Rheumatoid ArthritisPhase 1/2NCT03329885

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

A Phase 1/2 study testing BMS-986251 in people with Rheumatoid Arthritis and Psoriasis, run by Bristol-Myers Squibb at 1 site in Netherlands.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

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). Read more about this study

Who is it for?: Ages 18 to 70 yearsHealthy volunteers can take part
Conditions the study is for: Rheumatoid Arthritis, Psoriasis, Ankylosing Spondylitis
What is being tested?: BMS-986251
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 38 participants
Where: 1 siteNetherlands
Study dates: 2 Nov 2017to 26 Jun 2018
Phase: Phase 1/2

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 70 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

Males and females, ages 18 to 55 years, inclusive, at screening
Healthy subjects, as determined by no clinically significant deviations from normal in medical history, physical examination, 12-lead ECGs, vital signs, and clinical laboratory results
Body mass index (BMI) of 18.0 to 30.0 kg/m2, inclusive, at screening
Body weight between 55 kg and 105 kg, inclusive, at screening
Women must not be breastfeeding
Males and females, ages 18 to 70 years, inclusive, at screening

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BMI of 18.0 to 35.0 kg/m2, inclusive, at screening
Body weight between 55 kg and 120 kg, inclusive, at screening
Diagnosed with stable chronic plaque psoriasis, for at least 6 months prior to screening and be candidates for either photo-therapy or systemic treatment
Moderate-to-severe intensity of psoriasis as defined by:
Affected body surface area (BSA) of ≥10%
Psoriasis Area and Severity Index (PASI) ≥12
Physician Global Assessment (PGA; 6-point scale) ≥3

Who cannot join

Previous participation in the current study
Participation in a drug study or exposure to any investigational drug or placebo within 2 months prior to (the first) drug administration in the current study
Employees of PRA or the Sponsor and their relatives
Any significant acute or chronic medical condition that presents a potential risk to the subject and/or that may compromise the objectives of the study, including active, or history of, liver disease, or intestinal disorder including irritable bowel syndrome
Current or recent (within 3 months of study treatment administration) gastrointestinal disease that could affect pharmacokinetics; history of cholecystectomy is not allowed
Previous participation in the current study

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Participation in a drug study or exposure to any investigational drug or placebo within 2 months prior to (the first) drug administration in the current study
Employees of PRA or the Sponsor and their relatives
Any significant acute or chronic medical condition that presents a potential risk to the subject and/or that may compromise the objectives of the study, including active, or history of, liver disease, or intestinal disorder including irritable bowel syndrome
Current or recent (within 3 months of study treatment administration) gastrointestinal disease that could affect pharmacokinetics; history of cholecystectomy is not allowed
Other protocol defined inclusion/exclusion criteria could apply

Trial locations and contacts

1 site in 1 country.

Netherlands1 site

Local Institution
Groningen, 9728 NZ

Other trials in Netherlands

About this study

Official title: A Double-Blind Randomized Placebo-Controlled Single and Multiple Ascending Doses Study of the Safety and Tolerability, Pharmacokinetics (Including Bioavailability Comparison and Food Effect) and Pharmacodynamics of Oral BMS-986251 Administration in Healthy Subjects, With Efficacy Assessment of Multiple Doses in Patients With Moderate-to-Severe Psoriasis

Conditions: Rheumatoid Arthritis, Psoriasis, Ankylosing Spondylitis, Inflammatory Bowel Diseases, Nonalcoholic Steatohepatitis
Being tested: BMS-986251, Placebo
Medical subject headings: Arthritis, Rheumatoid, Psoriasis, Spondylitis, Ankylosing, Inflammatory Bowel Diseases, Non-alcoholic Fatty Liver Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

BMS-986251Drug
Escalating oral dose
PlaceboOther
Escalating oral dose

Study groups in NCT03329885
Study group	Role	What they receive
Part A Single Ascending Dose (SAD) in Healthy Patients	Experimental	Healthy patient will receive single escalating oral doses of BMS-986251 or placebo Receives: Drug: BMS-986251; Other: Placebo
Part B Multiple Ascending Dose (MAD) in Healthy Patients	Experimental	Healthy patients will receive daily escalating oral doses of BMS-986251 or placebo Receives: Drug: BMS-986251; Other: Placebo
Part C Multiple Dosing in Psoriasis Patients	Experimental	Psoriasis patients will receive daily escalating oral doses of BMS-986251 or placebo Receives: Drug: BMS-986251; Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Participants That Experienced the Following: Serious Adverse Events (SAEs), Death or an Adverse Event (AE) Leading to Study Discontinuation
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
Measured: 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)
Number of Participants With Potentially Clinically Significant Changes in Vital Signs
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.
Measured: Part A: Days 1, 2, 3, 4, 5, 6, 7, 9 and 11; Part B: Days 1, 2-13, 15, 16, 18, 20, 24
Number of Participants With Potentially Clinically Significant Changes in Electrocardiogram (ECG) Parameters
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
Measured: Part A: Days 1, 2, 3,5, 7 and 11; Part B: Days 1, 2, 4, 6, 8, 10, and 12,24
Number of Participants With Potentially Clinically Significant Changes in Clinical Laboratory Parameters
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 lipoprotein (HDL), Low-density lipoprotein (LDL), Urinalysis: Protein, Glucose, Blood Leukocyte esterase, Specific gravity, pH,Microscopic examination of the sediment if blood, protein or leukocytes esterase are positive on the dipstick; Other Analyses: Urine test for alcohol, Urine test for drugs of abuse, Pregnancy test
Measured: Part A: Days 2, 4, 7 and 11; Part B: Days 3, 7, 10, 14, 16, 24
Maximum Observed Plasma Concentration (Cmax)
PK parameters were derived from BMS-986251 concentration versus time data measured at the time points specified
Measured: Part A: Days 1, 2, 3, 4, 5, 6, 7, 9, 11; Part B : Day 1 and 14
Time of Maximum Observed Plasma Concentration (Tmax)
PK parameters were derived from BMS-986251 concentration versus time data measured at the time points specified
Measured: Part A: Days 1, 2, 3, 4, 5, 6, 7, 9, 11; Part B : Day 1 and 14
Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration [AUC(0-t)]
PK parameters were derived from BMS-986251 concentration versus time data measured at the time points specified
Measured: Part A: Days 1, 2, 3, 4, 5, 6, 7, 9, 11; Part B : Day 1 and 14
Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinite Time [AUC(0-inf)] (Part A)
PK parameters were derived from BMS-986251 concentration versus time data measured at the time points specified
Measured: Part A: Days 1, 2, 3, 4, 5, 6, 7, 9, 11
Terminal Elimination Half-life, Calculated as 0.693/Kel [t(1/2)]
PK parameters were derived from BMS-986251 concentration versus time data measured at the time points specified
Measured: Part A: Days 1, 2, 3, 4, 5, 6, 7, 9, 11; Part B : Day 14
Apparent (Oral) Clearance (CL/F) Calculated as Dose/[AUC(0-inf)] for Single Dose
PK parameters were derived from BMS-986251 concentration versus time data measured at the time points specified
Measured: Part A: Day 1, Part B: Day 14
Apparent Volume of Distribution at Terminal Phase [V(z)/F]
PK parameters were derived from BMS-986251 concentration versus time data measured at the time points specified
Measured: Part A: Days 1, 2, 3, 4, 5, 6, 7, 9, 11; Part B : Day 14
Cumulative Urinary Excretion (of the Unchanged Drug) [Ae(t)]
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
Measured: Part A: Days 1, 2, 3, 4, 5, 6, 7 ; Part B : Day 14
Amount Excreted Unchanged in Urine (% of Dose) [Fe(Urine)%]
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
Measured: Part A: Days 1, 2, 3, 4, 5, 6, 7 ; Part B : Day 14
Renal Clearance [CL(R)]
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
Measured: Part A: Days 1, 2, 3, 4, 5, 6, 7 ; Part B : Day 14
Area Under the Concentration-time Curve Over 24 Hours (One Dosing Interval) [AUC(0-24)] (Part B)
PK parameters were derived from BMS-986251 concentration versus time data measured at the time points specified
Measured: Part B : Days 1 and Day 14
Ratio of AUC(0-24) Following Last Dose to AUC(0-24) Following First Dose [AR[AUC(0-24)]] (Part B)
PK parameters were derived from BMS-986251 concentration versus time data measured at the time points specified
Measured: Part B : Day 14
Ratio of Cmax Following Last Dose to Cmax Following First Dose [AR(Cmax)] (Part B)
PK parameters were derived from BMS-986251 concentration versus time data measured at the time points specified
Measured: Part B : Day 14
Pre-dose Plasma Concentration (Cpre) (Part B)
PK parameters were derived from BMS-986251 concentration versus time data measured at the time points specified
Measured: Part B : Days 2-14
Inhibition at Time t [I(t)] (Part B)
Summary of IL-17 Inhibition in Whole Blood Pharmacodynamic (PD) Parameters
Measured: Part B : Days 16, 20, and 24

Secondary outcomes (5)

Maximum Observed Inhibition [I(Max)]
Summary of IL-17 Inhibition in Whole Blood Pharmacodynamic (PD) Parameters
Measured: Part A: Days 1, 2, 3, 5, 7, 11 ; Part B : Day 1, 2, 16, 20, 24
Time of Maximum Observed Inhibition [t(Imax)]
Summary of IL-17 Inhibition in Whole Blood Pharmacodynamic (PD) Parameters
Measured: Part A: Days 1, 2, 3, 5, 7, 11 ; Part B : Day 1, 2, 16, 20, 24
Time of Inhibition Above 50% [t(I>50%)]
Summary of IL-17 Inhibition in Whole Blood Pharmacodynamic (PD) Parameters
Measured: Part A: Days 1, 2, 3, 5, 7, 11 ; Part B : Day 1, 2, 16, 20, 24
Time of Inhibition Above 90% [t(I>90%)]
Summary of IL-17 Inhibition in Whole Blood Pharmacodynamic (PD) Parameters
Measured: Part A: Days 1, 2, 3, 5, 7, 11 ; Part B : Day 1, 2, 16, 20, 24
Pre-dose Inhibition [I(Pre)] (Part B)
Summary of IL-17 Inhibition in Whole Blood Pharmacodynamic (PD) Parameters
Measured: Part B : Days 2, 4, 7, and 14

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

2 Nov 201726 Jun 2018

First posted6 Nov 2017
Study start2 Nov 2017
Primary completion26 Jun 2018
Study completion26 Jun 2018

Why it stopped: Adverse change in the risk/benefit

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
More trials run by Bristol-Myers SquibbThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 38 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03329885
Sponsor's protocol ID: IM024-005
Other IDs: 2017-003408-38, 2017
Status last verified: Sep 2019
First submitted: 31 Oct 2017
Last updated: 21 Oct 2019
Results posted: Yes, on ClinicalTrials.gov
FDA-regulated drug: No
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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