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Dose-Ranging Phase 2b Study of ABX464 in Moderate to Severe Ulcerative Colitis

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ClinicalTrials.gov Identifier: NCT03760003
Recruitment Status : Recruiting
First Posted : November 30, 2018
Last Update Posted : June 13, 2019
Sponsor:
Information provided by (Responsible Party):
Abivax S.A.

Brief Summary:
Phase IIb study to evaluate the efficacy and the safety of 3 dose-levels of ABX464, administered daily in patients with moderate to severe Ulcerative Colitis.

Condition or disease Intervention/treatment Phase
Ulcerative Colitis Drug: ABX464 25mg Drug: ABX464 50mg Drug: ABX464 100mg Drug: Placebo Phase 2

Detailed Description:

This phase IIb study will evaluate the efficacy and the safety of 3 dose-levels of ABX464, administered daily in improving Modified Mayo Score (MMS) in patients with moderate to severe Ulcerative Colitis who have inadequate response, loss of response, or intolerance with at least one of the following agents: immunosuppressant treatment (i.e. azathioprine, 6-mercaptopurine, methotrexate), tumor necrosis factor alpha [TNF-α] inhibitors, vedolizumab, JAK inhibitors and/or corticosteroid treatment .

Eligible patients will be randomized into 4 parallel intervention/treatment groups: 25mg q.d of ABX464, 50mg q.d of ABX464, 100mg q.d of ABX464, or matching placebo and will be treated for 16 weeks.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 252 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomized, double blind, placebo controlled, parallel groups
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double Blind, Placebo Controlled, Parallel Group, Multiple Dose, Induction Study to Evaluate the Safety, Tolerability and Optimal Dose of ABX464 Compared With Placebo in Patients With Moderate to Severe Ulcerative Colitis Who Have Inadequate Response, Loss of Response, or Intolerance With at Least One of the Following Agents: Immunosuppressant Treatment (i.e. Azathioprine, 6-mercaptopurine, Methotrexate), Tumor Necrosis Factor Alpha [TNF-α] Inhibitors, Vedolizumab, JAK Inhibitors and/or Corticosteroid Treatment
Actual Study Start Date : June 11, 2019
Estimated Primary Completion Date : June 30, 2020
Estimated Study Completion Date : September 30, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: ABX464
ABX464 will be administrated orally (Capsules) and daily for 16 weeks
Drug: ABX464 25mg
ABX464 25mg (One capsule of ABX464 25 mg + One capsule of placebo) once daily for 16 weeks

Drug: ABX464 50mg
ABX464 50mg (One capsule of ABX464 50 mg + One capsule of placebo) once daily for 16 weeks

Drug: ABX464 100mg
ABX464 100mg (two capsules of ABX464 50 mg) once daily for 16 weeks

Placebo Comparator: Matching Placebo
Matching placebo will be adminstrated orally (Capsules) and daily for 16 weeks
Drug: Placebo
Two capsules of placebo once daily for 16 weeks




Primary Outcome Measures :
  1. Modified Mayo Score [ Time Frame: Week 8 ]
    Reduction from baseline in Modified Mayo Score


Secondary Outcome Measures :
  1. Clinical remission [ Time Frame: Week 8 and Week 16 ]
    Clinical remission, based on the Mayo Scoring system, is defined as a rectal bleeding sub-score = 0 and an Endoscopy sub-score ≤1 (excluding friability) and at least one-point decrease in stool frequency sub score from baseline to achieve a stool frequency sub-score ≤1

  2. Endoscopic Improvement [ Time Frame: Week 8 and Week 16 ]
    Endoscopic improvement is defined as a Mayo endoscopic sub score of ≤1 (excluding friability)

  3. fecal calprotectin [ Time Frame: Week 8 and Week 16 ]
    Reduction from baseline in fecal calproctectin

  4. C Reactive Protein [ Time Frame: Week 8 and Week 16 ]
    Reduction from baseline in CRP

  5. miR-124 expression [ Time Frame: Week 8 and Week 16 ]
    Increase in miR-124 expression in Total Blood and rectal tissue

  6. Inflammatory Infiltrate [ Time Frame: Week 8 and Week 16 ]
    Inflammatory Infiltrate assessment in rectal/colon biopsies



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 Modified Mayo Score (MMS) of 4 to 9 inclusive (on a scale of 0-9). Moderate to severe active UC should be confirmed at screening visit with a centrally read endoscopy sub-score of at least 2 (on a scale of 0-3);
  • Patients having 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 immunosuppressant treatment (i.e., azathioprine, 6-mercaptopurine, methotrexate), tumor necrosis factor [TNF] inhibitors, vedolizumab, JAK inhibitors and/or corticosteroid treatment
  • Patients receiving oral corticosteroids must have been on a stable dose of prednisone or prednisone equivalent (≤16 mg/day) or on beclomethasone diproprionate (≤5mg/day) or on budesonide MMX (≤6mg/day) for at least 2 Weeks prior to the screening visit;
  • Topical corticosteroids and topical 5-aminosalicylic acid preparations must have been withdrawn at least 2 Weeks prior to the screening visit;
  • Patients who are on oral 5-aminosalicylic acid must have been on a stable dose for at least 4 Weeks prior to the screening visit;
  • Patients who are receiving immunosuppressants in the form of azathioprine, 6-mercaptopurine, or methotrexate needed to be on a stable dose for at least 4 Weeks prior to screening visit. Patients taking methotrexate also are advised to take folic acid 1 mg/day (or equivalent) supplementation if there is no contraindication;
  • Patients on probiotics (e.g., Culturelle® [Lactobacillus GG, i-Health, Inc.], Saccharomyces boulardii) must be on stable doses for at least 2 Weeks prior to the screening visit;
  • Patients on antidiarrheals (e.g., loperamide, diphenoxylate with atropine) must be on stable doses for at least 2 Weeks prior to the screening visit;
  • Patients who have received tumor necrosis factor [TNF] inhibitors, vedolizumab or other biologics must have discontinued therapy at least 8 Weeks prior to the screening visit due to lack or insufficient efficacy or intolerance;
  • Patients previously treated with cyclosporine, tacrolimus or JAK inhibitors must have discontinued therapy at least 4 Weeks prior to the screening visit due to lack or insufficient efficacy or intolerance;

Exclusion Criteria:

  • Patients with Crohn's Disease (CD) or presence or history of fistula, indeterminate colitis (IC), infectious/ischemic colitis or microscopic colitis (lymphocytic and collagenous colitis);
  • History of toxic megacolon, abdominal abscess, symptomatic colonic stricture or stoma; history or imminent colectomy, colonic malignancy;
  • History or current evidence of colonic dysplasia or adenomatous colonic polyps. Patient with severe gastrointestinal complications; e.g., short bowel syndromes, recent or planned bowel surgery, Ileostomy and/or colostomy, recent bowel perforation;
  • History of more than one episode of herpes zoster or a history (single episode) of disseminated zoster;
  • Patients with known active infections at screening such as infected abdominal abscess, Clostridium difficile (stool antigen and toxin required), CMV, TB colitis and recent infectious hospitalization;
  • Patients previously treated with ABX464;
  • Acute, chronic or history of clinically relevant pulmonary, cardiovascular, hepatic, pancreatic or renal functional abnormality, encephalopathy, neuropathy or unstable CNS pathology such as seizure disorder, angina or cardiac arrhythmias, active malignancy 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 cured (5 years disease free survivors);
  • Serious illness requiring systemic treatment and/or hospitalization within 3 Weeks prior to baseline;
  • Pregnant or breast-feeding women;
  • Illicit drug or alcohol abuse or dependence;
  • Use of any investigational or non-registered product within 3 months preceding baseline;
  • Any condition, which in the opinion of the investigator, could compromise the patient's safety or adherence to the study protocol.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03760003


Contacts
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Contact: Paul GINESTE, PhD +33 153 830 961 paul.gineste@abivax.com

Locations
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Poland
Gabinet Lekarski Prof. dr hab. med. Bartosz Korczowski Recruiting
Rzeszów, Poland
Contact: Bartosz Korczowski, Prof.         
Sponsors and Collaborators
Abivax S.A.
Investigators
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Principal Investigator: Séverine VERMEIRE, MD Universitaire Ziekenhuizen Leuven

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Responsible Party: Abivax S.A.
ClinicalTrials.gov Identifier: NCT03760003     History of Changes
Other Study ID Numbers: ABX464-103
First Posted: November 30, 2018    Key Record Dates
Last Update Posted: June 13, 2019
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Abivax S.A.:
ABX464
Refractory patients
Phase 2b
Dose Ranging
Additional relevant MeSH terms:
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Colitis
Colitis, Ulcerative
Ulcer
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Intestinal Diseases
Pathologic Processes
Inflammatory Bowel Diseases