Crohn's Disease, Crohn's Enteritis, Granulomatous Colitis, Granulomatous Enteritis
Conditions
Brief summary
The purpose of this study is to assess the safety and effectiveness of BMS-986165 compared to placebo in participants with moderately to severely active Crohn's Disease.
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 75 Years
Healthy volunteers
No
Inclusion criteria
* Documented diagnosis of Crohn's Disease (CD) for at least 3 months prior to screening, including ileal, colonic, or ileo-colonic disease distribution * Must have had an inadequate response, loss of response, or intolerance to 1 or more of the standard treatments * Must have active moderate to severe CD * Men and women must agree to follow specific methods of contraception, if applicable
Exclusion criteria
* Severe or fulminant colitis that is likely to require surgery or hospitalization * Presence of a diagnosis of alternative forms of colitis (infectious, inflammatory including ulcerative colitis, malignant, toxic, indeterminate, etc.) other than Crohn's Disease * Previous exposure to BMS-986165 in any study * Any major illness/condition or evidence of an unstable clinical condition (eg, renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, immunologic, psychiatric, or local active infection/infectious illness) that, in the investigator's judgment, will substantially increase the risk to the participant Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Participants Achieving Clinical Remission at Week 12 | 12 weeks after first dose | Percent of participants achieving clinical remission at Week 12. Clinical remission is defined as achieving a Crohn's Disease Activity Index (CDAI) Score below 150. CDAI is a tool that helps doctors measure how severe someone's Crohn's disease is. It uses questions about symptoms experienced over a week to calculate a score. The scores range from 0 to 600 and are classified into different categories. Scores from 0 to 149 suggest the disease may be in remission. Scores from 150 to 220 indicate mild activity. Scores from 220 to 450 mean the disease is moderate to severe. Scores from 451 to 600 indicate severe disease. Higher scores mean more severe symptoms. Risk Difference and Odds Ratio prespecified to be collected for 3 mg and 6 mg BMS-986165 arms only. |
| Percent of Participants Achieving Endoscopic Response at Week 12 | 12 weeks after first dose | Endoscopic Response is defined as \>= 50% decrease from baseline in the Simple Endoscopic Score for Crohn's Disease (SES-CD). The SES-CD score is a way to measure how severe a person's bowel disease is. It looks at five different parts of the bowel and checks for things like ulcers and inflammation. Each part is given a score from 0 to 3 based on how bad the disease is. These scores are then added together for a total score ranging from 0 to 60. Higher scores indicate more severe disease. Baseline refers to the initial set of before data collected from participants before starting study treatment. Risk Difference and Odds Ratio prespecified to be collected for 3 mg and 6 mg BMS-986165 arms only. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Participants Achieving Clinical Response at Week 12 | 12 weeks after first dose | Clinical response is defined as a reduction from baseline in the Crohn's Disease Activity Index (CDAI) score of ≥ 100 points or a total CDAI score \< 150. CDAI is a tool that helps doctors measure how severe someone's Crohn's disease is. It uses questions about symptoms experienced over a week to calculate a score. The scores range from 0 to 600 and are classified into different categories. Scores from 0 to 149 suggest the disease may be in remission. Scores from 150 to 220 indicate mild activity. Scores from 220 to 450 mean the disease is moderate to severe. Scores from 451 to 600 indicate severe disease. Higher scores mean more severe symptoms. Baseline refers to the initial set of before data collected from participants before starting study treatment. Risk Difference and Odds Ratio prespecified to be collected for 3 mg and 6 mg BMS-986165 arms only. |
| Percent of Participants Who Achieving Patient Reported Outcomes 2 (PRO2) Remission at Week 12 | 12 weeks after first dose | The Patient Reported Outcomes 2 (PRO2) is a way for patients to report how they're feeling. It focuses on two things: how often they have loose or liquid stools, and how much abdominal pain they have. They keep track of these things every day for a week. Stool frequency is rated on a scale from 0 to 3, with 0 being the normal number of stools per day to 3 which is \>/=5 stools more than normal per day. The pain is rated on a scale from 0 to 3, with 0 being no pain and 3 being severe pain. The scores for these two things are added up to get a total score ranging from 0-6. If the average daily score for abdominal pain is 1 or less, and the average number of loose or liquid stools is 3 or less, then the disease might be in remission. Risk Difference and Odds Ratio prespecified to be collected for 3 mg and 6 mg BMS-986165 arms only. |
| Change From Baseline in Simple Endoscopic Score for Crohn's Disease (SES-CD) at Week 12 | 12 weeks after first dose | The SES-CD score is a way to measure how severe a person's bowel disease is. It looks at five different parts of the bowel and checks for ulcer size, ulcerated surface, inflamed surface, and stenosis. Each is given a score from 0 to 3 based on how bad the disease is. These scores are then added together for a total score ranging from 0 to 60. Higher scores indicate more severe disease. Baseline refers to the initial set of before data collected from participants starting study treatment. |
Countries
Australia, Belgium, Brazil, Canada, China, Czechia, Denmark, France, Germany, Hungary, Ireland, Israel, Italy, Japan, Mexico, Netherlands, Poland, Portugal, Romania, Russia, South Korea, Spain, Switzerland, Taiwan, United Kingdom, United States
Participant flow
Recruitment details
This study has a treat-through design
Pre-assignment details
Enrollment into the 12 mg BMS-986165 arm was discontinued. Participants who were randomized to 12 mg BMS-986165 continued on their originally assigned double-blind study treatment. These participants completed all study procedures and assessments outlined in the current version of the protocol.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo was taken twice per day over 12 weeks. Participants who achieved a clinical response after week 12 continued to take placebo twice daily until the end of week 52. Participants who did not achieve clinical response at week 12 but had an appropriate safety profile were eligible to receive open-label BMS-986165 6 mg twice per day until week 52. Week 12 responders (Placebo) and week 12 non-responders (BMS-986165 6 mg OL) who continued to derive a clinical benefit from their respective treatments at week 26/52 and week 52 respectively were eligible to receive BMS-986165 6 mg twice daily for up week 104. | 60 |
| 3 mg BMS-986165 BMS-986165 3 mg was taken orally twice per day over 12 weeks. Participants who achieved a clinical response after the week 12 continued to take BMS-986165 3 mg orally twice daily until the end of week 52. Participants who did not achieve clinical response at week 12 but had an appropriate safety profile were eligible to receive BMS-986165 6 mg twice per day until week 52. Week 12 responders (BMS-986165 3 mg) and week 12 non-responders (BMS-986165 6 mg OL) who continued to derive a clinical benefit from their respective treatments at week 26/52 and week 52 respectively were eligible to receive open label BMS-986165 6 mg twice daily for up to week 104. | 86 |
| 6 mg BMS-986165 BMS-986165 6 mg was taken orally twice per day over 12 weeks. Participants who achieved a clinical response after the week 12 continued to take BMS-986165 6 mg orally twice daily until the end of week 52. Participants who did not achieve clinical response at week 12 but had an appropriate safety profile were eligible to receive BMS-986165 6 mg twice per day until week 52. Week 12 responders and week 12 non-responders who continued to derive a clinical benefit from their respective treatments at week 26/52 and week 52 respectively were eligible to receive open label BMS-986165 6 mg twice daily up to week 104. | 84 |
| 12 mg BMS-986165 BMS-986165 12 mg was taken orally once per day over 12 weeks. Participants who achieved a clinical response after week 12 continued to take BMS-986165 12 mg orally once daily until the end of week 52. Participants who did not achieve clinical response prior to protocol v 3 but had an appropriate safety profile were eligible to receive BMS-986165 12 mg once per day. Participants who were randomized prior to the implementation of Protocol v3.0 who had not yet reached Week 12 but had an appropriate safety profile could switch to open-label BMS-986165 6 mg until week 52, if they did not achieve a clinical response at Week 12. Week 12 responders and week 12 non-responders who continued to derive a clinical benefit from their respective treatments at week 26/52 and week 52 respectively were eligible to receive open label BMS-986165 6 mg twice daily until week 104. | 9 |
| Total | 239 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Pre-Treatment Period | Other reasons | 1 | 1 | 1 | 0 |
| Pre-Treatment Period | Withdrawal by Subject | 0 | 1 | 0 | 0 |
| Treatment Period | Adverse Event | 11 | 20 | 18 | 2 |
| Treatment Period | Lack of Efficacy | 18 | 12 | 13 | 2 |
| Treatment Period | Lost to Follow-up | 1 | 0 | 0 | 0 |
| Treatment Period | Other reasons | 4 | 6 | 7 | 0 |
| Treatment Period | Site terminated by sponsor | 0 | 1 | 0 | 0 |
| Treatment Period | Study terminated by sponsor | 7 | 20 | 15 | 0 |
| Treatment Period | Withdrawal by Subject | 5 | 11 | 16 | 1 |
Baseline characteristics
| Characteristic | Placebo | 3 mg BMS-986165 | 6 mg BMS-986165 | 12 mg BMS-986165 | Total |
|---|---|---|---|---|---|
| Age, Continuous | 39.1 Years STANDARD_DEVIATION 16.7 | 39.5 Years STANDARD_DEVIATION 15.2 | 37.9 Years STANDARD_DEVIATION 14.6 | 37.4 Years STANDARD_DEVIATION 13.7 | 38.8 Years STANDARD_DEVIATION 15.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 7 Participants | 2 Participants | 0 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 58 Participants | 78 Participants | 80 Participants | 9 Participants | 225 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Asian | 11 Participants | 13 Participants | 12 Participants | 1 Participants | 37 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 1 Participants | 3 Participants | 0 Participants | 5 Participants |
| Race/Ethnicity, Customized Not Reported | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 48 Participants | 70 Participants | 68 Participants | 8 Participants | 194 Participants |
| Sex: Female, Male Female | 22 Participants | 38 Participants | 34 Participants | 3 Participants | 97 Participants |
| Sex: Female, Male Male | 38 Participants | 48 Participants | 50 Participants | 6 Participants | 142 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 / 60 | 0 / 86 | 0 / 84 | 0 / 9 | 0 / 161 | 0 / 6 |
| other Total, other adverse events | 33 / 59 | 55 / 84 | 55 / 83 | 7 / 9 | 86 / 161 | 3 / 6 |
| serious Total, serious adverse events | 6 / 59 | 11 / 84 | 5 / 83 | 2 / 9 | 15 / 161 | 1 / 6 |
Outcome results
Primary
Percent of Participants Achieving Clinical Remission at Week 12
Percent of participants achieving clinical remission at Week 12. Clinical remission is defined as achieving a Crohn's Disease Activity Index (CDAI) Score below 150. CDAI is a tool that helps doctors measure how severe someone's Crohn's disease is. It uses questions about symptoms experienced over a week to calculate a score. The scores range from 0 to 600 and are classified into different categories. Scores from 0 to 149 suggest the disease may be in remission. Scores from 150 to 220 indicate mild activity. Scores from 220 to 450 mean the disease is moderate to severe. Scores from 451 to 600 indicate severe disease. Higher scores mean more severe symptoms. Risk Difference and Odds Ratio prespecified to be collected for 3 mg and 6 mg BMS-986165 arms only.
Time frame: 12 weeks after first dose
Population: All randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percent of Participants Achieving Clinical Remission at Week 12 | 28.3 Percent of Participants |
| 3 mg BMS-986165 | Percent of Participants Achieving Clinical Remission at Week 12 | 32.6 Percent of Participants |
| 6 mg BMS-986165 | Percent of Participants Achieving Clinical Remission at Week 12 | 21.4 Percent of Participants |
| 12 mg BMS-986165 | Percent of Participants Achieving Clinical Remission at Week 12 | 22.2 Percent of Participants |
p-value: 0.581295% CI: [-11, 19.5]Mantel Haenszel
p-value: 0.581295% CI: [0.6, 2.5]Mantel Haenszel
p-value: 0.37295% CI: [-20.2, 7.6]Mantel Haenszel
p-value: 0.37295% CI: [0.3, 1.5]Mantel Haenszel
Primary
Percent of Participants Achieving Endoscopic Response at Week 12
Endoscopic Response is defined as \>= 50% decrease from baseline in the Simple Endoscopic Score for Crohn's Disease (SES-CD). The SES-CD score is a way to measure how severe a person's bowel disease is. It looks at five different parts of the bowel and checks for things like ulcers and inflammation. Each part is given a score from 0 to 3 based on how bad the disease is. These scores are then added together for a total score ranging from 0 to 60. Higher scores indicate more severe disease. Baseline refers to the initial set of before data collected from participants before starting study treatment. Risk Difference and Odds Ratio prespecified to be collected for 3 mg and 6 mg BMS-986165 arms only.
Time frame: 12 weeks after first dose
Population: All randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percent of Participants Achieving Endoscopic Response at Week 12 | 8.3 Percent of Participants |
| 3 mg BMS-986165 | Percent of Participants Achieving Endoscopic Response at Week 12 | 23.3 Percent of Participants |
| 6 mg BMS-986165 | Percent of Participants Achieving Endoscopic Response at Week 12 | 16.7 Percent of Participants |
| 12 mg BMS-986165 | Percent of Participants Achieving Endoscopic Response at Week 12 | 33.3 Percent of Participants |
p-value: 0.019895% CI: [3.7, 26.3]Mantel Haenszel
p-value: 0.019895% CI: [1.2, 9.8]Mantel Haenszel
p-value: 0.158495% CI: [-2.6, 19]Mantel Haenszel
p-value: 0.158495% CI: [0.7, 6.1]Mantel Haenszel
Secondary
Change From Baseline in Simple Endoscopic Score for Crohn's Disease (SES-CD) at Week 12
The SES-CD score is a way to measure how severe a person's bowel disease is. It looks at five different parts of the bowel and checks for ulcer size, ulcerated surface, inflamed surface, and stenosis. Each is given a score from 0 to 3 based on how bad the disease is. These scores are then added together for a total score ranging from 0 to 60. Higher scores indicate more severe disease. Baseline refers to the initial set of before data collected from participants starting study treatment.
Time frame: 12 weeks after first dose
Population: All randomized participants with available baseline and week 12 SES-CD scores.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Simple Endoscopic Score for Crohn's Disease (SES-CD) at Week 12 | -1.5 Change in Score on a Scale | Standard Deviation 4.3 |
| 3 mg BMS-986165 | Change From Baseline in Simple Endoscopic Score for Crohn's Disease (SES-CD) at Week 12 | -2.5 Change in Score on a Scale | Standard Deviation 6.5 |
| 6 mg BMS-986165 | Change From Baseline in Simple Endoscopic Score for Crohn's Disease (SES-CD) at Week 12 | -3.7 Change in Score on a Scale | Standard Deviation 5.5 |
| 12 mg BMS-986165 | Change From Baseline in Simple Endoscopic Score for Crohn's Disease (SES-CD) at Week 12 | -5.6 Change in Score on a Scale | Standard Deviation 8.5 |
95% CI: [-4.3, -1.8]ANCOVA
p-value: 0.042895% CI: [-3.7, -0.1]ANCOVA
95% CI: [-4.8, -2]ANCOVA
p-value: 0.017795% CI: [-4.1, -0.4]ANCOVA
95% CI: [-2.6, 0.3]
95% CI: [-9.7, -2.3]ANCOVA
Secondary
Percent of Participants Achieving Clinical Response at Week 12
Clinical response is defined as a reduction from baseline in the Crohn's Disease Activity Index (CDAI) score of ≥ 100 points or a total CDAI score \< 150. CDAI is a tool that helps doctors measure how severe someone's Crohn's disease is. It uses questions about symptoms experienced over a week to calculate a score. The scores range from 0 to 600 and are classified into different categories. Scores from 0 to 149 suggest the disease may be in remission. Scores from 150 to 220 indicate mild activity. Scores from 220 to 450 mean the disease is moderate to severe. Scores from 451 to 600 indicate severe disease. Higher scores mean more severe symptoms. Baseline refers to the initial set of before data collected from participants before starting study treatment. Risk Difference and Odds Ratio prespecified to be collected for 3 mg and 6 mg BMS-986165 arms only.
Time frame: 12 weeks after first dose
Population: All randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percent of Participants Achieving Clinical Response at Week 12 | 40.0 Percent of Participants |
| 3 mg BMS-986165 | Percent of Participants Achieving Clinical Response at Week 12 | 47.7 Percent of Participants |
| 6 mg BMS-986165 | Percent of Participants Achieving Clinical Response at Week 12 | 38.1 Percent of Participants |
| 12 mg BMS-986165 | Percent of Participants Achieving Clinical Response at Week 12 | 55.6 Percent of Participants |
p-value: 0.346495% CI: [-8.2, 23.6]Mantel Haenszel
p-value: 0.346495% CI: [0.7, 2.8]Mantel Haenszel
p-value: 0.885795% CI: [-17, 14.7]Mantel Haenszel
p-value: 0.885795% CI: [0.5, 1.9]Mantel Haenszel
Secondary
Percent of Participants Who Achieving Patient Reported Outcomes 2 (PRO2) Remission at Week 12
The Patient Reported Outcomes 2 (PRO2) is a way for patients to report how they're feeling. It focuses on two things: how often they have loose or liquid stools, and how much abdominal pain they have. They keep track of these things every day for a week. Stool frequency is rated on a scale from 0 to 3, with 0 being the normal number of stools per day to 3 which is \>/=5 stools more than normal per day. The pain is rated on a scale from 0 to 3, with 0 being no pain and 3 being severe pain. The scores for these two things are added up to get a total score ranging from 0-6. If the average daily score for abdominal pain is 1 or less, and the average number of loose or liquid stools is 3 or less, then the disease might be in remission. Risk Difference and Odds Ratio prespecified to be collected for 3 mg and 6 mg BMS-986165 arms only.
Time frame: 12 weeks after first dose
Population: All randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percent of Participants Who Achieving Patient Reported Outcomes 2 (PRO2) Remission at Week 12 | 25.0 Percent of Participants |
| 3 mg BMS-986165 | Percent of Participants Who Achieving Patient Reported Outcomes 2 (PRO2) Remission at Week 12 | 32.6 Percent of Participants |
| 6 mg BMS-986165 | Percent of Participants Who Achieving Patient Reported Outcomes 2 (PRO2) Remission at Week 12 | 20.2 Percent of Participants |
| 12 mg BMS-986165 | Percent of Participants Who Achieving Patient Reported Outcomes 2 (PRO2) Remission at Week 12 | 33.3 Percent of Participants |
p-value: 0.284195% CI: [-6.7, 22.9]Mantel Haenszel
p-value: 0.284195% CI: [0.7, 3.1]Mantel Haenszel
p-value: 0.541795% CI: [-17.6, 9.2]Mantel Haenszel
p-value: 0.541795% CI: [0.3, 1.8]Mantel Haenszel