Efficacy and Safety of BBT-401-1S in Ulcerative Colitis

Study Overview
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Brief Summary
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This is randomized, placebo-controlled, dose-escalation, multicenter, Phase 2 study to evaluate the efficacy and safety of BBT-401-1S in patients with active ulcerative colitis. This study consists of three cohorts with 16-week treatment period per cohort that will be conducted sequentially.

Official Title
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A Multicenter, Randomized, Double-blind, Placebo-controlled, Phase 2a Study to Evaluate the Efficacy and Safety of BBT-401-1S in Patients With Active Ulcerative Colitis

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Drug: BBT-401-1S first and then Placebo
* Drug: Placebo first and then BBT-401-1S


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of signed and dated informed consent form (ICF) Stated willingness to comply with all study procedures and availability for the duration of the study Male or female, aged >=18 years Diagnosed with active UC for at least 3 months prior to screening Total Mayo score >=5 and Endoscopic sub-score >=1 Stable dosing regimens of oral drugs (if currently administered) as follows: 5-ASA or sulfasalazine at a stable dose for at least 4 weeks, purine analogues (azathioprine, mercaptopurine, thiopurines) or methotrexate at a stable dose for at least 12 weeks, and low-dose oral corticosteroid (up to 20 mg prednisone/day or equivalent) for at least 4 weeks prior to the first dose of study treatment. Doses of oral drugs must remain stable until the end of study treatment (with possible exception for tapering steroid dose after 8 weeks) For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation and for an additional 3 months after the last dose For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner during study participation and for an additional 3 months after the last dose Exclusion Criteria: Use of anti-TNF-a biologics or any other biologics for treatment of UC within 60 days prior to randomization. Any rectal therapy for treatment of UC or intravenous corticosteroids within 2 weeks prior to randomization. Presence of Crohn's disease, indeterminate colitis, ischemic colitis, fulminant colitis, ulcerative proctitis, or toxic mega-colon Previous extensive colonic resection (subtotal or total colectomy) Ileostomy, colostomy, or known fixed symptomatic stenosis of the intestine Evidence of or treatment for Clostridium difficile infection or other pathogenic bowel infection within 60 days or for another intestinal pathogen within 30 days prior to randomization Active infection with the HIV or Hepatitis B or C viruses Clinically significant active extra-intestinal infection (e.g., pneumonia, pyelonephritis) Clinically significant abnormal vital signs, physical examination or 12-lead electrocardiogram (ECG) at screening or baseline Clinically significant abnormal results of liver function tests (ALT/AST, bilirubin and alkaline phosphatase) > 2X the upper limit of normal (ULN) at screening Other clinically significant abnormal laboratory results at screening in the investigator's opinion History of any clinically significant medical condition that, in the investigator's opinion, would preclude participation in the study Pregnancy or lactation Treatment with another investigational drug or other intervention within 30 days prior to screening

Ages Eligible for Study
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Minimum Age: 18 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BBT-401-1S<br>BBT-401-1S, Oral capsule, QD | Drug: BBT-401-1S first and then Placebo<br>* Total 16 week treatment period: The subject takes BBT-401-1S, QD for the first 12 weeks, then placebo for the last 4 weeks.<br>|
| Placebo Comparator: Placebo<br>Placebo, Oral capsule, QD | Drug: Placebo first and then BBT-401-1S<br>* Total 16 week treatment period: The subject takes the placebo, QD for the first 8 weeks, then BBT-401-1S for the last 8 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Total Mayo Score | The Total Mayo score is an instrument designed to measure disease activity of ulcerative colitis, with scores ranging from 0 to 12 points. The Total Mayo score consists of 4 subscores( Stool frequency, Rectal bleeding, Findings of endoscopy, Physician global assessment), each graded from 0 to 3 with higher scores indicating more severe disease. | Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Partial Mayo Score | The Partial Mayo score is an instrument designed to measure disease activity of ulcerative colitis, with scores ranging from 0 to 9 points. The Partial Mayo score consists of 3 subscores( Stool frequency, Rectal bleeding, Physician global assessment), each graded from 0 to 3 with higher scores indicating more severe disease. | Week 8 | 
| Change From Baseline in Histologic Assessment of Endoscopic Biopsy | Histological assessment of endoscopic biopsy is an appropriate method for evaluating mucosal healing (Carbonnel et al, 1994). | Week 8 | 
| Change From Baseline in Ulcerative Colitis Endoscopic Index of Severity (0-8) | The Ulcerative Colitis Endoscopic Index of Severity (UCEIS) is the first validated index for the assessment of overall endoscopic activity. The model incorporates the vascular pattern score(0-2), the presence of bleeding score(0-3) and the presence of erosions and ulcers score (0-3). Higher score of the sum of these subscore indicates more severe disease. | Week 8 | 
| Number and Severity of TEAEs | Treatment Emergent Adverse Event (TEAE) is defined as an adverse event that occurs or worsens on or after the first dose of study drug. | up to 8 weeks after the last dose | 
| Plasma Concentration of BBT- 401-1S | Analysis of Plasma Pharmacokinetics for BBT- 401 -1S | Day 1, Week 4, Week 8 | 
| Change From Baseline in Concentration of Serum CRP | Widely used serum indicator of inflammation in Ulcerative Colitis(UC). | Week 8 | 
| Change From Baseline in Concentration of Fecal Calprotectin | Reliable surrogate marker for disease activity in Ulcerative Colitis (UC). | Week 8 | 
| Change From Baseline in Concentration of Fecal Lactoferrin | A stool (fecal) test that is used to detect inflammation in the intestines. | Week 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pellino-1