Psoriasis
Conditions
Brief summary
A Study to evaluate efficacy and safety in subjects with moderate to severe Psoriasis treated with BMS-986165
Interventions
DRUGBMS-986165
DRUGPlacebo for BMS-986165
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: * Male and female, ages 18 to 70 years * Diagnosis of plaque psoriasis for 6 months * Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test, must not be pregnant, lactating, breastfeeding or planning pregnancy * Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment plus 5 half-lives of the study drug plus 90 days.
Exclusion criteria
* Any significant acute or chronic medical illness * Blood transfusion within 4 weeks of study drug administration * Inability to tolerate oral medication * Positive hepatitis-B (HBV) surface antigen * Positive hepatitis-C (HCV) antibody * Any history or risk for tuberculosis (TB) * Any major illness/condition or evidence of an unstable clinical condition * Chest X-ray findings suspicious of infection at screening * has received ustekinumab, secukinumab or ixekizumab within 6 months of first administration of study medication * Has received anti-Tumor Necrosis Factor (TNF) inhibitor(s) within 2 months of first administration of study medication * Has received Rituximab within 6 months of first administration of study medication * Topical medications/treatments for psoriasis within 2 weeks of the first administration of any study medication * Any systemic medications/treatments for psoriasis within 4 weeks of the first administration of any study medication Other protocol defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Percentage of Participants With Moderate to Severe Psoriasis Experiencing a 75% Improvement (Reduction From Baseline) in PASI Score (PASI-75 Response Rate) on Day 85 (Week 12) | Day 1 to Day 85 | Psoriasis Area and Severity Index (PASI) 75 response: patients who achieved ≥ 75% improvement (reduction) in PASI score compared to baseline were defined as PASI 75 responders. PASI scores can range from 0, corresponding to no signs of psoriasis up to theoretical maximum of 72.0, which means a higher PASI score reflects a higher psoriasis activity. |
| Number of Participants With Adverse Events | Day 1 to day 115 | The safety and tolerability of BMS-986195 as assessed by the number of subjects with adverse events (AEs); number of subjects with serious adverse events (SAEs); number of subjects with adverse events leading to discontinuation |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in DLQI Scores on Day 85 | Day 1 to Day 85 | The DLQI is a participant reported quality of life index which consists of 10 questions concerning symptoms and feelings, daily activities, leisure, work, school, personal relationships, and treatment during the last week. Each question is scored on a scale of 0 to 3 by a tick box: not at all, a little, a lot, or very much. The scores are summed, giving a range from 0 (no impairment of life quality) to 30 (maximum impairment) |
| Percentage of Participants on Day 85 With PASI-50, PASI-90, PASI-100. | Day 1 to Day 85 | Percentage of patients achieving Psoriasis Area and Severity Index (PASI) 50, PASI 90 and PASI 100 responses on Day 85. PASI 50 response: patients who achieved ≥ 50% improvement (reduction) in PASI score compared to baseline were defined as PASI 50 responders. PASI 90 response: patients who achieved ≥ 90% improvement (reduction) in PASI score compared to baseline were defined as PASI 90 responders. PASI 100 response: patients who achieved ≥ 100% improvement (reduction) in PASI score compared to baseline were defined as PASI 100 responders. PASI scores can range from 0, corresponding to no signs of psoriasis up to theoretical maximum of 72.0, which means a higher PASI score reflects a higher psoriasis activity. |
| Trough Observed Plasma Concentration of BMS-986165 (Ctrough) | Days 8, 15, 29, 57, 85 | Pharmacokinetics of BMS-986165 were derived from plasma concentration versus time data. Ctrough= Trough observed plasma concentration |
| Change From Baseline in BSA on Day 85 | Day 1 to Day 85 | Measurement of psoriasis body surface area (BSA) involvement is estimated using the handprint method with the size of a patient's handprint representing \ 1% of body surface area involved.The total BSA = 100% with breakdown by body region as follows: head and neck = 10% (10 handprints), upper extremities = 20% (20 handprints), trunk including axillae and groin = 30% (30 handprints), lower extremities including buttocks = 40% (40 handprints). A decrease from Baseline indicates improvement. Change from Baseline was calculated as Baseline score - Day 85 score; a positive change from Baseline therefore indicates improvement. |
| Percentage of Participants on Day 85 With sPGA Score of 0 or 1 (sPGA0/1 Response Rate). | Day 1 to Day 85 | Percentage of participants achieving a clear (0) or almost clear (1) status on the Static Physician Global Assessment (sPGA) on Day 85. This index evaluates the physician's global assessment of the participant's psoriasis based on severity of induration, scaling, and erythema. The assessment was scored on a scale of 0 to 5, where 0 = clear, with no evidence of plaque elevation, erythema, or scale, and 5 = severe induration, erythema, and scaling. |
Countries
Australia, Canada, Germany, Japan, Latvia, Mexico, Poland, United States
Participant flow
Pre-assignment details
268 participants were randomized in the study; One participant was randomized but did not receive study drug due to being lost to follow-up
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo for BMS-986165 | 45 |
| BMS-986165 3MG QOD BMS-986165 3mg capsules Every Other Day | 44 |
| BMS-986165 3MG QD BMS-986165 3 mg capsules every day | 44 |
| BMS-986165 3MG BID BMS-986165 3 mg capsules twice daily | 45 |
| BMS-986165 6MG BID BMS-986165 6 mg capsules twice daily | 45 |
| BMS-986165 12MG QD BMS-986165 12 mg capsules every day | 44 |
| Total | 267 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 | 2 | 1 | 3 | 1 |
| Overall Study | Lack of Efficacy | 5 | 4 | 0 | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 1 | 0 | 1 | 1 | 2 | 0 |
| Overall Study | Poor/non-compliance | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Reason not provided by investigator | 1 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Subject request to discontinue treatment | 4 | 3 | 3 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 2 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo | Total | BMS-986165 12MG QD | BMS-986165 6MG BID | BMS-986165 3MG BID | BMS-986165 3MG QD | BMS-986165 3MG QOD |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 46.4 Years STANDARD_DEVIATION 11.93 | 44.6 Years STANDARD_DEVIATION 12.96 | 46.6 Years STANDARD_DEVIATION 11.62 | 42.8 Years STANDARD_DEVIATION 12.9 | 45.6 Years STANDARD_DEVIATION 15.1 | 45.0 Years STANDARD_DEVIATION 13.77 | 41.0 Years STANDARD_DEVIATION 11.8 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 3 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 36 Participants | 6 Participants | 9 Participants | 5 Participants | 5 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 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 | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 40 Participants | 225 Participants | 37 Participants | 35 Participants | 39 Participants | 39 Participants | 35 Participants |
| Sex: Female, Male Female | 8 Participants | 73 Participants | 14 Participants | 10 Participants | 19 Participants | 14 Participants | 8 Participants |
| Sex: Female, Male Male | 37 Participants | 194 Participants | 30 Participants | 35 Participants | 26 Participants | 30 Participants | 36 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 / 45 | 0 / 44 | 0 / 44 | 0 / 45 | 0 / 45 | 0 / 44 |
| other Total, other adverse events | 13 / 45 | 14 / 44 | 18 / 44 | 15 / 45 | 25 / 45 | 19 / 44 |
| serious Total, serious adverse events | 1 / 45 | 1 / 44 | 1 / 44 | 1 / 45 | 0 / 45 | 0 / 44 |
Outcome results
Primary
Number of Participants With Adverse Events
The safety and tolerability of BMS-986195 as assessed by the number of subjects with adverse events (AEs); number of subjects with serious adverse events (SAEs); number of subjects with adverse events leading to discontinuation
Time frame: Day 1 to day 115
Population: All Randomized and Treated Participants
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Adverse Events | No. of participants with AEs | 24 Participants |
| Placebo | Number of Participants With Adverse Events | No. of participants with SAEs | 1 Participants |
| Placebo | Number of Participants With Adverse Events | No. of participants discontinued due to AEs | 2 Participants |
| BMS-986165 3MG QOD | Number of Participants With Adverse Events | No. of participants with AEs | 26 Participants |
| BMS-986165 3MG QOD | Number of Participants With Adverse Events | No. of participants with SAEs | 1 Participants |
| BMS-986165 3MG QOD | Number of Participants With Adverse Events | No. of participants discontinued due to AEs | 1 Participants |
| BMS-986165 3MG QD | Number of Participants With Adverse Events | No. of participants with AEs | 25 Participants |
| BMS-986165 3MG QD | Number of Participants With Adverse Events | No. of participants with SAEs | 1 Participants |
| BMS-986165 3MG QD | Number of Participants With Adverse Events | No. of participants discontinued due to AEs | 2 Participants |
| BMS-986165 3MG BID | Number of Participants With Adverse Events | No. of participants with AEs | 29 Participants |
| BMS-986165 3MG BID | Number of Participants With Adverse Events | No. of participants with SAEs | 1 Participants |
| BMS-986165 3MG BID | Number of Participants With Adverse Events | No. of participants discontinued due to AEs | 1 Participants |
| BMS-986165 6MG BID | Number of Participants With Adverse Events | No. of participants with AEs | 36 Participants |
| BMS-986165 6MG BID | Number of Participants With Adverse Events | No. of participants with SAEs | 0 Participants |
| BMS-986165 6MG BID | Number of Participants With Adverse Events | No. of participants discontinued due to AEs | 3 Participants |
| BMS-986165 12MG QD | Number of Participants With Adverse Events | No. of participants with SAEs | 0 Participants |
| BMS-986165 12MG QD | Number of Participants With Adverse Events | No. of participants discontinued due to AEs | 1 Participants |
| BMS-986165 12MG QD | Number of Participants With Adverse Events | No. of participants with AEs | 34 Participants |
Primary
The Percentage of Participants With Moderate to Severe Psoriasis Experiencing a 75% Improvement (Reduction From Baseline) in PASI Score (PASI-75 Response Rate) on Day 85 (Week 12)
Psoriasis Area and Severity Index (PASI) 75 response: patients who achieved ≥ 75% improvement (reduction) in PASI score compared to baseline were defined as PASI 75 responders. PASI scores can range from 0, corresponding to no signs of psoriasis up to theoretical maximum of 72.0, which means a higher PASI score reflects a higher psoriasis activity.
Time frame: Day 1 to Day 85
Population: All Randomized and Treated Participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | The Percentage of Participants With Moderate to Severe Psoriasis Experiencing a 75% Improvement (Reduction From Baseline) in PASI Score (PASI-75 Response Rate) on Day 85 (Week 12) | 6.7 Percentage |
| BMS-986165 3MG QOD | The Percentage of Participants With Moderate to Severe Psoriasis Experiencing a 75% Improvement (Reduction From Baseline) in PASI Score (PASI-75 Response Rate) on Day 85 (Week 12) | 9.1 Percentage |
| BMS-986165 3MG QD | The Percentage of Participants With Moderate to Severe Psoriasis Experiencing a 75% Improvement (Reduction From Baseline) in PASI Score (PASI-75 Response Rate) on Day 85 (Week 12) | 38.6 Percentage |
| BMS-986165 3MG BID | The Percentage of Participants With Moderate to Severe Psoriasis Experiencing a 75% Improvement (Reduction From Baseline) in PASI Score (PASI-75 Response Rate) on Day 85 (Week 12) | 68.9 Percentage |
| BMS-986165 6MG BID | The Percentage of Participants With Moderate to Severe Psoriasis Experiencing a 75% Improvement (Reduction From Baseline) in PASI Score (PASI-75 Response Rate) on Day 85 (Week 12) | 66.7 Percentage |
| BMS-986165 12MG QD | The Percentage of Participants With Moderate to Severe Psoriasis Experiencing a 75% Improvement (Reduction From Baseline) in PASI Score (PASI-75 Response Rate) on Day 85 (Week 12) | 75.0 Percentage |
p-value: 0.4873Chi-squared
p-value: 0.0003Chi-squared
p-value: <0.0001Chi-squared
p-value: <0.0001Chi-squared
p-value: <0.0001Chi-squared
Secondary
Change From Baseline in BSA on Day 85
Measurement of psoriasis body surface area (BSA) involvement is estimated using the handprint method with the size of a patient's handprint representing \ 1% of body surface area involved.The total BSA = 100% with breakdown by body region as follows: head and neck = 10% (10 handprints), upper extremities = 20% (20 handprints), trunk including axillae and groin = 30% (30 handprints), lower extremities including buttocks = 40% (40 handprints). A decrease from Baseline indicates improvement. Change from Baseline was calculated as Baseline score - Day 85 score; a positive change from Baseline therefore indicates improvement.
Time frame: Day 1 to Day 85
Population: All Randomized and Treated Participants
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | Change From Baseline in BSA on Day 85 | -7.71 Percentage |
| BMS-986165 3MG QOD | Change From Baseline in BSA on Day 85 | -5.50 Percentage |
| BMS-986165 3MG QD | Change From Baseline in BSA on Day 85 | -12.59 Percentage |
| BMS-986165 3MG BID | Change From Baseline in BSA on Day 85 | -18.60 Percentage |
| BMS-986165 6MG BID | Change From Baseline in BSA on Day 85 | -17.23 Percentage |
| BMS-986165 12MG QD | Change From Baseline in BSA on Day 85 | -15.16 Percentage |
Secondary
Change From Baseline in DLQI Scores on Day 85
The DLQI is a participant reported quality of life index which consists of 10 questions concerning symptoms and feelings, daily activities, leisure, work, school, personal relationships, and treatment during the last week. Each question is scored on a scale of 0 to 3 by a tick box: not at all, a little, a lot, or very much. The scores are summed, giving a range from 0 (no impairment of life quality) to 30 (maximum impairment)
Time frame: Day 1 to Day 85
Population: All Randomized and Treated Participants
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | Change From Baseline in DLQI Scores on Day 85 | -2.85 Score |
| BMS-986165 3MG QOD | Change From Baseline in DLQI Scores on Day 85 | -3.76 Score |
| BMS-986165 3MG QD | Change From Baseline in DLQI Scores on Day 85 | -6.07 Score |
| BMS-986165 3MG BID | Change From Baseline in DLQI Scores on Day 85 | -9.67 Score |
| BMS-986165 6MG BID | Change From Baseline in DLQI Scores on Day 85 | -8.38 Score |
| BMS-986165 12MG QD | Change From Baseline in DLQI Scores on Day 85 | -10.16 Score |
Secondary
Percentage of Participants on Day 85 With PASI-50, PASI-90, PASI-100.
Percentage of patients achieving Psoriasis Area and Severity Index (PASI) 50, PASI 90 and PASI 100 responses on Day 85. PASI 50 response: patients who achieved ≥ 50% improvement (reduction) in PASI score compared to baseline were defined as PASI 50 responders. PASI 90 response: patients who achieved ≥ 90% improvement (reduction) in PASI score compared to baseline were defined as PASI 90 responders. PASI 100 response: patients who achieved ≥ 100% improvement (reduction) in PASI score compared to baseline were defined as PASI 100 responders. PASI scores can range from 0, corresponding to no signs of psoriasis up to theoretical maximum of 72.0, which means a higher PASI score reflects a higher psoriasis activity.
Time frame: Day 1 to Day 85
Population: All Randomized and Treated Participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants on Day 85 With PASI-50, PASI-90, PASI-100. | % of participants with PASI-90 at Day 85 | 2.2 Percentage |
| Placebo | Percentage of Participants on Day 85 With PASI-50, PASI-90, PASI-100. | % of participants with PASI-50 at Day 85 | 31.1 Percentage |
| Placebo | Percentage of Participants on Day 85 With PASI-50, PASI-90, PASI-100. | % of participants with PASI-100 at Day 85 | 0 Percentage |
| BMS-986165 3MG QOD | Percentage of Participants on Day 85 With PASI-50, PASI-90, PASI-100. | % of participants with PASI-90 at Day 85 | 6.8 Percentage |
| BMS-986165 3MG QOD | Percentage of Participants on Day 85 With PASI-50, PASI-90, PASI-100. | % of participants with PASI-50 at Day 85 | 43.2 Percentage |
| BMS-986165 3MG QOD | Percentage of Participants on Day 85 With PASI-50, PASI-90, PASI-100. | % of participants with PASI-100 at Day 85 | 2.3 Percentage |
| BMS-986165 3MG QD | Percentage of Participants on Day 85 With PASI-50, PASI-90, PASI-100. | % of participants with PASI-90 at Day 85 | 15.9 Percentage |
| BMS-986165 3MG QD | Percentage of Participants on Day 85 With PASI-50, PASI-90, PASI-100. | % of participants with PASI-50 at Day 85 | 68.2 Percentage |
| BMS-986165 3MG QD | Percentage of Participants on Day 85 With PASI-50, PASI-90, PASI-100. | % of participants with PASI-100 at Day 85 | 0 Percentage |
| BMS-986165 3MG BID | Percentage of Participants on Day 85 With PASI-50, PASI-90, PASI-100. | % of participants with PASI-90 at Day 85 | 44.4 Percentage |
| BMS-986165 3MG BID | Percentage of Participants on Day 85 With PASI-50, PASI-90, PASI-100. | % of participants with PASI-50 at Day 85 | 91.1 Percentage |
| BMS-986165 3MG BID | Percentage of Participants on Day 85 With PASI-50, PASI-90, PASI-100. | % of participants with PASI-100 at Day 85 | 8.9 Percentage |
| BMS-986165 6MG BID | Percentage of Participants on Day 85 With PASI-50, PASI-90, PASI-100. | % of participants with PASI-90 at Day 85 | 44.4 Percentage |
| BMS-986165 6MG BID | Percentage of Participants on Day 85 With PASI-50, PASI-90, PASI-100. | % of participants with PASI-50 at Day 85 | 77.8 Percentage |
| BMS-986165 6MG BID | Percentage of Participants on Day 85 With PASI-50, PASI-90, PASI-100. | % of participants with PASI-100 at Day 85 | 17.8 Percentage |
| BMS-986165 12MG QD | Percentage of Participants on Day 85 With PASI-50, PASI-90, PASI-100. | % of participants with PASI-50 at Day 85 | 88.6 Percentage |
| BMS-986165 12MG QD | Percentage of Participants on Day 85 With PASI-50, PASI-90, PASI-100. | % of participants with PASI-100 at Day 85 | 25.0 Percentage |
| BMS-986165 12MG QD | Percentage of Participants on Day 85 With PASI-50, PASI-90, PASI-100. | % of participants with PASI-90 at Day 85 | 43.2 Percentage |
Secondary
Percentage of Participants on Day 85 With sPGA Score of 0 or 1 (sPGA0/1 Response Rate).
Percentage of participants achieving a clear (0) or almost clear (1) status on the Static Physician Global Assessment (sPGA) on Day 85. This index evaluates the physician's global assessment of the participant's psoriasis based on severity of induration, scaling, and erythema. The assessment was scored on a scale of 0 to 5, where 0 = clear, with no evidence of plaque elevation, erythema, or scale, and 5 = severe induration, erythema, and scaling.
Time frame: Day 1 to Day 85
Population: All Randomized and Treated Participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants on Day 85 With sPGA Score of 0 or 1 (sPGA0/1 Response Rate). | 6.7 Percentage |
| BMS-986165 3MG QOD | Percentage of Participants on Day 85 With sPGA Score of 0 or 1 (sPGA0/1 Response Rate). | 20.5 Percentage |
| BMS-986165 3MG QD | Percentage of Participants on Day 85 With sPGA Score of 0 or 1 (sPGA0/1 Response Rate). | 38.6 Percentage |
| BMS-986165 3MG BID | Percentage of Participants on Day 85 With sPGA Score of 0 or 1 (sPGA0/1 Response Rate). | 75.6 Percentage |
| BMS-986165 6MG BID | Percentage of Participants on Day 85 With sPGA Score of 0 or 1 (sPGA0/1 Response Rate). | 64.4 Percentage |
| BMS-986165 12MG QD | Percentage of Participants on Day 85 With sPGA Score of 0 or 1 (sPGA0/1 Response Rate). | 75.0 Percentage |
Secondary
Trough Observed Plasma Concentration of BMS-986165 (Ctrough)
Pharmacokinetics of BMS-986165 were derived from plasma concentration versus time data. Ctrough= Trough observed plasma concentration
Time frame: Days 8, 15, 29, 57, 85
Population: All participants who received any study medication and have any available concentration-time data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Trough Observed Plasma Concentration of BMS-986165 (Ctrough) | 2.024 ng/mL | Standard Deviation 3.7061 |
| BMS-986165 3MG QOD | Trough Observed Plasma Concentration of BMS-986165 (Ctrough) | 3.145 ng/mL | Standard Deviation 3.1588 |
| BMS-986165 3MG QD | Trough Observed Plasma Concentration of BMS-986165 (Ctrough) | 14.819 ng/mL | Standard Deviation 9.141 |
| BMS-986165 3MG BID | Trough Observed Plasma Concentration of BMS-986165 (Ctrough) | 26.257 ng/mL | Standard Deviation 14.6483 |
| BMS-986165 6MG BID | Trough Observed Plasma Concentration of BMS-986165 (Ctrough) | 17.824 ng/mL | Standard Deviation 22.7536 |