Investigate the efficacy and safety of study drug ABX464 50 mg once daily versus placebo with patients with moderate to severe Active Ulcerative Colitis.

• Register: EUCTR
• Last refreshed on: 28 March 2022
• Main ID: EUCTR2017-000937-30-BE
• Date of registration: 03/08/2017
• Prospective Registration: Yes
• Primary sponsor: ABIVAX
• Public title: Investigate the efficacy and safety of study drug ABX464 50 mg once daily versus placebo with patients with moderate to severe Active Ulcerative Colitis.
• Scientific title: A Phase IIa study to evaluate the safety and efficacy of ABX464 50 mg once daily versus Placebo in subjects with Moderate to Severe Active Ulcerative Colitis who have failed or are intolerant to immunomodulators, Anti-TNFa, vedolizumab and/or corticosteroids. - Safety and efficacy study of ABX464 in patients with moderate to severe Active Ulcerative Colitis.
• Date of first enrolment: 29/09/2017
• Target sample size: 30
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-000937-30
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Belgium, France, Germany, Hungary, Poland, Spain

Contacts

• Name: Head of Clinical Operations
• Affiliation: Abivax

• Name: Head of Clinical Operations
• Affiliation: Abivax

Key inclusion & exclusion criteria

Inclusion criteria:
-Men or women age 18 - 75 years;

- 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 Mayo Clinic Score (MCS) of 6 to 12 inclusive (on a scale of 0-12). Moderate to severe active UC should be confirmed at screening visit with a centrally read MCS endoscopy score of at least 2 (on a scale of 0-3);

-Subjects 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 (=9mg/day), for =2 weeks before the screening visit;

-Topical corticosteroids and topical 5-aminosalicylic acid preparations must have been withdrawn =2 weeks before the screening visit due to inefficacy or intolerance.
-Subjects who are on oral 5-aminosalicylic acid must have been on a stable dose =4 weeks before the screening visit;

-Subjects who are receiving immunosuppressants in the form of azathioprine, 6-mercaptopurine, or methotrexate needed to be on a stable dose for 4 weeks before the screening visit. Subjects taking methotrexate also are advised to take folic acid 1 mg/day (or equivalent) supplementation if there is no contraindication;

-Subjects on probiotics (e.g., Culturelle® [Lactobacillus GG, i-Health, Inc.], Saccharomyces boulardii) must be on stable doses for 2 weeks before the screening visit;

-Subjects on antidiarrheals (e.g., loperamide, diphenoxylate with atropine) must be on stable doses for 2 weeks before the screening visit;

-Subjects who have previously received anti-tumor necrosis factor (TNF) therapy or vedolizumab must have discontinued therapy =8 weeks before the screening visit due to inefficacy or intolerance.

-Subjects previously treated with cyclosporine or tacrolimus must have discontinued therapy =4 weeks before the screening visit due to inefficacy or intolerance.
-Subjects previously treated with tube feeding, defined formula diets, or parenteral alimentation/nutrition must have discontinued treatment 3 weeks before the screening visit;

-Subjects with hematological and biochemical laboratory parameters as follows and within 14 days of baseline:
o Hemoglobin > 9.0 g dL-1;
o Absolute neutrophil count = 750 mm-3;
o Platelets = 100,000 mm-3;
o Total serum creatinine = 1.3 x ULN (upper limit of normal);
o Creatinine clearance > 50 mL min-1 by the
Cockcroft-Gault equation within 60 days of entry;
o Total serum bilirubin < 1.5 x ULN;
o Alkaline phosphatase, AST (SGOT) and ALT (SGPT) < 1.5 x
ULN;

-Subjects should be able and willing to comply with study visits and procedures as per protocol;

-Subjects should understand, sign and date the written voluntary informed consent form at the screening visit prior to any protocol-specific procedures being performed;

-Subjects 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. 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
Exclusion criteria:
-Subject with Crohn's Disease (CD), indeterminate colitis (IC) or presence or history of fistula with CD;

-History of toxic megacolon, abdominal abscess, symptomatic colonic stricture or stoma; history or is at imminent risk of colectomy;

-History or current evidence of colonic dysplasia or adenomatous colonic polyps. Subject with severe gastrointestinal complications; e.g., short bowel syndromes, obstructing strictures, recent or planned bowel surgery, Ileostomy and/or colostomy, recent bowel perforation;
-Subject with significant and known active infections at screening such as Infected abscess, positive for Clostridium difficile (stool antigen and toxin), CMV, TB and recent infectious hospitalization;

- Acute, chronic or history of clinically relevant pulmonary, cardiovascular, hepatic, pancreatic or renal functional abnormality, encephalopathy, neuropathy or unstable CNS pathology, 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 unless there has been surgical excision that is considered to have achieved cure;

- Active malignancy that may require chemotherapy or radiation therapy;

- Seizure disorder or any history of prior seizure;

- Serious illness requiring systemic treatment and/or hospitalization within 3 weeks prior to baseline;

- Pregnant or breast-feeding woman;

- Active 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 subject's safety or adherence to the study protocol.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Moderate to severe Ulcerative Colitis.
MedDRA version: 20.1 Level: LLT Classification code 10066678 Term: Acute ulcerative colitis System Organ Class: 100000004856

Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Intervention(s)

Product Code: ABX464
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: ABX464
Current Sponsor code: ABX464
Other descriptive name: ABX464
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: To evaluate the effect of ABX464 :
-on the expression of IL-22 in serum and rectal/sigmoidal tissue compared to placebo in subjects with Moderate to Severe Active Ulcerative Colitis.
-on miR-124 expression in whole blood (PAXgene®) and in tissue (RNA later) vs placebo in subjects with Moderate to Severe Active Ulcerative Colitis.
-on the rectal/sigmoidal infiltrates (Geboes score) vs placebo in subjects with Moderate to Severe Active Ulcerative Colitis.
-on the rectal microbiome compared to placebo in subjects with Moderate to Severe Active Ulcerative Colitis
-on endoscopic remission vs placebo in subjects with Moderate to Severe Active Ulcerative Colitis.
-on clinical remission and response vs placebo in subjects with Moderate to Severe Active Ulcerative Colitis.
-on Quality of Life (QoL) measured by the SF-36 questionnaire vs placebo in subjects with Moderate to Severe Active Ulcerative Colitis.
- to assess pharmacokinetic parameters in subjects.

Main Objective: The primary objective of the study is to evaluate safety of ABX464 given at 50 mg once daily versus Placebo in subjects with Moderate to Severe Active Ulcerative Colitis who have failed or are intolerant to immunomodulators, Anti-TNFa, vedolizumab and/or corticosteroids.

Timepoint(s) of evaluation of this end point: Timepoint of evaluation of this end point from day 0 to EoS.

Primary end point(s): Number of incidences of treatment-emergent adverse events in the ABX464 treated subjects compared to placebo.

Secondary Outcome(s)

Secondary end point(s): Secondary Endpoints:
Primary Efficacy endpoint:
1.The proportion of subjects receiving ABX464 with clinical remission according to the Total Mayo Score at week 8 compared to placebo.Remission exclude friability and is based on total Mayo score = 2 with no
individual sub-score > 1.

Other secondary endpoints:

2.The change from screening in IL-22 expression levels in serum and rectal/sigmoidal tissue at week 8 compared to placebo.
3.The change from baseline in microRNA-124 levels in whole blood (PAXgene®) and in tissue (RNA later) at week 4 and week 8 compared to placebo.
4.The change from baseline in fecal calprotectin levels at week 4 and week 8 compared to placebo.
5.The change from screening in the histopathology/infiltrate (rectal/sigmoidal biopsies) assessed by the Geboes score at week 8 compared to placebo.
6.The change from screening in rectal microbiota using taxonomic markers at week 8 compared to placebo
7.The change from screening in Total Mayo Score in subjects receiving ABX464 at week 8 compared to placebo.
8.The change from baseline in Partial Mayo Score in subjects receiving ABX464 at week 4 and week 8 compared to placebo.
9.The proportion of subjects achieving endoscopic remission at week 8. Endoscopic remission is defined as a Mayo endoscopic sub-score of 0.
10.The proportion of subjects achieving improvement in endoscopic appearance at week 8. Improvement of endoscopic appearance is defined as a Mayo endoscopic sub-score of = 1.
11.The proportion of subjects achieving a symptomatic remission at week 8. Symptomatic remission is defined as a total Mayo Score = 2 with no individual sub-score > 1 and rectal bleeding and stool frequency sub-scores of 0.
12.The time to UC worsening after week 8.
13.The serum concentration evaluation of ABX464 and its metabolites levels.
14.The scores and changes from baseline in SF-36 Questionnaire scores at week 4 and week 8.
15.The number of incidences of treatment-emergent serious adverse events.
16.The number of incidences of treatment-emergent adverse events of special interest.
17.The number of incidences of adverse events leading to investigational product discontinuation.
18.The number of incidences of specific laboratory abnormalities.

Timepoint(s) of evaluation of this end point: 1. At week 8 compared to placebo.
2. At week 4 and week 8 compared to placebo.
3. At week 4 and week 8 compared to placebo.
4. At week 8 compared to placebo.
5. At week 8 compared to placebo.
6. At week 8 compared to placebo.
7.At week 4 and week 8 compared to placebo.
8.At week 8 compared to placebo.
9.At week 8.
10. At week 8.
11. At week 8.
12. After week 8.
13. As per metabolite levels.
14. At week 4 and week 8.
15. Throughout the study.
16. Throughout the study.
17. Throughout the study.
18. Throughout the study.

Secondary ID(s)

ABX464-101

Source(s) of Monetary Support

Abivax

Ethics review

Status: Approved
Approval date: 29/09/2017
Contact:

Results

• Results available: Yes
• Date Posted: 28/10/2021
• Date Completed: 04/02/2019
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2017-000937-30/results