Ulcerative Colitis
Conditions
Brief summary
The purpose of this study is to assess the safety and efficacy of oral deucravacitinib in participants with moderate to severe ulcerative colitis (UC).
Interventions
DRUGBMS-986165
Specified Dose on Specified Days
OTHERPlacebo
Specified Dose on Specified Days
Sponsors
Bristol-Myers Squibb
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 80 Years
Healthy volunteers
No
Inclusion criteria
For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: * Must have active ulcerative colitis (UC) extending ≥ 15 cm from the anal verge and confirmed by a screening/baseline colonoscopy/sigmoidoscopy prior to the randomization visit * Must have documented diagnosis of UC of at least 3 months' duration prior to screening * Must have active moderate to severe UC, as defined by a modified Mayo score of 5 to 9 points, inclusive, which includes a stool frequency (SF) subscore of ≥ 2, and a rectal bleeding (RB) subscore ≥ 1, and a screening endoscopic (ES) subscore of ≥ 2
Exclusion criteria
* Previous/current documented diagnosis of CD, indeterminate colitis, ischemic colitis, or pseudomembranous colitis (other than associated with Clostridium difficile \[C. difficile\]) * Stool positive for C. difficile toxin at screening visit * Current or recent (within 12 weeks prior to the randomization visit) evidence of fulminant colitis, abdominal abscess, toxic megacolon, or bowel perforation Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Remission Response Rate at Week 12 | From first dose to 12 weeks. | Clinical remission response rate is the percentage of participants achieving clinical remission, defined as absolute total Mayo Score and absolute Mayo endoscopy, stool frequency, rectal bleeding. Will be calculated using a modified Mayo score with the following: Stool Frequency (SF) sub score ≤ 1, with ≥ 1 point decrease from baseline, and Rectal Bleeding (RB) sub score = 0, and Endoscopic (ES) sub score ≤ 1 (modified, excludes friability) The modified Mayo score (0 to 9 points) is the sum of 3 components: the SF, RB, and ES sub scores Modified Mayo Score: The modified Mayo score is a 9-point scale; a score of 5 to 9 points (inclusive), which is required for randomization, denotes moderate to severe disease (by protocol definition). considered in clinical remission if a Mayo Score of less than or equal to 2 with no individual sub score greater than 1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Response Rate at 12 Weeks | From first dose to 12 weeks | Clinical response is defined as percentage of participants with a reduction in total Mayo Score and reduction in rectal bleeding subscore Will be defined as the following: A decrease from baseline in the modified Mayo score of ≥ 2 points, and A decrease from baseline in the modified Mayo score ≥ 30%, and A decrease in rectal bleeding(RB) subscore of ≥ 1 point or absolute RB subscore ≤ 1 |
| Endoscopic Response at Week 12 | up to 12 Weeks | Endoscopic response will be defined as percentage of participants with a reduction in the total Ulcerative Colitis Endoscopic Index of Severity score. The Ulcerative Colitis Endoscopic Index of Severity (UCEIS) scale: Vascular Pattern: * Normal (score 0) * patchy obliteration (score 1) * Obliterated (score 2) Bleeding * None (score 0) * Mucosal (score 1) * Luminal mild (score 2) * Luminal Moderate or severe (score 3) Erosions and Ulcers * None (score 0) * Erosions ( score 1) * Superficial Ulcer (2) * Deep Ulcer (score 3) A total score represents the following: remission (0-1); mild (2-4); moderate (5-6); and severe (7-8). |
| Histological Improvement Response Rate at 12 Weeks | up to 12 Weeks | Histologic improvement is defined as percentage of participants with a Geboes score of ≤ 3.1 Neutrophils \<5% of crypts, with no crypt destruction, erosions, ulcerations, and granulation tissue. Achieving the following scores for the corresponding grades of the Geboes score: * Score of 0 or 1 for Grade 3 (neutrophils in the epithelium: none or \< 5% crypts involved), and * Score of 0 for Grade 4 (crypt destruction: none), and * Score of 0 Grade 5 (erosion or ulceration: no erosions, ulcerations, or granulation tissue) grade 1 = chronic inflammatory infiltrate; grade 2 = lamina propria neutrophils and eosinophils; grade 3 = neutrophils in the epithelium; grade 4 = crypt destruction; grade 5 = erosions or ulceration. A higher score indicates more severe disease |
Countries
Australia, Belgium, Czechia, France, Germany, Hungary, Italy, Japan, Poland, Russia, South Korea, United Kingdom, United States
Participant flow
Pre-assignment details
131 Participants Randomized and 129 Treated
Participants by arm
| Arm | Count |
|---|---|
| Treatment BMS-986-165 6mg BID | 88 |
| Placebo Placebo | 43 |
| Total | 131 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 22 | 11 |
| Overall Study | Lack of Efficacy | 8 | 7 |
| Overall Study | Lost to Follow-up | 2 | 0 |
| Overall Study | Non-Compliance with Study Drug | 1 | 1 |
| Overall Study | Other Reasons | 5 | 5 |
| Overall Study | Pregnancy | 1 | 0 |
| Overall Study | Randomized but not treated | 1 | 1 |
| Overall Study | Withdrawal by Subject | 18 | 6 |
Baseline characteristics
| Characteristic | Total | Treatment | Placebo |
|---|---|---|---|
| Age, Continuous | 41.2 Years STANDARD_DEVIATION 14.48 | 41.6 Years STANDARD_DEVIATION 14.81 | 40.3 Years STANDARD_DEVIATION 13.91 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 3 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 124 Participants | 83 Participants | 41 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 10 Participants | 3 Participants | 7 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 5 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 114 Participants | 80 Participants | 34 Participants |
| Sex: Female, Male Female | 54 Participants | 40 Participants | 14 Participants |
| Sex: Female, Male Male | 77 Participants | 48 Participants | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 87 | 0 / 10 | 0 / 32 |
| other Total, other adverse events | 64 / 87 | 6 / 10 | 22 / 32 |
| serious Total, serious adverse events | 19 / 87 | 2 / 10 | 4 / 32 |
Outcome results
Primary
Clinical Remission Response Rate at Week 12
Clinical remission response rate is the percentage of participants achieving clinical remission, defined as absolute total Mayo Score and absolute Mayo endoscopy, stool frequency, rectal bleeding. Will be calculated using a modified Mayo score with the following: Stool Frequency (SF) sub score ≤ 1, with ≥ 1 point decrease from baseline, and Rectal Bleeding (RB) sub score = 0, and Endoscopic (ES) sub score ≤ 1 (modified, excludes friability) The modified Mayo score (0 to 9 points) is the sum of 3 components: the SF, RB, and ES sub scores Modified Mayo Score: The modified Mayo score is a 9-point scale; a score of 5 to 9 points (inclusive), which is required for randomization, denotes moderate to severe disease (by protocol definition). considered in clinical remission if a Mayo Score of less than or equal to 2 with no individual sub score greater than 1
Time frame: From first dose to 12 weeks.
Population: All Randomized Participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | Clinical Remission Response Rate at Week 12 | 14.8 Percentage of Participants |
| Placebo | Clinical Remission Response Rate at Week 12 | 16.3 Percentage of Participants |
p-value: 0.593595% CI: [0.3, 2.4]Stratified Cochran-Mantel-Haenszel
Secondary
Clinical Response Rate at 12 Weeks
Clinical response is defined as percentage of participants with a reduction in total Mayo Score and reduction in rectal bleeding subscore Will be defined as the following: A decrease from baseline in the modified Mayo score of ≥ 2 points, and A decrease from baseline in the modified Mayo score ≥ 30%, and A decrease in rectal bleeding(RB) subscore of ≥ 1 point or absolute RB subscore ≤ 1
Time frame: From first dose to 12 weeks
Population: All Randomized Participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | Clinical Response Rate at 12 Weeks | 37.5 Percentage of participants |
| Placebo | Clinical Response Rate at 12 Weeks | 32.6 Percentage of participants |
p-value: 0.305195% CI: [0.6, 2.7]Stratified Cochran-Mantel-Haenszel
Secondary
Endoscopic Response at Week 12
Endoscopic response will be defined as percentage of participants with a reduction in the total Ulcerative Colitis Endoscopic Index of Severity score. The Ulcerative Colitis Endoscopic Index of Severity (UCEIS) scale: Vascular Pattern: * Normal (score 0) * patchy obliteration (score 1) * Obliterated (score 2) Bleeding * None (score 0) * Mucosal (score 1) * Luminal mild (score 2) * Luminal Moderate or severe (score 3) Erosions and Ulcers * None (score 0) * Erosions ( score 1) * Superficial Ulcer (2) * Deep Ulcer (score 3) A total score represents the following: remission (0-1); mild (2-4); moderate (5-6); and severe (7-8).
Time frame: up to 12 Weeks
Population: All Randomized Participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | Endoscopic Response at Week 12 | 19.3 Percentage of Participants |
| Placebo | Endoscopic Response at Week 12 | 27.9 Percentage of Participants |
p-value: 0.876495% CI: [0.3, 1.4]Stratified Cochran-Mantel-Haenszel
Secondary
Histological Improvement Response Rate at 12 Weeks
Histologic improvement is defined as percentage of participants with a Geboes score of ≤ 3.1 Neutrophils \<5% of crypts, with no crypt destruction, erosions, ulcerations, and granulation tissue. Achieving the following scores for the corresponding grades of the Geboes score: * Score of 0 or 1 for Grade 3 (neutrophils in the epithelium: none or \< 5% crypts involved), and * Score of 0 for Grade 4 (crypt destruction: none), and * Score of 0 Grade 5 (erosion or ulceration: no erosions, ulcerations, or granulation tissue) grade 1 = chronic inflammatory infiltrate; grade 2 = lamina propria neutrophils and eosinophils; grade 3 = neutrophils in the epithelium; grade 4 = crypt destruction; grade 5 = erosions or ulceration. A higher score indicates more severe disease
Time frame: up to 12 Weeks
Population: All Randomized Participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | Histological Improvement Response Rate at 12 Weeks | 21.6 Percentage of Participants |
| Placebo | Histological Improvement Response Rate at 12 Weeks | 16.3 Percentage of Participants |
p-value: 0.223595% CI: [0.5, 3.8]Stratified Cochran-Mantel-Haenszel