Ulcerative Colitis
Conditions
Brief summary
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.
Interventions
DRUGBBT-401-1S or Placebo
Administered by 200mg capsules of BBT-401-1S or placebo
Sponsors
Covance
Bridge Biotherapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
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: 1. intravenous corticosteroids, rectally administered corticosteroids, or rectally administered 5-aminosalicylic acid within 3 weeks, or 2. Janus kinase (JAK) inhibitors within 2 weeks, or 3. cyclosporine, mycophenolate, tacrolimus, or methotrexate within 5 weeks, or 4. anti-TNF-α biologics within 9 weeks, or 5. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved a Clinical Response by Total Mayo Score at Day 57 | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved a Clinical Remission by Total Mayo Score at Day 57 | 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 |
| Percentage of Participants Who Achieved an Endoscopic Remission at Day 57 | 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 |
| Change From Baseline to Day 57 in Total Mayo Score | Baseline, Day 57 | 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. |
Countries
Poland, South Korea, Ukraine, United States
Participant flow
Pre-assignment details
Participants with moderate to severe Ulcerative Colitis (UC) were to be randomly assigned in a 1:1:1 ratio to 1 of 3 treatment groups. A total of 38 participants were enrolled and evaluated as Safety Population. Out of 38 participants, and 33 were considered Intent-to-Treatment Population and evaluated for study outcomes.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo for 8 weeks as induction phase + Placebo or BBT-401-1S 800mg for 8 weeks as extension phase | 11 |
| BBT-401-1S (800mg) BBT-401-1S 800mg for 8 weeks as induction phase + BBT-401-1S 800mg or BBT-401-1S 1600mg for 8 weeks as extension phase | 11 |
| BBT-401-1S (1,600mg) BBT-401-1S 1600mg for 8 weeks as induction phase + BBT-401-1S 1600mg for 8 weeks as extension phase | 11 |
| Total | 33 |
Baseline characteristics
| Characteristic | BBT-401-1S (800mg) | BBT-401-1S (1,600mg) | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 35.0 years STANDARD_DEVIATION 9.9 | 42.1 years STANDARD_DEVIATION 9.1 | 47.0 years STANDARD_DEVIATION 9.6 | 41.4 years STANDARD_DEVIATION 10.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 10 Participants | 11 Participants | 32 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 10 Participants | 10 Participants | 11 Participants | 31 Participants |
| Region of Enrollment Poland | 4 Participants | 1 Participants | 0 Participants | 5 Participants |
| Region of Enrollment South Korea | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Region of Enrollment Ukraine | 6 Participants | 8 Participants | 11 Participants | 25 Participants |
| Region of Enrollment United States | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Female | 4 Participants | 5 Participants | 4 Participants | 13 Participants |
| Sex: Female, Male Male | 7 Participants | 6 Participants | 7 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 12 | 0 / 13 | 0 / 6 | 0 / 8 | 0 / 17 |
| other Total, other adverse events | 1 / 13 | 3 / 12 | 1 / 13 | 1 / 6 | 2 / 8 | 4 / 17 |
| serious Total, serious adverse events | 0 / 13 | 1 / 12 | 0 / 13 | 0 / 6 | 0 / 8 | 0 / 17 |
Outcome results
Primary
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
Time frame: Day 57
Population: The intent-to-treat (ITT) population included all subjects who receive at least 1 dose of study drug, and who have a partial Mayo score recorded on Day 1 and at least 1 post-baseline Mayo score recorded. Subjects are categorized in the treatment group to which they are randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Achieved a Clinical Response by Total Mayo Score at Day 57 | 63.6 Percentage of participants |
| BBT-401-1S (800mg) | Percentage of Participants Who Achieved a Clinical Response by Total Mayo Score at Day 57 | 54.5 Percentage of participants |
| BBT-401-1S (1,600mg) | Percentage of Participants Who Achieved a Clinical Response by Total Mayo Score at Day 57 | 54.5 Percentage of participants |
p-value: 1Fisher Exact
p-value: 1Fisher Exact
Secondary
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.
Time frame: Baseline, Day 57
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline to Day 57 in Total Mayo Score | Day 57 | 4.5 Scores on a scale | Standard Deviation 3.17 |
| Placebo | Change From Baseline to Day 57 in Total Mayo Score | Baseline | 8.8 Scores on a scale | Standard Deviation 1.08 |
| Placebo | Change From Baseline to Day 57 in Total Mayo Score | Change from Baseline | -4.3 Scores on a scale | Standard Deviation 2.72 |
| BBT-401-1S (800mg) | Change From Baseline to Day 57 in Total Mayo Score | Day 57 | 6.2 Scores on a scale | Standard Deviation 3.37 |
| BBT-401-1S (800mg) | Change From Baseline to Day 57 in Total Mayo Score | Change from Baseline | -2.9 Scores on a scale | Standard Deviation 2.47 |
| BBT-401-1S (800mg) | Change From Baseline to Day 57 in Total Mayo Score | Baseline | 9.1 Scores on a scale | Standard Deviation 1.7 |
| BBT-401-1S (1,600mg) | Change From Baseline to Day 57 in Total Mayo Score | Change from Baseline | -2.6 Scores on a scale | Standard Deviation 1.71 |
| BBT-401-1S (1,600mg) | Change From Baseline to Day 57 in Total Mayo Score | Baseline | 8.4 Scores on a scale | Standard Deviation 1.75 |
| BBT-401-1S (1,600mg) | Change From Baseline to Day 57 in Total Mayo Score | Day 57 | 5.6 Scores on a scale | Standard Deviation 2.55 |
p-value: 0.5808ANCOVA
p-value: 0.2143ANCOVA
Secondary
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
Time frame: Day 57
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Achieved a Clinical Remission by Total Mayo Score at Day 57 | 36.4 Percentage of Participants |
| BBT-401-1S (800mg) | Percentage of Participants Who Achieved a Clinical Remission by Total Mayo Score at Day 57 | 18.2 Percentage of Participants |
| BBT-401-1S (1,600mg) | Percentage of Participants Who Achieved a Clinical Remission by Total Mayo Score at Day 57 | 9.1 Percentage of Participants |
p-value: 0.6351Fisher Exact
p-value: 0.3108Fisher Exact
Secondary
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
Time frame: Day 57
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Achieved an Endoscopic Remission at Day 57 | 45.5 Percentage of Participants |
| BBT-401-1S (800mg) | Percentage of Participants Who Achieved an Endoscopic Remission at Day 57 | 36.4 Percentage of Participants |
| BBT-401-1S (1,600mg) | Percentage of Participants Who Achieved an Endoscopic Remission at Day 57 | 27.3 Percentage of Participants |
p-value: 1Fisher Exact
p-value: 0.6594Fisher Exact