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

Phase 2

Terminated

Conditions: Ulcerative Colitis

Interventions: Drug: BBT-401-1S first and then Placebo
Drug: Placebo first and then BBT-401-1S

Registration Number: NCT03800420

Lead Sponsor: Bridge Biotherapeutics, Inc.

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 16

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
BBT-401-1S	BBT-401-1S first and then Placebo	BBT-401-1S, Oral capsule, QD
Placebo	Placebo first and then BBT-401-1S	Placebo, Oral capsule, QD

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Total Mayo Score	Week 8	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.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Partial Mayo Score	Week 8	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.
Change From Baseline in Histologic Assessment of Endoscopic Biopsy	Week 8	Histological assessment of endoscopic biopsy is an appropriate method for evaluating mucosal healing (Carbonnel et al, 1994).
Change From Baseline in Ulcerative Colitis Endoscopic Index of Severity (0-8)	Week 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.
Number and Severity of TEAEs	up to 8 weeks after the last dose	Treatment Emergent Adverse Event (TEAE) is defined as an adverse event that occurs or worsens on or after the first dose of study drug.
Plasma Concentration of BBT- 401-1S	Day 1, Week 4, Week 8	Analysis of Plasma Pharmacokinetics for BBT- 401 -1S
Change From Baseline in Concentration of Serum CRP	Week 8	Widely used serum indicator of inflammation in Ulcerative Colitis(UC).
Change From Baseline in Concentration of Fecal Calprotectin	Week 8	Reliable surrogate marker for disease activity in Ulcerative Colitis (UC).
Change From Baseline in Concentration of Fecal Lactoferrin	Week 8	A stool (fecal) test that is used to detect inflammation in the intestines.

Trial Locations

Locations (11): Site 13
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McAllen, Texas, United States
Site 11
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Boca Raton, Florida, United States
Site 12
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Pembroke Pines, Florida, United States
Site 09
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Seattle, Washington, United States
Site 01
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Ventura, California, United States
Site 04
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Rockville, Maryland, United States
Site 02
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Monroe, North Carolina, United States
Site 08
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Chattanooga, Tennessee, United States
Site 03
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Sacramento, California, United States
Site 10
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Ann Arbor, Michigan, United States
Site 05
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Austin, Texas, United States