Colitis, Ulcerative
Conditions
Brief summary
The purpose of this study is to assess the safety and tolerability, efficacy, and biomarker response of BMS-986165 administered orally in participants with moderate to severe ulcerative colitis. The study was originally designed to test deucravacitinib at two doses for 12 weeks compared to placebo. After the initial 12-Week period, all subjects receive active therapy (open-label extension). With protocol amendment 2, one of the dose treatment arms is being removed from the 12-week double blind period with no change to the open-label extension.
Interventions
DRUGBMS-986165
Specified Dose on Specified Days
OTHERPlacebo Comparator
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 65 Years
Healthy volunteers
No
Inclusion criteria
* Confirmed diagnosis of ulcerative colitis (UC) at least 3 months' duration prior to screening * Moderately to severely active UC as assessed by the modified Mayo score * Documentation of an inadequate response, loss of response, or intolerance to a treatment course of 1 or more of the following standard of care medications: oral 5-aminosalicylic acids, corticosteroids, immunomodulators, anti-tumor necrosis factor (TNF) agents, integrin inhibitors\[SA1\] * Documentation of prior treatment with corticosteroids for ≥ 4 weeks * Males and females must agree to follow specific methods of contraception, if applicable
Exclusion criteria
* Current diagnosis of Crohn's disease (CD) or diagnosis of indeterminate colitis (IC), ischemic colitis, or pseudomembranous colitis * Current evidence of fulminant colitis, abdominal abscess, toxic megacolon, or bowel perforation * History or evidence of any extensive colonic resection, or subtotal or total colectomy * Women who are pregnant or breastfeeding * Prior exposure to BMS-986165 or a tyrosine kinase 2 (TYK2) inhibitor Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants in Clinical Response at Week 12 | At week 12 | Clinical response is defined as achieving the following changes in the modified Mayo score (excludes the physicians' global assessment) * 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 Note: The modified Mayo score calculated to determine eligibility will also be used as the baseline disease activity score. The modified Mayo score is a 9-point scale (a score of 5 to 9 points denotes moderate to severe disease). The modified Mayo score is a sum of the following 3 components: * Stool frequency (SF) subscore (0 to 3) * Rectal bleeding (RB) subscore (0 to 3) * Endoscopic (ES) subscore (0 to 3) |
| Number of Participants Experiencing Adverse Events (AEs) | From first dose up to the last dose in the double-blind period or 30 days post the last dose date if not treated in the open-label period and from the first dose in open-label period up to 30 days post the last dose date (up to approximately 402 days) | An AE is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment. Note: the first dose of study treatment in the open-label period may be the same as the last dose date of study treatment in double-blind treatment period, therefore, the participants analyzed in the open-label period may contain double blind participants finishing their last dose in the double-blind treatment period. |
| Number of Participants Experiencing Serious Adverse Events (SAEs) | From first dose up to the last dose in the double-blind period or 30 days post the last dose date if not treated in the open-label period and from the first dose in open-label period up to 30 days post the last dose date (up to approximately 402 days) | An SAE is defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability or permanent damage, is a congenital anomaly/birth defect, is an important medical event. Note: the first dose of study treatment in the open-label period may be the same as the last dose date of study treatment in double-blind treatment period, therefore, the participants analyzed in the open-label period may contain double blind participants finishing their last dose in the double-blind treatment period. |
| Number of Participants Experiencing Adverse Events (AEs) Leading to Discontinuation | From first dose up to the last dose in the double-blind period or 30 days post the last dose date if not treated in the open-label period and from the first dose in open-label period up to 30 days post the last dose date (up to approximately 402 days) | An AE is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment. Note: the first dose of study treatment in the open-label period may be the same as the last dose date of study treatment in double-blind treatment period, therefore, the participants analyzed in the open-label period may contain double blind participants finishing their last dose in the double-blind treatment period. |
| Number of Participants Experiencing Adverse Events of Special Interest (AEIs) | From first dose to 52 weeks after first dose | An AE is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment. AEs of special interest include: skin events, influenza, herpes viral infections, opportunistic infections, tuberculosis, cardiovascular events, malignancy, and COVID-19. |
Countries
Australia, Canada, Germany, Netherlands, Poland, Puerto Rico, United Kingdom, United States
Participant flow
Pre-assignment details
BMS-986165 6 mg BID arm was removed under Protocol Amendment 02.
Participants by arm
| Arm | Count |
|---|---|
| BMS-986165 12 mg BID Participants receive BMS-986165 12 mg BID for a 12-week double-blind treatment period, then if eligible, move into the 40-week open-label extension period and receive BMS-986165 6 mg BID PO. | 26 |
| BMS-986165 6 mg BID Participants were randomized to the 6 mg BID arm under the Original Protocol or Protocol Amendment 01 receive 6 mg BID for the 12-week double-blind treatment period and 6 mg BID in the open-label extension period. | 4 |
| Placebo BID PO Participants receive placebo for a 12-week double-blind treatment period, then if eligible, move into the 40-week open-label extension period and receive BMS-986165 6 mg BID PO. | 8 |
| Total | 38 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Double-Blind Treatment Period | Adverse Event | 2 | 0 | 1 |
| Double-Blind Treatment Period | Lack of Efficacy | 1 | 0 | 0 |
| Double-Blind Treatment Period | Other Reasons | 2 | 0 | 0 |
| Double-Blind Treatment Period | Participant request to discontinue treatment | 1 | 0 | 0 |
| Double-Blind Treatment Period | Participant withdrew consent | 1 | 1 | 0 |
| Open-Label Treatment Period | Administrative reason by sponsor | 4 | 0 | 0 |
| Open-Label Treatment Period | Adverse Event | 1 | 0 | 3 |
| Open-Label Treatment Period | Lack of Efficacy | 0 | 3 | 0 |
| Open-Label Treatment Period | Other reasons | 1 | 0 | 0 |
| Open-Label Treatment Period | Participant request to discontinue treatment | 1 | 0 | 0 |
| Open-Label Treatment Period | Participant withdrew consent | 1 | 0 | 3 |
Baseline characteristics
| Characteristic | BMS-986165 12 mg BID | BMS-986165 6 mg BID | Placebo BID PO | Total |
|---|---|---|---|---|
| Age, Continuous | 41.8 Years STANDARD_DEVIATION 14.4 | 28.8 Years STANDARD_DEVIATION 6.7 | 38.0 Years STANDARD_DEVIATION 15.1 | 39.6 Years STANDARD_DEVIATION 14.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants | 3 Participants | 6 Participants | 33 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 1 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 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 | 25 Participants | 3 Participants | 7 Participants | 35 Participants |
| Sex: Female, Male Female | 12 Participants | 2 Participants | 2 Participants | 16 Participants |
| Sex: Female, Male Male | 14 Participants | 2 Participants | 6 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 26 | 0 / 4 | 0 / 8 | 0 / 29 |
| other Total, other adverse events | 19 / 26 | 4 / 4 | 6 / 8 | 20 / 29 |
| serious Total, serious adverse events | 4 / 26 | 0 / 4 | 1 / 8 | 2 / 29 |
Outcome results
Primary
Number of Participants Experiencing Adverse Events (AEs)
An AE is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment. Note: the first dose of study treatment in the open-label period may be the same as the last dose date of study treatment in double-blind treatment period, therefore, the participants analyzed in the open-label period may contain double blind participants finishing their last dose in the double-blind treatment period.
Time frame: From first dose up to the last dose in the double-blind period or 30 days post the last dose date if not treated in the open-label period and from the first dose in open-label period up to 30 days post the last dose date (up to approximately 402 days)
Population: All randomized participants who receive at least 1 dose of double-blind study treatment. Prespecified to be collected for participants in Arms BMS-986165 12 mg BID and Placebo BID PO. BMS-986165 6 mg BID was removed under Protocol Amendment 02.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BMS-986165 12 mg BID | Number of Participants Experiencing Adverse Events (AEs) | Double-Blind Treatment Period | 21 Participants |
| BMS-986165 12 mg BID | Number of Participants Experiencing Adverse Events (AEs) | Open-Label Treatment Period | 15 Participants |
| Placebo BID PO | Number of Participants Experiencing Adverse Events (AEs) | Double-Blind Treatment Period | 6 Participants |
| Placebo BID PO | Number of Participants Experiencing Adverse Events (AEs) | Open-Label Treatment Period | 6 Participants |
Primary
Number of Participants Experiencing Adverse Events (AEs) Leading to Discontinuation
An AE is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment. Note: the first dose of study treatment in the open-label period may be the same as the last dose date of study treatment in double-blind treatment period, therefore, the participants analyzed in the open-label period may contain double blind participants finishing their last dose in the double-blind treatment period.
Time frame: From first dose up to the last dose in the double-blind period or 30 days post the last dose date if not treated in the open-label period and from the first dose in open-label period up to 30 days post the last dose date (up to approximately 402 days)
Population: All randomized participants who receive at least 1 dose of double-blind study treatment. Prespecified to be collected for participants in Arms BMS-986165 12 mg BID and Placebo BID PO. BMS-986165 6 mg BID was removed under Protocol Amendment 02.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BMS-986165 12 mg BID | Number of Participants Experiencing Adverse Events (AEs) Leading to Discontinuation | Double-Blind Treatment Period | 2 Participants |
| BMS-986165 12 mg BID | Number of Participants Experiencing Adverse Events (AEs) Leading to Discontinuation | Open-Label Treatment Period | 1 Participants |
| Placebo BID PO | Number of Participants Experiencing Adverse Events (AEs) Leading to Discontinuation | Double-Blind Treatment Period | 0 Participants |
| Placebo BID PO | Number of Participants Experiencing Adverse Events (AEs) Leading to Discontinuation | Open-Label Treatment Period | 3 Participants |
Primary
Number of Participants Experiencing Adverse Events of Special Interest (AEIs)
An AE is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment. AEs of special interest include: skin events, influenza, herpes viral infections, opportunistic infections, tuberculosis, cardiovascular events, malignancy, and COVID-19.
Time frame: From first dose to 52 weeks after first dose
Population: All randomized participants who receive at least 1 dose of double-blind study treatment. Prespecified to be collected for participants in Arms BMS-986165 12 mg BID and Placebo BID PO. BMS-986165 6 mg BID was removed under Protocol Amendment 02.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BMS-986165 12 mg BID | Number of Participants Experiencing Adverse Events of Special Interest (AEIs) | Skin Events | 15 Participants |
| BMS-986165 12 mg BID | Number of Participants Experiencing Adverse Events of Special Interest (AEIs) | Tuberculosis | 0 Participants |
| BMS-986165 12 mg BID | Number of Participants Experiencing Adverse Events of Special Interest (AEIs) | Herpes Viral Infections | 0 Participants |
| BMS-986165 12 mg BID | Number of Participants Experiencing Adverse Events of Special Interest (AEIs) | Cardiovascular events | 1 Participants |
| BMS-986165 12 mg BID | Number of Participants Experiencing Adverse Events of Special Interest (AEIs) | Malignancy | 0 Participants |
| BMS-986165 12 mg BID | Number of Participants Experiencing Adverse Events of Special Interest (AEIs) | Influenza | 1 Participants |
| BMS-986165 12 mg BID | Number of Participants Experiencing Adverse Events of Special Interest (AEIs) | Opportunistic Infections | 0 Participants |
| BMS-986165 12 mg BID | Number of Participants Experiencing Adverse Events of Special Interest (AEIs) | COVID-19 | 3 Participants |
| Placebo BID PO | Number of Participants Experiencing Adverse Events of Special Interest (AEIs) | Opportunistic Infections | 0 Participants |
| Placebo BID PO | Number of Participants Experiencing Adverse Events of Special Interest (AEIs) | Skin Events | 5 Participants |
| Placebo BID PO | Number of Participants Experiencing Adverse Events of Special Interest (AEIs) | Influenza | 2 Participants |
| Placebo BID PO | Number of Participants Experiencing Adverse Events of Special Interest (AEIs) | Herpes Viral Infections | 0 Participants |
| Placebo BID PO | Number of Participants Experiencing Adverse Events of Special Interest (AEIs) | Cardiovascular events | 0 Participants |
| Placebo BID PO | Number of Participants Experiencing Adverse Events of Special Interest (AEIs) | Tuberculosis | 0 Participants |
| Placebo BID PO | Number of Participants Experiencing Adverse Events of Special Interest (AEIs) | Malignancy | 0 Participants |
| Placebo BID PO | Number of Participants Experiencing Adverse Events of Special Interest (AEIs) | COVID-19 | 0 Participants |
Primary
Number of Participants Experiencing Serious Adverse Events (SAEs)
An SAE is defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability or permanent damage, is a congenital anomaly/birth defect, is an important medical event. Note: the first dose of study treatment in the open-label period may be the same as the last dose date of study treatment in double-blind treatment period, therefore, the participants analyzed in the open-label period may contain double blind participants finishing their last dose in the double-blind treatment period.
Time frame: From first dose up to the last dose in the double-blind period or 30 days post the last dose date if not treated in the open-label period and from the first dose in open-label period up to 30 days post the last dose date (up to approximately 402 days)
Population: All randomized participants who receive at least 1 dose of double-blind study treatment. Prespecified to be collected for participants in Arms BMS-986165 12 mg BID and Placebo BID PO. BMS-986165 6 mg BID was removed under Protocol Amendment 02.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BMS-986165 12 mg BID | Number of Participants Experiencing Serious Adverse Events (SAEs) | Double-Blind Treatment Period | 4 Participants |
| BMS-986165 12 mg BID | Number of Participants Experiencing Serious Adverse Events (SAEs) | Open-Label Treatment Period | 1 Participants |
| Placebo BID PO | Number of Participants Experiencing Serious Adverse Events (SAEs) | Double-Blind Treatment Period | 1 Participants |
| Placebo BID PO | Number of Participants Experiencing Serious Adverse Events (SAEs) | Open-Label Treatment Period | 1 Participants |
Primary
Percentage of Participants in Clinical Response at Week 12
Clinical response is defined as achieving the following changes in the modified Mayo score (excludes the physicians' global assessment) * 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 Note: The modified Mayo score calculated to determine eligibility will also be used as the baseline disease activity score. The modified Mayo score is a 9-point scale (a score of 5 to 9 points denotes moderate to severe disease). The modified Mayo score is a sum of the following 3 components: * Stool frequency (SF) subscore (0 to 3) * Rectal bleeding (RB) subscore (0 to 3) * Endoscopic (ES) subscore (0 to 3)
Time frame: At week 12
Population: Prespecified to be collected for all randomized participants in Arms BMS-986165 12 mg BID and Placebo BID PO. BMS-986165 6 mg BID was removed under Protocol Amendment 02.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BMS-986165 12 mg BID | Percentage of Participants in Clinical Response at Week 12 | 53.8 Percentage of participants |
| Placebo BID PO | Percentage of Participants in Clinical Response at Week 12 | 50.0 Percentage of participants |
95% CI: [-35.7, 43.4]