Phase 2b/3 Study of ABX464 in Moderate to Severe Active Crohn's Disease Patients

NCT03905109 | Withdrawn Phase 2 DMC

• 1 other identifier: ABX464-201
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multicenter, randomized, placebo controlled study to evaluate the efficacy and safety of ABX464, administered once daily (QD), in inducing clinical remission and endoscopic response in patients with moderate to severe active Crohn's disease (CD) who have inadequate response, loss of response, or intolerance to prior corticosteroid and/or immunosuppressant treatment and/or biologics. This study consists of a 28 day Screening Period, a 52 week Treatment Period; including a 12 week double blinded (Cohort 1) or open label (Cohort 2) Induction Phase and a 40 week double blinded (responders) or open label (nonresponders) Maintenance Phase; and a 4 week Follow up Period, which will consist of an End of Study (EOS) visit

Conditions

Crohn Disease

Keywords

Inflammatory Bowel Disorders; ABX464

Outcome Measures

Primary Outcomes (2)

• The co-primary objectives of the study are to determine the efficacy of ABX464 in inducing clinical remission and endoscopic improvement after 12 weeks of study treatment in patients with moderate to severe active CD who have inadequate response, loss of

  Percentage of patients in clinical remission at Week 12, defined as CDAI of ≤ 150

  from baseline, at Week 12

• Co-primary objectives of the study are to determine the efficacy of ABX464 in inducing clinical remission and endoscopic improvement after 12 weeks of study treatment in patients with moderate to severe active CD who have inadequate response, loss of

  Percentage of patients with endoscopic improvement at Week 12, defined as a decrease from baseline of ≥ 50% in the global SES-CD (SES CD 50)

  from baseline, at Week 12

Secondary Outcomes (8)

• To evaluate the safety of ABX464

  from baseline, at week 12

• To evaluate the effect of ABX464 as measured by Patient-Reported-Outcome-based remission (PRO) at Week 12

  from baseline, at week 12

• To evaluate the effect of ABX464 on C reactive protein (CRP) and fecal calprotectin levels

  from baseline, at week 12

• To evaluate the effect of ABX464 on patients' quality of life

  from baseline to week 12

• To evaluate the effect of ABX464 on micro RNA (miR) 124 expression in whole blood and in tissue

  from baseline to week 12

Study Arms (3)

ABX464 dose A

EXPERIMENTAL

Dose A QD

Drug: ABX464

ABX464 Dose B

EXPERIMENTAL

Dose B QD

Drug: ABX464

Placebo

PLACEBO COMPARATOR

Matching dose

Drug: Placebo

Interventions

ABX464 DRUG

ABX464 is a new anti-inflammatory drug. In the treatment arm, patients will receive dose A or Dose B of ABX464 orally once daily for 52 weeks.

ABX464 Dose B; ABX464 dose A

Placebo DRUG

In the placebo group, patients will receive dose A or B ABX464-matching-placebo orally once daily for 52 weeks.

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men or women age 18-75 years;
• Patients must have a documented diagnosis (endoscopic with histology) of CD for ≥ 3 months before screening;
• Patients must have active moderate to severe ileal, ileocolic, or colonic CD at baseline as defined by 220 ≤ CDAI \> 450,
• Patients must have a SES-CD score \> 6 (≥4 if isolated ileal disease) at screening, assessed by ileocolonoscopy and confirmed by a central reading.
• Patients must have had either a documented inadequate response, no response, a loss of response, or an intolerance (defined as the occurrence of at least one Adverse Reaction leading to treatment discontinuation) to either amino-salicylates, immunosuppressant treatment (i.e., azathioprine, 6-mercaptopurine, methotrexate, biologics (i.e. tumor necrosis factor inhibitors, vedolizumab, ustekinumab), and/or corticosteroid treatment.
• Patients should be able and willing to comply with study visits and procedures as per protocol;
• Patients should understand, sign and date the written voluntary informed consent form at the screening visit prior to any protocol-specific procedures being performed;
• Patients should be affiliated to a social security regimen (for French sites only);
• Females and males receiving the study treatment and their partners must agree to use a highly effective contraceptive method during the study and for 3 months after end of study or early termination.

You may not qualify if:

• Patients with indeterminate colitis, microscopic colitis, ischemic colitis, infectious colitis, radiation colitis or clinical/histologic findings suggestive of ulcerative colitis;
• Patients with colonic dysplasia or neoplasia or adenomatous colonic polyp;
• Patients with presence of fistulae;
• Patients with current symptomatic diverticulitis or diverticulosis;
• Patients with obstructive colonic stricture/stenosis, past medical history of colonic resection, a history of bowel surgery within 6 months before screening, or who are likely to require surgery for CD during the treatment period;
• Patients with past medical history of clinically significant short bowel syndrome;
• Patients requiring parenteral nutrition;
• Patients with past medical history of bowel surgery resulting in an existing or current stoma;
• Patients with active infections at screening such as infected abdominal abscess, Clostridium difficile (stool antigen and toxin required), cytomegalovirus, tuberculous colitis and recent infectious hospitalization;
• Acute, chronic or history of clinically relevant pulmonary, cardiovascular, hepatic, pancreatic or renal functional abnormality, encephalopathy, neuropathy or unstable central nervous system pathology such as seizure disorder, angina or cardiac arrhythmias, or any other clinically significant medical problems as determined by physical examination and/or laboratory screening tests and/or medical history;
• Acute, chronic or history of immunodeficiency or autoimmune disease;
• History of malignancy excluding patients considered cure (5 years disease free survivors);
• Active malignancy that may require chemotherapy or radiation therapy;
• Serious illness requiring systemic treatment and/or hospitalization within 3 Weeks prior to baseline;
• Pregnant or breast-feeding woman;

Sponsors & Collaborators

• Abivax S.A.: lead

Study Sites (1)

University Hospitals Leuven - campus Gasthuisberg

Leuven, 3000, Belgium

Location

MeSH Terms

Conditions

Crohn Disease

Interventions

ABX464

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Study Officials

• Paul GINESTE, PharmD

  Abivax S.A.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-Blind Treatment
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Double-blind, placebo-controlled, randomized study

Study Record Dates

• First Submitted: April 3, 2019
• First Posted: April 5, 2019
• Study Start: September 19, 2022
• Primary Completion: September 19, 2022
• Study Completion: September 19, 2022
• Last Updated: July 31, 2024

Record last verified: 2024-07

Locations

BE (1)