primary sclerosis cholangitis, Crohn's disease, colectomy, diverting ileostomy, colon cancer or colonic adenomas \[low or high grade dysplasia\]).
* Subjects with evidence of an unstable clinical condition (eg. toxic megacolon, fulminant colitis, bowel perforation, uncontrolled ischemic disease, congestive heart failure with NYHA class 3 or 4 symptoms) during the induction study that, in the investigator's judgment, will substantially increase the risk to the subject if he or she participates in the study.
* Subjects who plan to participate in other investigational studies during the maintenance study.
* Male or female planning a pregnancy, or pregnant female subjects
* Introduction during induction study of prohibited medications, dosages, surgical or non-medicinal procedures indicated for UC (except antidiarrheals and motility agents for acute diarrhea).
* Any changes in the laboratory values during the induction period that could jeopardize subject's safety in the opinion of the investigator. If any doubts, the investigator should contact the sponsor study medical monitor.
* Subject who is planning to receive live vaccine during the study.
* Subjects committed to an institution by virtue of an order issued either by the judicial or the administrative authorities.

Exclusion criteria for LTE phase:

* Subject continues to satisfy exclusion criteria listed above for the maintenance phase
* Introduction during maintenance phase of prohibited medications, dosages, surgical or non-medicinal procedures indicated for UC (except antidiarrheals and motility agents for acute diarrhea).

Trial Locations

• University of Alabama -Birmingham, Birmingham, Alabama, United States
• Digestive Health Specialists of the Southeast, Dothan, Alabama, United States
• Lakeview Clinical Research, Guntersville, Alabama, United States
• Research Solutions of Arizona, PC, Litchfield Park, Arizona, United States
• Valleywise Health Medical Center, Phoenix, Arizona, United States
• GI Alliance, Sun City, Arizona, United States
• Del Sol Research Management, LLC, Tucson, Arizona, United States
• University of Arizona, Tucson, Arizona, United States
• University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States
• Applied Research Center of Arkansas, Little Rock, Arkansas, United States
• ...and 10 more locations

Study Officials

• Severine Vermeire, MD, PhD — PRINCIPAL_INVESTIGATOR
  UZ Leuven, Belgium
• Bruce Sands, MD, PhD — PRINCIPAL_INVESTIGATOR
  Mount Sinai Health System Digestive Disease Institute, New York USA

More Ulcerative Colitis Trials

View all Ulcerative Colitis clinical trials