Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
BMS-986165 · 33 trials · 18 indications
static Physician Global Assessment (sPGA) 0 or 1 response assessed as a percentage of participants with a sPGA score of 0 or 1 as assessed at week 16 with at least a 2-point improvement from baseline. The sPGA is a 5-point scale of an average assessment of all psoriatic lesions based on erythema, scale, and induration. The sPGA measure determines psoriasis severity at a single point in time (without taking into account the baseline disease condition) as clear (0), almost clear (1), mild (2), moderate (3), or severe (4). A higher score equates to higher severity of disease. The individual scores at each visit will range from 0-4 and will be captured for erythema, induration, and scaling. A total score will also be computed based on the average of the 3 characteristic scores. The average score will be rounded to the nearest whole number and data for this endpoint will be derived from the total average score.
Psoriasis Area and Severity Index (PASI) 75 response is an assessment defined as the percentage of participants who experience at least a 75% improvement in PASI score at Week 16 as compared with baseline value. PASI is a measure of the average redness, thickness, and scaliness of psoriatic skin lesions graded on a scale from 0-4 (0= absent symptoms, 1= mild symptoms, 2= moderate symptoms, 3= severe symptoms, 4= very severe symptoms), weighted by the area of involvement (head, arms, trunk to groin, and legs to top of buttocks). The PASI produces a numeric score that can range from 0 to 72, with higher PASI scores denoting more severe disease activity. The PASI includes multiple subscores and a final total score. Individual plaque characteristic rating scores are provided for each body region as well as the weighted score. The PASI Total score will be used to assess response to treatment.
Vaccine cohort only Defined as ≥ 2-fold increase in immunoglobulin (IgG) antibody titers or geometric mean fold rise (GMFRs) titers of ≥ 6
Vaccine cohort only A serologic response is defined as: * Postvaccination titer levels ≥ 0.40 IU/mL if prevaccination IgG antibody titer level is ≤ 0.10 IU/mL OR * Postvaccination titer levels of at least a 4-fold increase if prevaccination titer level is \> 0.10 IU/mL and ≤ 2.7 IU/mL OR * Postvaccination titer levels of at least a 2-fold increase if prevaccination titer level is \> 2.7 IU/mL
The sPGA is a 5-point scale of an average assessment of all psoriatic lesions based on erythema, scale, and induration. sPGA 0/1 is the response as a number of participants who experience a sPGA score that determines psoriasis severity as clear (0) or almost clear (1) with at least 2-point improvement from baseline at week 16 using the non-responder imputation (NRI) method. The higher sPGA score denotes to more severe disease activity: * Clear (0) * Almost clear (1) * Mild (2) * Moderate (3) * Severe (4)
PASI is a measure of the average redness, thickness, and scaliness of psoriatic skin lesions (each graded on a 0 to 4 scale; 0 = none to 4 = very severe), weighted by the area of involvement (head, upper extremities, trunk, and lower extremities). The PASI produces a numeric score that can range from 0 to 72, with higher PASI scores denoting more severe disease activity. PASI 75 is the response as a number of participants who experience at least a 75% improvement in PASI score as compared with the baseline value using the non-responder imputation (NRI) method.
The sPGA is a 5-point scale of an average assessment of all psoriatic lesions based on erythema, scale, and induration. The average of the 3 scales, which is rounded to the nearest whole number, is the final sPGA score. The higher sPGA score denotes to more severe disease activity (0 = Clear; 1 = Almost clear; 2 = Mild; 3 = Moderate; Severe = 4). sPGA 0/1 is the response as a number of participants who experience a sPGA score that determines psoriasis severity as 0 or 1 with at least 2-point improvement from baseline using the non-responder imputation (NRI) method that will be used for participants who discontinue treatment or study prior to week 16 or who have missing week 16 endpoint data for any reason.
PASI is a measure of the average redness, thickness, and scaliness of psoriatic skin lesions (each graded on a 0 to 4 scale; 0 = none to 4 = very severe), weighted by the area of involvement (head, upper extremities, trunk, and lower extremities). The PASI produces a numeric score that can range from 0 to 72, with higher PASI scores denoting more severe disease activity. PASI 75 is the response as a number of participants who experience at least a 75% improvement in PASI score as compared with the baseline value using the non-responder imputation (NRI) method that will be used for participants who discontinue treatment or study prior to week 16 or who have missing week 16 endpoint data for any reason. Baseline is defined as the measurement at the randomization visit (Week 0).
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)
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.
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.
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.
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.
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
A Treatment-Emergent Adverse Event (TEAE) is any untoward medical occurrence that begins or worsens after the first dose of study treatment, including any unfavorable sign, symptom, disease, or abnormal lab finding, whether or not related to the product, and may include worsening of pre-existing conditions. A Serious Adverse Event (SAE) is any untoward medical occurrence that results in death, is life-threatening, requires or prolongs hospitalization, causes persistent or significant disability/incapacity, leads to a congenital anomaly/birth defect, or is considered an important medical event requiring intervention to prevent these outcomes.
Vital signs heart rate (HR) (beats/min), systolic blood pressure (SBP) (mmHG), and diastolic blood pressure (DBP) (mmHg).
Blood samples were collected to assess laboratory parameters. Grade 3 = Severe laboratory abnormality Grade 4 = Life-threatening or very severe laboratory abnormality
SRI(4) responder is defined as a patient whose disease course fulfills all of the following: 1. A 4-point or greater reduction from baseline in SLEDAI-2K score 2. No new British Isles Lupus Assessment Group (BILAG) A (severe disease activity) and not more than 1 new BILAG B (moderate disease activity) organ domain grade 3. No worsening from baseline in the Physician's Global Assessment of Disease Activity Scale by more than 0.3 points on a 3-point visual analog scale from no disease activity to severe disease activity
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.
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
Measured by plasma concentration.
Measured by plasma concentration.
Measured by plasma concentration.
Adverse Event (AE), Serious adverse event (SAE)
| Arm | Type | Description |
|---|---|---|
| Arm A:BMS-986165 oral administration | EXPERIMENTAL | - |
| Arm B: Placebo oral administration | PLACEBO_COMPARATOR | - |
| BMS-986165 | EXPERIMENTAL | - |
| Vaccine Cohort | EXPERIMENTAL | - |
| Placebo | PLACEBO_COMPARATOR | - |
| Apremilast | ACTIVE_COMPARATOR | - |
| Active comparator | ACTIVE_COMPARATOR | Active comparator oral administration |
| Open label Extension, BMS-986165 | EXPERIMENTAL | - |
| BMS-986165 Dose 1 | EXPERIMENTAL | - |
| BMS-986165 Dose 2 | EXPERIMENTAL | - |
| BMS-986165 Dose 3 | EXPERIMENTAL | - |
| BMS-986165 Dose 1 oral administration | EXPERIMENTAL | - |
| BMS-986165 Dose 2 oral administration | EXPERIMENTAL | - |
| BMS-986165 Dose 3 oral administration | EXPERIMENTAL | - |
| Placebo oral administration | PLACEBO_COMPARATOR | - |
| BMS-986165 Dose 4 | EXPERIMENTAL | Specified dose of BMS-986165 on specified days. |
| BMS-986165 Dose 5 | EXPERIMENTAL | Specified dose of BMS-986165 on specified days. |
| Arm 1: BMS-986165 Dose 1 + Metformin | EXPERIMENTAL | - |
| Arm 2: BMS-986165 Dose 2 + Metformin | EXPERIMENTAL | - |
| Treatment A : BMS-986165 | EXPERIMENTAL | - |
| Treatment B: BMS-986165 prototype 1 | EXPERIMENTAL | - |
| Treatment C: BMS-986165 prototype 2 | EXPERIMENTAL | - |
| Treatment D: BMS-986165 prototype 2 | EXPERIMENTAL | - |
| Treatment A: BMS-986165 alone, fasted | EXPERIMENTAL | - |
| Treatment B: BMS-986165 alone, fed | EXPERIMENTAL | - |
| Treatment C: BMS-986165 with famotidine pretreatment, fasted | EXPERIMENTAL | - |
| Arm A: Single Dose (BMS-986165) | EXPERIMENTAL | - |
| Arm B:Diflunisal and Single Dose (BMS-986165) | EXPERIMENTAL | - |
| BMS- 986185 + Pyrimethamine | EXPERIMENTAL | - |
| BMS-986185 | EXPERIMENTAL | - |
| Combination Therapy | EXPERIMENTAL | - |
| BMS-986165 + Rabeprazole | EXPERIMENTAL | - |
| BMS-986165+Fluvoxamine | EXPERIMENTAL | - |
| BMS-986165 only | EXPERIMENTAL | - |
| Fluvoxamine only | EXPERIMENTAL | - |
| Normal renal function | EXPERIMENTAL | Single dose |
| Mild renal disease | EXPERIMENTAL | Single dose |
| Moderate renal failure | EXPERIMENTAL | Single dose |
| Severe renal failure | EXPERIMENTAL | Single dose |
| End-stage renal disease requiring dialysis | EXPERIMENTAL | Two single doses administered with washout |
| Group 1: BMS-986165 Dose 1 | EXPERIMENTAL | Participants will receive Dose 1 on Day 1, and from Day 5 - 19. |
| Group 2: BMS-986165 Dose 2 | EXPERIMENTAL | Participants will receive Dose 2 on Day 1, and from Day 5 - 19. |
| Group 1: Placebo Dose 1 | PLACEBO_COMPARATOR | Participants will receive placebo matching Dose 1 on Day 1, and from Day 5 - 19. |
| Group 2: Placebo Dose 2 | PLACEBO_COMPARATOR | Participants will receive placebo matching Dose 2 on Day 1, and from Day 5 - 19. |
| Normal liver function | EXPERIMENTAL | Single dose |
| Mild liver impairment | EXPERIMENTAL | Single dose |
| Moderate liver impairment | EXPERIMENTAL | Single dose |
| Severe liver impairment | EXPERIMENTAL | Single dose |
| Formulation A | EXPERIMENTAL | Dosage formulation and area of release varies between arms |
| Formulation B | EXPERIMENTAL | Dosage formulation and area of release varies between arms |
| Formulation C | EXPERIMENTAL | Dosage formulation and area of release varies between arms |
| Formulation D | EXPERIMENTAL | Dosage formulation and area of release varies between arms |
| Formulation E | EXPERIMENTAL | Dosage formulation and area of release varies between arms |
| Formulation F | EXPERIMENTAL | Dosage formulation and area of release varies between arms |
| Formulation G | EXPERIMENTAL | Dosage formulation and area of release varies between arms |
| Formulation H | EXPERIMENTAL | Dosage formulation and area of release varies between arms |
| BMS-986165 taste evaluation | EXPERIMENTAL | BMS-986165 taste evaluation using Active Pharmaceutical Ingredient (API) and Prototypes of the API containing various flavors and sweeteners |
| BMS-986165 + MMF | EXPERIMENTAL | Oral administration |
| Moxifloxacin Dose 3 oral administration | ACTIVE_COMPARATOR | Moxifloxacin positive control single dose |
| Placebo Dose 4 oral administration | PLACEBO_COMPARATOR | Placebo single dose |
| BMS-986165 and cyclosporine | EXPERIMENTAL | BMS-986165 and cyclosporine administered orally |
| BMS-986165+Methotrexate+Leucovorin | EXPERIMENTAL | Three treatments administered |
| Tablet-Capsule Crossover 1 | EXPERIMENTAL | Variations between arms dependent on timing, fasting, dose and receiving the tablet or capsule at different treatment period combinations |
| Tablet-Capsule Crossover 2 | EXPERIMENTAL | Variations between arms dependent on timing, fasting, dose and receiving the tablet or capsule at different treatment period combinations |
| Tablet-Capsule Crossover 3 | EXPERIMENTAL | Variations between arms dependent on timing, fasting, dose and receiving the tablet or capsule at different treatment period combinations |
| Tablet-Capsule Crossover 4 | EXPERIMENTAL | Variations between arms dependent on timing, fasting, dose and receiving the tablet or capsule at different treatment period combinations |
| Tablet-Capsule Crossover 5 | EXPERIMENTAL | Variations between arms dependent on timing, fasting, dose and receiving the tablet or capsule at different treatment period combinations |
| Tablet-Capsule Crossover 6 | EXPERIMENTAL | Variations between arms dependent on timing, fasting, dose and receiving the tablet or capsule at different treatment period combinations |
| BMS-986165 and Oral Contraceptive | EXPERIMENTAL | Oral administration of contraceptive, then progress to combination |
| BMS 986165 and Rosuvastatin | EXPERIMENTAL | - |
| Single dose of radiolabeled BMS-986165 | EXPERIMENTAL | - |
| Part A: Single ascending dose | EXPERIMENTAL | BMS-986165 or Placebo specified dose on specified days |
| Part B: Multiple ascending dose | EXPERIMENTAL | BMS-986165 or Placebo + Interferon alpha-2a recombinant specified dose on specified days |
| Part C: Multiple ascending dose | EXPERIMENTAL | BMS-986165 or Placebo specified dose on specified days |
| Part D: Relative Bioavailability | EXPERIMENTAL | BMS-986165 (Liquid) + BMS-986165 (Capsule) + Famotidine specified dose on specified days |
| Name | Type | Description |
|---|---|---|
| BMS-986165 | DRUG | Specified dose on Specified Days |
| Placebo | OTHER | Specified dose on Specified days |
| Apremilast | DRUG | Specified dose on specified days |
| Placebo Comparator | OTHER | Specified Dose on Specified Days |
| Placebo for BMS-986165 | DRUG | - |
| Metformin | DRUG | Specified dose on specified days |
| BMS-986165 prototype 1 | DRUG | Specified dose on specified days |
| BMS-986165 prototype 2 | DRUG | Specified dose on specified days |
| Famotidine | DRUG | Single dose |
| diflunisal | DRUG | Specified Dose on Specified Days |
| Pyrimethamine | DRUG | Oral administration of Pyrimethamine in combination with BMS-986185 |
| Ritonavir | DRUG | 100 mg |
| Rabeprazole | DRUG | Specified dose on specified days. |
| Fluvoxamine | DRUG | Participants will receive fluvoxamine. |
| Active Pharmaceutical Ingredient | DRUG | Swish and expectorate after tasting |
| MMF | DRUG | Specified dose on specified days |
| Moxifloxacin | DRUG | Specified dose on specified days |
| Cyclosporine | DRUG | Specified dose on specified days |
| Methotrexate | DRUG | Specified dose on specified days |
| Leucovorin | DRUG | Specified dose on specified days |
| BMS-986165 Capsule | DRUG | Oral capsule |
| BMS-986165 Tablet | DRUG | Oral tablet |
| Loestrin 1.5/30 (1.5 mg norethindrone acetate/30 μg ethinyl estradiol) | DRUG | Oral Contraceptive |
| Rosuvastatin | DRUG | Rosuvastatin on Day 1. BMS 986165 on Days 5-8 and Days 10-12. On Day 9, BMS 986165 coadministered with an oral dose of rosuvastatin. |
| Interferon alpha-2a recombinant | DRUG | - |
Inclusion Criteria: * Plaque psoriasis for at least 6 months * Moderate to severe disease * Candidate for phototherapy or systemic therapy Exclusion Criteria: * Other forms of psoriasis * History of recent infection * Prior exposure to BMS-986165 Other inclusion/exclusion criteria may apply.