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

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

Status

Terminated

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03800420

Enrollment

Registered

2019-01-11

Start date

2019-04-22

Completion date

2020-07-31

Last updated

2022-03-21

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Ulcerative Colitis

Keywords

Pellino-1

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.

Interventions

DRUGBBT-401-1S first and then Placebo

Total 16 week treatment period: The subject takes BBT-401-1S, QD for the first 12 weeks, then placebo for the last 4 weeks.

DRUGPlacebo first and then BBT-401-1S

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.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
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.
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 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.
Plasma Concentration of BBT- 401-1S	Day 1, Week 4, Week 8	Analysis of Plasma Pharmacokinetics for BBT- 401 -1S

Countries

United States

Participant flow

Participants by arm

Arm	Count
BBT-401-1S BBT-401-1S, Oral capsule, QD BBT-401-1S first and then Placebo: Total 16 week treatment period: Subject takes BBT-401-1S and Placebo. If the subject takes BBT-401-1S, QD for the first 12 weeks, then placebo for the last 4 weeks.	12
Placebo Placebo, Oral capsule, QD Placebo first and then BBT-401-1S: Total 16 week treatment period: Subject take BBT-401-1S and Placebo. If the subject takes the placebo, QD for the first 8 weeks, then BBT-401-1S for the last 8 weeks.	4
Total	16

Baseline characteristics

Characteristic	BBT-401-1S	Placebo	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	1 Participants	0 Participants	1 Participants
Age, Categorical Between 18 and 65 years	11 Participants	4 Participants	15 Participants
Race/Ethnicity, Customized Race Mixed (White/Black)	1 Participants	0 Participants	1 Participants
Race/Ethnicity, Customized Race White	11 Participants	4 Participants	15 Participants
Sex: Female, Male Female	4 Participants	1 Participants	5 Participants
Sex: Female, Male Male	8 Participants	3 Participants	11 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 12	0 / 4
other Total, other adverse events	8 / 12	1 / 4
serious Total, serious adverse events	0 / 12	0 / 4

Outcome results

Primary

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.

Time frame: Week 8