NCT03329885

A Study of Experimental Medication BMS-986251, Taken by Mouth, in Healthy Participants and Patients With Average to Very Serious Psoriasis

Terminated Phase 1, PHASE2 Results posted Last updated 21 October 2019

What this trial tests

Phase 1, PHASE2 trial testing BMS-986251 in Rheumatoid Arthritis in 38 participants. Terminated before completion.

Timeline

2 November 2017

Primary endpoint
26 June 2018

26 June 2018

Quick facts

Lead sponsor	Bristol-Myers Squibb
Phase	Phase 1, PHASE2
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	38
Start date	2 November 2017
Primary completion	26 June 2018
Estimated completion	26 June 2018
Sites	1 location across Netherlands

Drugs / interventions tested

• BMS-986251 — full drug profile →
• Placebo

Conditions studied

• Rheumatoid Arthritis — all drugs for Rheumatoid Arthritis →
• Psoriasis — all drugs for Psoriasis →
• Ankylosing Spondylitis — all drugs for Ankylosing Spondylitis →
• Inflammatory Bowel Diseases — all drugs for Inflammatory Bowel Diseases →

Sponsor

Bristol-Myers Squibb — full company profile →

Who can join

Adults 18 to 70, any sex, with Rheumatoid Arthritis or Psoriasis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants That Experienced the Following: Serious Adverse Events (SAEs), Death or an Adverse Event (AE) Leading to Study Discontinuation Primary · AEs: Day 1 to Day 11 (Part A), Day 1 to Day 24 (Part B); SAEs: Day -21 to within 30 days of discontinuation of dosing (Part A), Day -21 to within 30 days of discontinuation of dosing (Part B)

An adverse event (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 the treatment. A Serious Adverse Event is defined as any untoward medical occurrence that, at any dose results in death or is life-threatening or requires inpatient hospitalization

% of participants that experienced SAEs

Group	Value	95% CI
Part A: Placebo	0
Part A: BMS-986251 2 mg	0
Part A: BMS-986251 6 mg	0
Part A: BMS-986251 15 mg	0
Part A: BMS-986251 30 mg	0
Part A : BMS-986251 60 mg	0
Part B: Placebo	0
Part B: 3 mg QD (Once Daily)	0

% of participants that died

Group	Value	95% CI
Part A: Placebo	0
Part A: BMS-986251 2 mg	0
Part A: BMS-986251 6 mg	0
Part A: BMS-986251 15 mg	0
Part A: BMS-986251 30 mg	0
Part A : BMS-986251 60 mg	0
Part B: Placebo	0
Part B: 3 mg QD (Once Daily)	0

% of participants with AE leading to study discon.

Group	Value	95% CI
Part A: Placebo	0
Part A: BMS-986251 2 mg	0
Part A: BMS-986251 6 mg	0
Part A: BMS-986251 15 mg	0
Part A: BMS-986251 30 mg	0
Part A : BMS-986251 60 mg	0
Part B: Placebo	0
Part B: 3 mg QD (Once Daily)	0

Number of Participants With Potentially Clinically Significant Changes in Vital Signs Primary · Part A: Days 1, 2, 3, 4, 5, 6, 7, 9 and 11; Part B: Days 1, 2-13, 15, 16, 18, 20, 24

Vital signs (Systolic and diastolic blood pressure and pulse) were recorded after the participant had been resting for at least 5 minutes in the supine position.

Group	Value	95% CI
Part A: Placebo	0
Part A: BMS-986251 2 mg	0
Part A: BMS-986251 6 mg	0
Part A: BMS-986251 15 mg	0
Part A: BMS-986251 30 mg	0
Part A : BMS-986251 60 mg	0
Part B: Placebo	0
Part B: 3 mg QD (Once Daily)	0

Number of Participants With Potentially Clinically Significant Changes in Electrocardiogram (ECG) Parameters Primary · Part A: Days 1, 2, 3,5, 7 and 11; Part B: Days 1, 2, 4, 6, 8, 10, and 12,24

The following ECG parameters were recorded: heart rate, PR-interval, QRS-duration, QT-interval, QTcinterval, (Fridericia's) and the interpretation of the ECG profile by the Investigator

Group	Value	95% CI
Part A: Placebo	0
Part A: BMS-986251 2 mg	0
Part A: BMS-986251 6 mg	0
Part A: BMS-986251 15 mg	0
Part A: BMS-986251 30 mg	0
Part A : BMS-986251 60 mg	0
Part B: Placebo	0
Part B: 3 mg QD (Once Daily)	0

Number of Participants With Potentially Clinically Significant Changes in Clinical Laboratory Parameters Primary · Part A: Days 2, 4, 7 and 11; Part B: Days 3, 7, 10, 14, 16, 24

Hematology: Hemoglobin, Hematocrit, Total leukocyte count, including differential Platelet count, Red blood cell count, Reticulocyte count; Chemistry: Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Total bilirubin, Direct bilirubin, Alkaline phosphatase, Lactate dehydrogenase , (LDH), Creatinine, Urea, Uric acid, Fasting glucose, High sensitivity C-reactive protein (hs-CRP), Total protein, Albumin Sodium, Potassium, Chloride, Calcium Inorganic phosphate, Magnesium, Creatine kinase, Creatinine clearance (CLcr)- screening only, Cholesterol Triglycerides, High-density lipoprot

Group	Value	95% CI
Part A: Placebo	0
Part A: BMS-986251 2 mg	0
Part A: BMS-986251 6 mg	0
Part A: BMS-986251 15 mg	0
Part A: BMS-986251 30 mg	0
Part A : BMS-986251 60 mg	0
Part B: Placebo	0
Part B: 3 mg QD (Once Daily)	0

Maximum Observed Plasma Concentration (Cmax) Primary · Part A: Days 1, 2, 3, 4, 5, 6, 7, 9, 11; Part B : Day 1 and 14

PK parameters were derived from BMS-986251 concentration versus time data measured at the time points specified

Group	Value	95% CI
Part A: BMS-986251 2 mg	74.3	± 5.88
Part A: BMS-986251 6 mg	206	± 55.8
Part A: BMS-986251 15 mg	659	± 207
Part A: BMS-986251 30 mg	1131	± 278
Part A : BMS-986251 60 mg	2147	± 175
Part B: 3 mg QD (Once Daily)	NA	± NA

Time of Maximum Observed Plasma Concentration (Tmax) Primary · Part A: Days 1, 2, 3, 4, 5, 6, 7, 9, 11; Part B : Day 1 and 14

PK parameters were derived from BMS-986251 concentration versus time data measured at the time points specified

Group	Value	95% CI
Part A: BMS-986251 2 mg	3.50	1.50 – 6.00
Part A: BMS-986251 6 mg	2.27	1.02 – 4.02
Part A: BMS-986251 15 mg	1.53	1.02 – 8.00
Part A: BMS-986251 30 mg	2.53	2.02 – 4.02
Part A : BMS-986251 60 mg	1.05	1.02 – 1.07
Part B: 3 mg QD (Once Daily)	NA	NA – NA

Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration [AUC(0-t)] Primary · Part A: Days 1, 2, 3, 4, 5, 6, 7, 9, 11; Part B : Day 1 and 14

PK parameters were derived from BMS-986251 concentration versus time data measured at the time points specified

Group	Value	95% CI
Part A: BMS-986251 2 mg	5530	± 954
Part A: BMS-986251 6 mg	14737	± 3339
Part A: BMS-986251 15 mg	36318	± 9554
Part A: BMS-986251 30 mg	71172	± 13328
Part A : BMS-986251 60 mg	126198	± 21811
Part B: 3 mg QD (Once Daily)	NA	± NA

Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinite Time [AUC(0-inf)] (Part A) Primary · Part A: Days 1, 2, 3, 4, 5, 6, 7, 9, 11

PK parameters were derived from BMS-986251 concentration versus time data measured at the time points specified

Group	Value	95% CI
Part A: BMS-986251 2 mg	6052	± 1221
Part A: BMS-986251 6 mg	15815	± 3926
Part A: BMS-986251 15 mg	38080	± 10827
Part A: BMS-986251 30 mg	75335	± 14726
Part A : BMS-986251 60 mg	130873	± 24294

Terminal Elimination Half-life, Calculated as 0.693/Kel [t(1/2)] Primary · Part A: Days 1, 2, 3, 4, 5, 6, 7, 9, 11; Part B : Day 14

PK parameters were derived from BMS-986251 concentration versus time data measured at the time points specified

Group	Value	95% CI
Part A: BMS-986251 2 mg	70.9	± 16.5
Part A: BMS-986251 6 mg	62.6	± 15.0
Part A: BMS-986251 15 mg	52.2	± 9.02
Part A: BMS-986251 30 mg	54.6	± 13.6
Part A : BMS-986251 60 mg	48.2	± 7.02
Part B: 3 mg QD (Once Daily)	NA	± NA

Apparent (Oral) Clearance (CL/F) Calculated as Dose/[AUC(0-inf)] for Single Dose Primary · Part A: Day 1, Part B: Day 14

PK parameters were derived from BMS-986251 concentration versus time data measured at the time points specified

Group	Value	95% CI
Part A: BMS-986251 2 mg	0.343	± 0.076
Part A: BMS-986251 6 mg	0.400	± 0.100
Part A: BMS-986251 15 mg	0.419	± 0.109
Part A: BMS-986251 30 mg	0.411	± 0.078
Part A : BMS-986251 60 mg	0.469	± 0.083
Part B: 3 mg QD (Once Daily)	NA	± NA

Apparent Volume of Distribution at Terminal Phase [V(z)/F] Primary · Part A: Days 1, 2, 3, 4, 5, 6, 7, 9, 11; Part B : Day 14

PK parameters were derived from BMS-986251 concentration versus time data measured at the time points specified

Group	Value	95% CI
Part A: BMS-986251 2 mg	34.1	± 6.39
Part A: BMS-986251 6 mg	35.3	± 8.52
Part A: BMS-986251 15 mg	30.6	± 5.54
Part A: BMS-986251 30 mg	32.3	± 9.44
Part A : BMS-986251 60 mg	32.1	± 3.98
Part B: 3 mg QD (Once Daily)	NA	± NA

Cumulative Urinary Excretion (of the Unchanged Drug) [Ae(t)] Primary · Part A: Days 1, 2, 3, 4, 5, 6, 7 ; Part B : Day 14

Summary of BMS-986251 Excretion Parameters in Urine. PK parameters were derived from BMS-986251 concentration versus time data measured at the time points specified

Group	Value	95% CI
Part A: BMS-986251 2 mg	0	± 0
Part A: BMS-986251 6 mg	0	± 0
Part A: BMS-986251 15 mg	0.002	± 0.002
Part A: BMS-986251 30 mg	0.009	± 0.002
Part A : BMS-986251 60 mg	0.020	± 0.011
Part B: 3 mg QD (Once Daily)	NA	± NA

Adverse events — posted to ClinicalTrials.gov

Time frame: AEs: Day 1 to Day 11 (Part A), Day 1 to Day 24 (Part B); SAEs: Day -21 to within 30 days of discontinuation of dosing (Part A), Day -21 to within 30 days of discontinuation of dosing (Part B) (Approximately 9 months). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Part A: Placebo

Serious: 0/9 (0%)

Deaths: 0/9

Part A: BMS-986251 2 mg

Serious: 0/6 (0%)

Deaths: 0/6

Part A: BMS-986251 6 mg

Serious: 0/6 (0%)

Deaths: 0/6

Part A: BMS-986251 15 mg

Serious: 0/6 (0%)

Deaths: 0/6

Part A: BMS-986251 30 mg

Serious: 0/6 (0%)

Deaths: 0/6

Part A : BMS-986251 60 mg

Serious: 0/3 (0%)

Deaths: 0/3

Part B: Placebo

Serious: 0/1 (0%)

Deaths: 0/1

Part B: 3 mg QD (Once Daily)

Serious: 0/1 (0%)

Deaths: 0/1

Other adverse events (29 terms — click to expand)

Reaction	System	Part A: Placebo	Part A: BMS-986251 2 mg	Part A: BMS-986251 6 mg	Part A: BMS-986251 15 mg	Part A: BMS-986251 30 mg	Part A : BMS-986251 60 mg	Part B: Placebo	Part B: 3 mg QD (Once Daily)
Headache	Nervous system disorders	—	—	—	—	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—	—	—	—	—
Dry Mouth	Gastrointestinal disorders	—	—	—	—	—	—	—	—
Fatigue	General disorders	—	—	—	—	—	—	—	—
Nasopharyngitis	Infections and infestations	—	—	—	—	—	—	—	—
Abdominal Discomfort	Gastrointestinal disorders	—	—	—	—	—	—	—	—
Abdominal Distension	Gastrointestinal disorders	—	—	—	—	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—	—	—	—	—
Flatulence	Gastrointestinal disorders	—	—	—	—	—	—	—	—
Food Poisoning	Gastrointestinal disorders	—	—	—	—	—	—	—	—
Haematochezia	Gastrointestinal disorders	—	—	—	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—	—	—	—
Proctalgia	Gastrointestinal disorders	—	—	—	—	—	—	—	—
Vessel Puncture Site Reaction	General disorders	—	—	—	—	—	—	—	—
Catheter Site Haematoma	General disorders	—	—	—	—	—	—	—	—
Catheter Site Related Reaction	General disorders	—	—	—	—	—	—	—	—
Complication Associated With Device	General disorders	—	—	—	—	—	—	—	—
Medical Device Site Reaction	General disorders	—	—	—	—	—	—	—	—
Back Pain	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—
Musculoskeletal Chest Pain	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—
Musculoskeletal Stiffness	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—	—	—	—	—
Poor Quality Sleep	Nervous system disorders	—	—	—	—	—	—	—	—
Anxiety	Psychiatric disorders	—	—	—	—	—	—	—	—
Dysmenorrhoea	Reproductive system and breast disorders	—	—	—	—	—	—	—	—
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—
Acne	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—	—
Blister	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—	—
Dry Skin	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—	—

Data from ClinicalTrials.gov NCT03329885 adverse events section.

Sponsor's own description

The purpose of this study is to investigate experimental medication BMS-986251 taken by mouth in healthy patients and patients with average to very serious Psoriasis (a condition characterized by itchy, dry skin with a scaly rash).

Publications & conference data

4 peer-reviewed publications reference this trial (live from Europe PMC):

1. Major Role of the IL17/23 Axis in Psoriasis Supports the Development of New Targeted Therapies.
   Bugaut H, Aractingi S. · · 2021 · cited 81× · PMID 33717124 · DOI 10.3389/fimmu.2021.621956
2. Discovery of BMS-986251: A Clinically Viable, Potent, and Selective RORγt Inverse Agonist.
   Cherney RJ, Cornelius LAM, Srivastava A, Weigelt CA, et al · · 2020 · cited 32× · PMID 32551004 · DOI 10.1021/acsmedchemlett.0c00063
3. New and Emerging Oral/Topical Small-Molecule Treatments for Psoriasis.
   Carmona-Rocha E, Rusiñol L, Puig L. · · 2024 · cited 28× · PMID 38399292 · DOI 10.3390/pharmaceutics16020239
4. The 2023 pipeline of disease-modifying antirheumatic drugs (DMARDs) in clinical development for spondyloarthritis (including psoriatic arthritis): a systematic review of trials.
   Denis A, Sztejkowski C, Arnaud L, Becker G, et al · · 2023 · cited 17× · PMID 37507210 · DOI 10.1136/rmdopen-2023-003279