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

• Register: ClinicalTrials.gov
• Last refreshed on: 10 August 2021
• Main ID: NCT03760003
• Date of registration: 29/11/2018
• Prospective Registration: Yes
• Primary sponsor: Abivax S.A.
• Public title: Dose-Ranging Phase 2b Study of ABX464 in Moderate to Severe Ulcerative Colitis
• Scientific 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-a] Inhibitors, Vedolizumab, JAK Inhibitors and/or Corticosteroid Treatment
• Date of first enrolment: September 23, 2019
• Target sample size: 254
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03760003
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 2

Countries of recruitment

Austria, Belarus, Belgium, Canada, Czechia, France, Germany, Hungary, Italy, Poland, Serbia, Slovakia, Slovenia, Spain, Ukraine, United Kingdom, United States

Contacts

• Name: Séverine VERMEIRE, MD
• Affiliation: Universitaire Ziekenhuizen Leuven

Key inclusion & exclusion criteria

Inclusion Criteria:

- Men or women age 18 - 75 years;

- Diagnosis of moderate to severe active UC (including ulcerative proctitis if proximal
extension of disease occurs beyond 10 cm) 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 5 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. Inadequate
response, no response, loss of response is defined as:

i. Active disease or relapse in spite of thiopurines or methotrexate given at an
appropriate dose for at least 3 months (i.e. azathioprine 2-2.5 mg/kg/day or
mercaptopurine 1-1.5 mg/kg/day in the absence of leukopenia), and/or ii. Active
disease despite corticosteroids treatment (prednisolone up to 0.75 mg/kg/day) over a
period of 4 Weeks, and/or iii. Active disease or relapse in spite of adequate
treatment (as defined in the SmPC) with tumor necrosis factor [TNF] inhibitors or
vedolizumab, and/or iv. Active disease or relapse in spite of adequate treatment with
JAK inhibitors over a period of at least 6 Weeks.

- Patients 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 (=9 mg/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;

- Patients previously treated with tube feeding, defined formula diets, or parenteral
alimentation/nutrition must have discontinued treatment 3 Weeks before the screening
visit and must be able to take, orally, appropriate amount of food (calories) and
liquids to maintain body weight;

- Patients with surveillance colonoscopy defined as per ECCO guidelines;

- Patients with the following hematological and biochemical laboratory parameters
obtained at screening:

i. Hemoglobin > 9.0 g dL-1; ii. Absolute neutrophil count = 750 mm-3; iii. Platelets =
100,000 mm-3; iv. Total serum creatinine = 1.3 x ULN (upper limit of normal); v.
Creatinine clearance > 90 mL min-1 by the Cockcroft-Gault equation within 60 days
prior to baseline; vi. Total serum bilirubin < 1.5 x ULN; vii. Alkaline phosphatase,
AST (SGOT) and ALT (SGPT) < 2 x ULN;

- Patients are 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 are performed;

- Patients should be affiliated to a social security regimen (for French sites only);

- Females and males receiving the study treatment (potentially in combination with
immunosuppressant) and their partners must agree to use a highly effective
contraceptive method during the study and for 6 months after end of study or early
termination. Contraception should be in place at least 2 Weeks prior to study
participation. Women must be surgically sterile or if of childbearing potential must
use a highly effective contraceptive method. Women of childbearing potential (WOCBP)
will enter the study after confirmed menstrual period and a negative pregnancy test.
Highly effective methods of contraception include true abstinence, intrauterine device
(IUD) or hormonal contraception aiming at inhibition of ovulation, intrauterine
hormone releasing system, bilateral tubal ligation, vasectomized partner. True
abstinence is defined when this is in line with the preferred and usual lifestyle of
the patient. In each case of delayed menstrual period (over one month between
menstruations) confirmation of absence of pregnancy is required. This recommendation
also applies to WOCBP with an infrequent or irregular menstrual cycle. Female and male
patients must not be planning pregnancy during the trial and for 6 months post
completion of their participation in the trial. In addition, male participants should
use condoms and not donate sperm as long as contraception is required.

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


Age minimum: 18 Years
Age maximum: 75 Years
Gender: All

Health Condition(s) or Problem(s) studied

Ulcerative Colitis

Intervention(s)

Drug: ABX464 50mg

Drug: ABX464 100mg

Drug: ABX464 25mg

Drug: Placebo

Primary Outcome(s)

Modified Mayo Score [Time Frame: Week 8]

Secondary Outcome(s)

Incidence of adverse events leading to investigational medicinal product discontinuation [Time Frame: Every visit]

Partial Modified Mayo Score [Time Frame: Every visit]

C Reactive Protein [Time Frame: Week 8 and Week 16]

miR-124 expression [Time Frame: Week 8 and Week 16]

Clinical remission [Time Frame: Week 8 and Week 16]

Modified Mayo Score [Time Frame: Week 16]

Fecal calprotectin [Time Frame: Week 8 and Week 16]

Mucosal healing [Time Frame: Week 8 and Week 16]

Stool and rectal bleeding frequency [Time Frame: Every visit]

ABX464 and ABX464-N-Glu [Time Frame: Every visit (Except D57)]

Endoscopy Remission [Time Frame: Week 8 and Week 16]

Clinical response [Time Frame: Week 8 and Week 16]

Endoscopic Improvement [Time Frame: Week 8 and Week 16]

IBDQ [Time Frame: Week 8 and Week 16]

Incidence of treatment-emergent serious adverse event [Time Frame: Every visit]

IL-6, TNFa, IL-1b, IL-10 plasma concentrations [Time Frame: Every visit]

Number and rate of all adverse events, causally-related adverse events, SAE and causally-related SAEs classified by severity [Time Frame: Every visit]

Inflammatory Infiltrate [Time Frame: Week 8 and Week 16]

Number of clinically-significant laboratory abnormalities [Time Frame: Every visit]

Secondary ID(s)

ABX464-103

Source(s) of Monetary Support

Please refer to primary and secondary sponsors