Ulcerative Colitis
Conditions
Keywords
ABX464, Ulcerative Colitis, Refractory
Brief summary
This Phase IIa study is an 8-week, double-blind, placebo-controlled, randomized study aiming at evaluating the safety and the efficacy of ABX464 given once a day (o.d) at 50 mg in subjects with moderate to severe Active Ulcerative Colitis who have failed or are intolerant to immunomodulators, Anti-TNFα, vedolizumab and/or corticosteroids followed by a one-month follow-up period.
Detailed description
This Phase IIa study is an 8-week, double-blind, placebo-controlled, randomized study aiming at evaluating the safety and the efficacy of ABX464 given once a day (o.d) at 50 mg in subjects with moderate to severe Active Ulcerative Colitis who have failed or are intolerant to immunomodulators, Anti-TNFα, vedolizumab and/or corticosteroids followed by a one-month follow-up period. Eligible subjects will be randomized according to a 2/1 ratio in two different groups of treatment. Randomized subjects who will receive 50 mg ABX464 orally once daily for 56 days.
Interventions
DRUGABX464
ABX464 is a new Anti-inflammatory drug
DRUGPlacebo oral capsule
Placebo matching with ABX464
Sponsors
Abivax S.A.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double-Blind Treatment
Intervention model description
Double-blind, placebo-controlled, randomized study
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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 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 first dosing (i.e. baseline); * Topical corticosteroids and topical 5-aminosalicylic acid preparations must have been withdrawn ≥2 weeks before first dosing (i.e. baseline); * Subjects who are on oral 5-aminosalicylic acid must have been on a stable dose ≥4 weeks before first dosing (i.e. baseline); * 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 first dosing (i.e. baseline). 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 first dosing (i.e. baseline); * Subjects on antidiarrheals (e.g., loperamide, diphenoxylate with atropine) must be on stable doses for 2 weeks before first dosing (i.e. baseline); * Subjects who have previously received anti-tumor necrosis factor (TNF) therapy or vedolizumab must have discontinued therapy ≥8 weeks before first dosing (i.e. baseline); * Subjects previously treated with cyclosporine or tacrolimus must have discontinued therapy ≥4 weeks before first dosing (i.e. baseline); * Subjects previously treated with tube feeding, defined formula diets, or parenteral alimentation/nutrition must have discontinued treatment 3 weeks before first dosing (i.e. baseline).
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;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Treatment-emergent Adverse Events | Week 8 | Number of treatment-emergent adverse events in the ABX464 treated subjects compared to placebo |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Remission | Week 8 | Percentage of subjects receiving ABX464 with clinical remission according to the Total Mayo Score at Week 8 compared to placebo (primary efficacy endpoint) |
| Fecal Calprotectin | Week 8 | Percentage of patients with fecal calprotectin levels \> 50µg/g at Week 8 compared to placebo |
| Total Mayo Score | Week 8 | Change from baseline in Total Mayo Score in subjects receiving ABX464 compared to placebo. The scale ranges from 0 to 12; 12 being the worst score) - 4-component Scale: Rectal bleeding, Stool frequency, Mucosal appearance and Physician Global Assessment |
| Change in Partial Mayo Score | Week 8 | Change from baseline in Partial Mayo Score in subjects receiving ABX464 compared to placebo. The scale ranges from 0 to 9, with 9 indicating the worst score. It is a three-component scale assessing rectal bleeding, stool frequency, and the physician's global assessment. |
Countries
Austria, Belgium, Czechia, France, Germany, Hungary, Poland, Spain
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ABX464 Treatment Arm Subjects will receive 50 mg of ABX464 orally once daily for 56 days.
ABX464: ABX464 is a new Anti-inflammatory drug | 23 |
| ABX464 Matching Placebo Treatment Arm Subjects will receive 50 mg of ABX464 matching Placebo orally once daily for 56 days.
Placebo oral capsule: Placebo matching with ABX464 | 9 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | ABX464 Treatment Arm | ABX464 Matching Placebo Treatment Arm | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 0 Participants | 4 Participants |
| Age, Categorical Between 18 and 65 years | 19 Participants | 9 Participants | 28 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 23 Participants | 9 Participants | 32 Participants |
| Sex: Female, Male Female | 11 Participants | 1 Participants | 12 Participants |
| Sex: Female, Male Male | 12 Participants | 8 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 23 | 0 / 9 |
| other Total, other adverse events | 18 / 23 | 5 / 9 |
| serious Total, serious adverse events | 0 / 23 | 1 / 9 |
Outcome results
Primary
Number of Subjects With Treatment-emergent Adverse Events
Number of treatment-emergent adverse events in the ABX464 treated subjects compared to placebo
Time frame: Week 8
Population: All subjects who received at least 1 dose of study treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ABX464 Treatment Arm | Number of Subjects With Treatment-emergent Adverse Events | 18 Participants |
| ABX464 Matching Placebo Treatment Arm | Number of Subjects With Treatment-emergent Adverse Events | 5 Participants |
p-value: 0.2096Chi-squared
Secondary
Change in Partial Mayo Score
Change from baseline in Partial Mayo Score in subjects receiving ABX464 compared to placebo. The scale ranges from 0 to 9, with 9 indicating the worst score. It is a three-component scale assessing rectal bleeding, stool frequency, and the physician's global assessment.
Time frame: Week 8
Population: Subjects in the FAS without any major protocol deviations and who completed the study (Day 56)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ABX464 Treatment Arm | Change in Partial Mayo Score | -3.9 units on a scale | Standard Deviation 2.2 |
| ABX464 Matching Placebo Treatment Arm | Change in Partial Mayo Score | -1.8 units on a scale | Standard Deviation 2 |
p-value: 0.0462ANCOVA
Secondary
Clinical Remission
Percentage of subjects receiving ABX464 with clinical remission according to the Total Mayo Score at Week 8 compared to placebo (primary efficacy endpoint)
Time frame: Week 8
Population: Subjects in the FAS without any major protocol deviations and who completed the study (Day 56)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ABX464 Treatment Arm | Clinical Remission | 7 Participants |
| ABX464 Matching Placebo Treatment Arm | Clinical Remission | 1 Participants |
p-value: 0.1588Chi-squared
Secondary
Fecal Calprotectin
Percentage of patients with fecal calprotectin levels \> 50µg/g at Week 8 compared to placebo
Time frame: Week 8
Population: Subjects in the FAS without any major protocol deviations and who completed the study (Day 56)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ABX464 Treatment Arm | Fecal Calprotectin | 15 Participants |
| ABX464 Matching Placebo Treatment Arm | Fecal Calprotectin | 8 Participants |
p-value: 0.483ANCOVA
Secondary
Total Mayo Score
Change from baseline in Total Mayo Score in subjects receiving ABX464 compared to placebo. The scale ranges from 0 to 12; 12 being the worst score) - 4-component Scale: Rectal bleeding, Stool frequency, Mucosal appearance and Physician Global Assessment
Time frame: Week 8
Population: Subjects in the FAS without any major protocol deviations and who completed the study (Day 56)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ABX464 Treatment Arm | Total Mayo Score | -4.6 score on a scale | Standard Deviation 2.8 |
| ABX464 Matching Placebo Treatment Arm | Total Mayo Score | -2.1 score on a scale | Standard Deviation 2.5 |
p-value: 0.0742ANCOVA