Efficacy and Safety of Orally Administered BBT-401-1S in Subjects With Ulcerative Colitis

Study Overview
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Brief Summary
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This is a randomised, double-blind, placebo-controlled, proof of clinical principle study to explore the efficacy and safety of orally administered BBT-401-1S in subjects with ulcerative colitis.

Official Title
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A Randomised, Double-blind, Placebo-controlled Study of Orally Administered BBT-401-1S in Subjects With Moderate to Severe Ulcerative Colitis, Incorporating a Response-adaptive, Double-blind Extension Phase

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Drug: BBT-401-1S or Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, of any race, ≥18 and ≤60 years of age. Have been diagnosed with active UC for ≥3 months prior to Day 1, as determined by clinical and endoscopic evidence and documented in a histopathology evaluation. Have a total Mayo score ≥6, an endoscopic subscore ≥2, rectal bleeding subscore ≥1, and a stool frequency subscore ≥1, regardless of standard of care history. Able to comprehend and willing to voluntarily sign an ICF and to abide by the study restrictions. Exclusion Criteria: Have received: intravenous corticosteroids, rectally administered corticosteroids, or rectally administered 5-aminosalicylic acid within 3 weeks, or Janus kinase (JAK) inhibitors within 2 weeks, or cyclosporine, mycophenolate, tacrolimus, or methotrexate within 5 weeks, or anti-TNF-α biologics within 9 weeks, or any other biologics (including ustekinumab and vedolizumab) for the treatment of UC within 12 weeks. Have received orally administered azathioprine or 6-mercaptopurine that has been stable for <8 weeks. Have received orally administered 5-aminosalicylic acid, sulphasalazine, or low-dose corticosteroids (prednisolone ≤20 mg/day or equivalent) that have been stable for <5 weeks. Have received any other concomitant medications for UC that have been stable (ie, have not started dosing with a new drug or had a change to their dosing regimen) for <7 days or 5 half-lives, whichever is longer. Have Crohn's disease, indeterminate colitis, ischaemic colitis, fulminant colitis, toxic megacolon, chronic (as determined by the investigator) pancolitis, confined proctitis (distal, ≤15 cm), or symptomatic intestinal stenosis. Have a history of extensive colonic resection (subtotal or total colectomy) or are anticipated to require surgical intervention for UC. Have an ileostomy, colostomy, or known fixed symptomatic stenosis of the intestine. Have a positive test for Clostridium difficile, or have evidence of treatment for Clostridium difficile infection or other pathogenic bowel infection within 60 days or for another intestinal pathogen within 30 days prior to Day 1.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BBT-401-1S (800mg)<br>Induction Phase: BBT-401 800mg for 8 weeks Extension Phase: After 8 weeks, Participants who achieved clinical remission in the induction phase will continue the same treatment for 8 weeks Participants who did not achieve clinical remission in the induction phase will receive BBT-401 1600mg for 8 weeks | Drug: BBT-401-1S or Placebo<br>* Administered by 200mg capsules of BBT-401-1S or placebo<br>|
| Experimental: BBT-401-1S (1,600mg)<br>Induction Phase: BBT-401 1600mg for 8 weeks Extension Phase: After 8 weeks, Participants will continue the same treatment for 8 weeks | Drug: BBT-401-1S or Placebo<br>* Administered by 200mg capsules of BBT-401-1S or placebo<br>|
| Placebo Comparator: Placebo<br>Induction Phase: Placebo for 8 weeks Extension Phase: After 8 weeks, Participants who achieved clinical remission in the induction phase will continue the same treatment for 8 weeks Participants who did not achieve clinical remission in the induction phase will receive BBT-401 800mg for 8 weeks | Drug: BBT-401-1S or Placebo<br>* Administered by 200mg capsules of BBT-401-1S or placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Achieved a Clinical Response by Total Mayo Score at Day 57 | Clinical Response was defined as a Total Mayo Score, as measured by a reduction of ≥ 3 points and ≥ 30% improvement from baseline of Total Mayo Score, which included a decrease in rectal bleeding subscore of ≥ 1 point or an absolute rectal bleeding subscore ≤ 1 | Day 57 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Achieved a Clinical Remission by Total Mayo Score at Day 57 | Clinical Remission was defined as a Total Mayo score, as measured by a total Mayo score of ≤ 2 points, with no individual subscore exceeding 1 point. Change from baseline to Day 57 in Total Mayo Score. The Total Mayo Score is consisted of 4 subscores (stool frequency, rectal bleeding, findings on endoscopy, physician's global assessment), each graded from 0 to 3 with higher scores indicating more severe disease | Day 57 | 
| Percentage of Participants Who Achieved an Endoscopic Remission at Day 57 | Endoscopic Remission was defined as a Mayo endoscopic subscore of 0 or 1. Change from baseline to Day 57 in Total Mayo Score. The Total Mayo Score is consisted of 4 subscores (stool frequency, rectal bleeding, findings on endoscopy, physician's global assessment), each graded from 0 to 3 with higher scores indicating more severe disease | Day 57 | 
| Change From Baseline to Day 57 in Total Mayo Score | Change from Baseline to Day 57 in Total Mayo Score. Change from baseline to Day 57 in Total Mayo Score. The Total Mayo Score, ranged from 0 to 12, are sum of 4 subscores. Subscores are stool frequency, rectal bleeding, findings on endoscopy, and physician's global assessment, each graded from 0 to 3 with higher scores indicating more severe disease. | Baseline, Day 57 |