Efficacy and Safety Study of BMS-986142 in Patients With Moderate to Severe Rheumatoid Arthritis

Rheumatoid Arthritis Clinical Trial

Official title:

Phase 2, Randomized, Multi-Center, Double-Blind, Dose-Ranging, Placebo Controlled, Adaptive Design Study to Evaluate the Efficacy and Safety/Pharmacokinetics of BMS-986142 in Subjects With Moderate to Severe Rheumatoid Arthritis With an Inadequate Response to Methotrexate With or Without TNF Inhibitors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02638948
• Other study ID #: IM006-016
• Secondary ID: 2015-002887-17
• Status: Completed
• Phase: Phase 2
• Start date: February 16, 2016
• Est. completion date: May 3, 2018

Study information

• Verified date: May 2019
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether the study drug, BMS-986142, is safe and effective in treating moderate to severe rheumatoid arthritis in subjects with an inadequate response to methotrexate or methotrexate and up to 2 tumour necrosis factor (TNF) Inhibitors. Patients who qualify will be randomized to either one of 3 doses of BMS-986142 or placebo in 1:1:1 randomization for 12 weeks. Disease activity and safety will be assessed over the course of the study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 508
• Est. completion date: May 3, 2018
• Est. primary completion date: May 3, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

• Male and female age 18 and above

• Diagnosed with active rheumatoid arthritis (RA) by standard criteria at least 16 weeks before screening, have functional ACR class I-III

• Have an inadequate response to methotrexate

• In addition to an inadequate response to methotrexate have an inadequate response or intolerance to 1 but not more than 2 TNF inhibitors

• Have a minimum of 6 swollen and 6 tender joints (from 66/68 joint count)

• Have hsCRP of = 0.8 mg/dL (8mg/L) [by central laboratory values] or an ESR = 28 mm/hr

• Willing to use effective birth control for the entire length of the study

Exclusion Criteria:

• Diagnosed with juvenile Rheumatoid Arthritis

• Have been treated with other biologic treatment than a TNF inhibitor

• Active systemic bacterial, viral or fungal infection or evidence of prior or current Hepatitis B or C infection or HIV infection, latent bacterial, viral or fungal infections

• Have been treated with Intramuscular or Intra-articular glucocorticosteroids within 4 weeks of randomization

• Taking Oral steroids at dose above 10 mg/day of prednisone (or prednisone equivalents)

• Have other autoimmune disease other than RA like lupus, multiple sclerosis

• Have significant concurrent medical condition at the time of screening or baseline visit

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• BMS-986142
BMS986142 specific dose on specific days
• Placebo
Placebo of BMS-986142 specific dose on specific days
• Methotrexate
Methotrexate specific dose on specific days

Locations

Country	Name	City	State
Argentina	Instituto De Rehabilitacion Psicofisica	Buenos Aires
Argentina	Aprillus Asistencia e Investigacion	Capital Federal	Buenos Aires
Argentina	Local Institution	Capital Federal	Buenos Aires
Argentina	Instituto Reumatologico Strusberg	Cordoba
Austria	Universitaetsklinik Fuer Innere Medizin 3	Wien
Brazil	Local Institution	Curitiba	Parana
Brazil	Local Institution	Goiania	Goias
Brazil	Local Institution	Juiz de Fora	Minas Gerais
Brazil	Local Institution	Porto Alegre	RIO Grande DO SUL
Brazil	Local Institution	Porto Alegre	RIO Grande DO SUL
Brazil	Local Institution	Santo Andre	SAO Paulo
Brazil	Local Institution	Sao Paulo
Brazil	Local Institution	Sao Paulo
Canada	Aggarwal And Associates	Brampton	Ontario
Canada	Dr. Anil K Gupta Med Prof Corp	Toronto	Ontario
France	Local Institution	Corbeil Essonnes
France	Local Institution	Montpellier Cedex 5
France	Local Institution	Orleans cedex 2
France	Local Institution	Strasbourg Cedex
Germany	Asklepios Gesundheitszentrum	Elmshorn
Germany	Medizinsche Universitaetsklinik Freiburg	Freiburg
Germany	Smo.Md Gmbh	Magdeburg
Italy	Local Institution	Firenze
Italy	Local Institution	Padova
Japan	Local Institution	Chuo-ku	Tokyo
Japan	Local Institution	Fukuoka-shi	Fukuoka
Japan	Local Institution	Hamamatsu-shi	Shizuoka
Japan	Local Institution	Iruma-gun	Saitama
Japan	Local Institution	Itabashi-ku	Tokyo
Japan	Local Institution	Kato-shi	Hyogo
Japan	Local Institution	Kawachinagano	Osaka
Japan	Local Institution	Kawagoe-shi	Saitama
Japan	Local Institution	Kitakyushu-shi	Fukuoka
Japan	Local Institution	Kumamoto-shi	Kumamoto
Japan	Local Institution	Meguro-ku	Tokyo
Japan	Local Institution	Nagoya-shi	Aichi
Japan	Local Institution	Osaka-shi	Osaka
Japan	Local Institution	Osaki-shi
Japan	Local Institution	Sagamihara-shi	Kanagawa
Japan	Local Institution	Sapporo-shi	Hokkaido
Japan	Local Institution	Sapporo-shi	Hokkaido
Japan	Local Institution	Sapporo-shi	Hokkaido
Japan	Local Institution	Sasebo-shi	Nagasaki
Japan	Local Institution	Sendai-shi	Miyagi
Japan	Local Institution	Shinjuku-Ku	Tokyo
Korea, Republic of	Local Institution	Daegu
Korea, Republic of	Local Institution	Seoul
Mexico	Centro de Alta Especialidad en Reumatologia e Investigacion del Potosi S.C.	Distrito Federal
Mexico	Clinica de Investigacion en Reumatologia y Obesidad S.C.	Guadalajara	Jalisco
Mexico	Consultorio Privado de Especialidad	Guadalajara	Jalisco
Mexico	Unidad Reumatologica Las Americas, S.C. P.	Merida	Yucatan
Mexico	CINTRE - Centro de investigacion y tratamiento reumatologico, S.C.	Mexico City	Distrito Fededral
Mexico	Local Institution	Monterrey	Nuevo LEON
Mexico	Local Institution	Villahermosa	Tabasco
Netherlands	Maasstad Ziekenhuis Rotterdam	Rotterdam
Poland	Local Institution	Bialystok
Poland	Nzoz Osteo-Medic S.C. A. Racewicz, J.Supronik	Bialystok
Poland	Centrum Badan Klinicznych JCI Life Science Park	Krakow
Poland	Local Institution	Lublin
Poland	Local Institution	Nadarzyn
Poland	Local Institution	Poznan
Poland	Local Institution	Warszawa
Poland	Local Institution	Warszawa
Poland	Narodowy Instytut Geriatrii, Reumatologii i Rehabilitacji	Warszawa
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Saint-Petersburg
Russian Federation	Local Institution	St Petersburg
Russian Federation	Local Institution	Tolyatti
South Africa	Local Institution	Benoni	Gauteng
South Africa	Local Institution	Cape Town	Western CAPE
South Africa	Local Institution	George	Western CAPE
South Africa	Local Institution	Somerset West	Western CAPE
Spain	Local Institution	A Coruna
Spain	Fundacion Jimenez Diaz	Madrid
Spain	Local Institution	Santiago Compostela
Taiwan	Local Institution	Taichung
Taiwan	Local Institution	Taipei
United States	Albuquerque Center For Rheumatology	Albuquerque	New Mexico
United States	Albuquerque Clinical Trials	Albuquerque	New Mexico
United States	Pharma Tex Research	Amarillo	Texas
United States	Tekton Research Inc	Austin	Texas
United States	East Penn Rheumatology	Bethlehem	Pennsylvania
United States	Altoona Center For Clinical Research	Duncansville	Pennsylvania
United States	St. Joseph Heritage Medical Group	Fullerton	California
United States	Aa Mrc Llc	Grand Blanc	Michigan
United States	C.V Mehta M.D Medical Corp	Hemet	California
United States	HCP Clinical Research, LLC	Huntington Beach	California
United States	Rheumatology Associates Of North Alabama, P.C.	Huntsville	Alabama
United States	West Tennessee Research Institute	Jackson	Tennessee
United States	North Georgia Rheumatology Group	Lawrenceville	Georgia
United States	Southwest Rheumatology Research LLC	Mesquite	Texas
United States	Coral Research Clinic Corp	Miami	Florida
United States	Leon Medical Research	Miami	Florida
United States	San Marcus Research Clinic, Inc.	Miami	Florida
United States	Precision Research Organization	Miami Lakes	Florida
United States	Paramount Medical Research & Consulting, Llc	Middleburg Heights	Ohio
United States	Arthritis And Diabetes Clinic	Monroe	Louisiana
United States	The Arthritis Center	Palm Harbor	Florida
United States	Vizae Clinical Trials Management	Pembroke Pines	Florida
United States	Integral Rheumatology & Immunology Specialists	Plantation	Florida
United States	Advanced Rheumatology & Arthritis Research Center, P.C	Wexford	Pennsylvania
United States	Clinical Pharmacology Study Group	Worcester	Massachusetts
United States	Local Institution	Wyomissing	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Argentina,  Austria,  Brazil,  Canada,  France,  Germany,  Italy,  Japan,  Korea, Republic of,  Mexico,  Netherlands,  Poland,  Russian Federation,  South Africa,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Week 12	ACR responses are assessed with a composite rating scale of the American College of Rheumatology that includes 7 variables: tender joint count (TJC); swollen joint count (SJC); levels of an acute phase reactant C-reactive Protein levels (CRP); participant's assessment of pain; participant's global assessment of disease activity; physician's global assessment of disease activity; participant's assessment of physical function by health assessment questionnaire disability index (HAQ-DI). ACR20 is defined as achieving at least 20% improvement in both TJC and SJC, and at least 20% improvement in at least 3 of the 5 other assessments of the ACR. Percentage of Participants achieving ACR20 = (number of participants with measure/event of interest)/(number of particpants in the analysis)*100	Week 12
Primary	Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response at Week 12	ACR responses are assessed with a composite rating scale of the American College of Rheumatology that includes 7 variables: TJC; SJC; levels of an acute phase reactant (CRP level); participant's assessment of pain; participant's global assessment of disease activity; physician's global assessment of disease activity; participant's assessment of physical function by HAQ--DI. ACR70 is defined as achieving at least 70% improvement in both TJC and SJC, and at least 70% improvement in at least 3 of the 5 other assessments of the ACR. Percentage of Participants achieving ACR70 = (number of participants with measure/event of interest)/(number of particpants in the analysis)*100	Week 12
Secondary	Percentage of Participants Achieving American College of Rheumatology 20% Response Over Time From Baseline to Week 12	ACR responses are assessed with a composite rating scale of the American College of Rheumatology that includes 7 variables: tender joint count (TJC); swollen joint count (SJC); levels of an acute phase reactant C-reactive Protein levels (CRP); participant's assessment of pain; participant's global assessment of disease activity; physician's global assessment of disease activity; participant's assessment of physical function by health assessment questionnaire disability index (HAQ-DI). ACR20 is defined as achieving at least 20% improvement in both TJC and SJC, and at least 20% improvement in at least 3 of the 5 other assessments of the ACR. Percentage of Participants achieving ACR20 = (number of participants with measure/event of interest)/(number of particpants in the analysis)*100	Baseline, Day 15, Day 29, Day 57, Day 85
Secondary	Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response Over Time From Baseline to Week 12	ACR responses are assessed with a composite rating scale of the American College of Rheumatology that includes 7 variables: TJC; SJC; levels of an acute phase reactant (CRP level); participant's assessment of pain; participant's global assessment of disease activity; physician's global assessment of disease activity; participant's assessment of physical function by HAQ--DI. ACR70 is defined as achieving at least 50% improvement in both TJC and SJC, and at least 50% improvement in at least 3 of the 5 other assessments of the ACR. Percentage of Participants achieving ACR50 = (number of participants with measure/event of interest)/(number of particpants in the analysis)*100	Baseline, Day 15, Day 29, Day 57, Day 85
Secondary	Percentage of Participants Achieving American College of Rheumatology 70% Response Over Time From Baseline to Week 12	ACR responses are assessed with a composite rating scale of the American College of Rheumatology that includes 7 variables: TJC; SJC; levels of an acute phase reactant (CRP level); participant's assessment of pain; participant's global assessment of disease activity; physician's global assessment of disease activity; participant's assessment of physical function by HAQ--DI. ACR70 is defined as achieving at least 70% improvement in both TJC and SJC, and at least 70% improvement in at least 3 of the 5 other assessments of the ACR. Percentage of Participants achieving ACR70 = (number of participants with measure/event of interest)/(number of particpants in the analysis)*100	Baseline, Day 15, Day 29, Day 57, Day 85
Secondary	Percentage of Participants Achieving < 2.6 Response in Disease Activity Score for 28 Joints -C-Reactive Protein (DAS28--CRP) Score at Week 12	DAS28 is a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); General health (GH) assessment by the participant assessed from the ACR rheumatoid arthritis (RA) core set questionnaire (participant global assessment) in 100 mm visual analog scale (VAS). Marker of inflammation assessed by the high sensitivity C-reactive protein (hs-CRP) in mg/L. The DAS28 score provides a number indicating the current disease activity of the RA. DAS28 total score ranges from 2-10. A DAS28 score above 5.1 means high disease activity, whereas a DAS28 score below 3.2 indicates low disease activity and a DAS28 score below 2.6 means disease remission.	Week 12
Secondary	Percentage of Participants Achieving < 2.6 Response in Disease Activity Score for 28 Joints Erythrocyte Sedimentation Rate (DAS28--ESR) Score at Week 12	DAS28-ESR is a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); General health (GH) assessment by the participant assessed from the ACR RA core set questionnaire (participant global assessment) in 100 mm VAS; Marker of inflammation assessed by ESR in mm/hr. The DAS28-ESR score provides a number indicating the current disease activity of the RA. DAS28-ESR total score ranges from 2-10. A DAS28-ESR score above 5.1 means high disease activity, DAS28-ESR score below 3.2 indicates low disease activity and DAS28-ESR score below 2.6 means disease remission.	Week 12
Secondary	Percentage of Participants Achieving <= 2.8 Response in Clinical Disease Activity Index (CDAI) Score at Week 12	CDAI is a composite index constructed to measure clinical remission in RA that does not include a laboratory test, and is a numerical summation of 4 components: TJC (28 joints), SJC (28 joints), Participant's Global Assessment of Disease Activity VAS (in cm), and Physician's Global Assessment of Disease VAS (in cm). Total scores ranges from 0 to 76 with a negative change in CDAI score indicating an improvement in disease activity and a positive change in score indicating a worsening of disease activity.	Week 12
Secondary	Percentage of Participants Achieving <= 3.3 Response in Simple Disease Activity Index (SDAI) Score at Week 12	The SDAI is the numerical sum of five outcome parameters: TJC and SJC based on a 28-joint assessment, patient global assessment (PtGA) and physician global assessment (PGA) assessed on a VAS scale ranging from 0 to 10 cm, where higher scores indicate greater affection due to disease activity, and CRP measured in terms of milligram per deciliter (mg/dL). SDAI total score ranges from 0 to 86. SDAI <= 3.3 indicates disease remission, > 3.4 to 11 indicates low disease activity, >11 to 26 indicates moderate disease activity, and >26 indicates high disease activity.	Week 12
Secondary	Percentage of Participants Achieving Boolean Remission Criteria at Week 12	Boolean remission criteria was defined as: tender joint count28 <= 1; swollen joint count28 <= 1; physician's global assessment <= 1; and CRP <= 1 mg/deciliter.	Week 12
Secondary	Change From Baseline in DAS28-CRP Score Over Time up to Week 12	DAS28 is a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); General health (GH) assessment by the participant assessed from the ACR rheumatoid arthritis (RA) core set questionnaire (participant global assessment) in 100 mm visual analog scale (VAS). Marker of inflammation assessed by the high sensitivity C-reactive protein (hs-CRP) in mg/L. The DAS28 score provides a number indicating the current disease activity of the RA. DAS28 total score ranges from 2-10. A DAS28 score above 5.1 means high disease activity, whereas a DAS28 score below 3.2 indicates low disease activity and a DAS28 score below 2.6 means disease remission.	Baseline, Day 85 (Week 12)
Secondary	Change From Baseline in DAS28-ESR Score Over Time up to Week 12	DAS28-ESR is a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); General health (GH) assessment by the participant assessed from the ACR RA core set questionnaire (participant global assessment) in 100 mm VAS; Marker of inflammation assessed by ESR in mm/hr. The DAS28-ESR score provides a number indicating the current disease activity of the RA. DAS28-ESR total score ranges from 2-10. A DAS28-ESR score above 5.1 means high disease activity, DAS28-ESR score below 3.2 indicates low disease activity and DAS28-ESR score below 2.6 means disease remission.	Baseline, Week 12
Secondary	Change From Baseline in CDAI Score Over Time up to Week 12	CDAI is a composite index constructed to measure clinical remission in RA that does not include a laboratory test, and is a numerical summation of 4 components: TJC (28 joints), SJC (28 joints), Participant's Global Assessment of Disease Activity VAS (in cm), and Physician's Global Assessment of Disease VAS (in cm). Total scores ranges from 0 to 76 with a negative change in CDAI score indicating an improvement in disease activity and a positive change in score indicating a worsening of disease activity.	Baseline, Week 12
Secondary	Change From Baseline in SDAI Score Over Time up to Week 12	The SDAI is the numerical sum of five outcome parameters: TJC and SJC based on a 28-joint assessment, PtGA and PGA assessed on a VAS scale ranging from 0 to 10 cm, where higher scores indicate greater affection due to disease activity, and CRP measured in terms of mg/dL. SDAI total score ranges from 0 to 86. SDAI <= 3.3 indicates disease remission, > 3.4 to 11 indicates low disease activity, >11 to 26 indicates moderate disease activity, and >26 indicates high disease activity.	Baseline, Week 12
Secondary	Number of Participants With Adverse Events (AEs), and Serious AEs (SAEs)	An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death, initial or prolonged inpatient hospitalization, life-threatening experience (immediate risk of dying), persistent or significant disability/incapacity, or a congenital anomaly, or a medically important event.	Up to 30 days after treatment discontinuation
Secondary	Trough Observed Plasma Concentration (Ctrough) of BMS-986142	Ctrough was defined as trough observed plasma concentration.	Week 4, 8, and 12
Secondary	Mean Change From Baseline in Rheumatoid Arthritis Magnetic Resonance Imaging Scoring System (RAMRIS) Scores for Synovitis at Week 4 and 12	Synovitis is assessed in 3 wrist regions (A. the distal radioulnar joint; B. the radiocarpal joint; C. the intercarpal and carpometacarpophalangeal, CMC, joints) and in each MCP joint. For each wrist region, possible score ranges from 0-3, with 0=normal, 1=mild, 2=moderate, and 3=severe damage. The total synovitis score per wrist=the sum of the individual scores for the 3 wrist regions. Minimum score per wrist ranges from 0, indicating no damage, to 9 (score of 3*3 wrist regions), indicating most severe damage. A negative change from baseline indicates improvement.	Week 4 and Week 12
Secondary	Mean Change From Baseline in Rheumatoid Arthritis Magnetic Resonance Imaging Scoring System (RAMRIS) Scores for Osteitis at Week 4 and 12	Osteitis was assessed at a total of 23 anatomic locations: 15 in 1 wrist and 8 in the hand of the same side. Each site is scored in 1.0 increments from 0 to 3, indicating involvement of original articular bone. The total score for the hands/wrists is the sum of the individual scores for each location. Thus the maximum score achievable per hand/wrist is 23 (total number of anatomic locations) * 3 (maximum per joint)=69. Minimum score=0, indicating normal. Increasing score=greater severity. A negative change from baseline indicates improvement.	Week 4, and Week 12
Secondary	Mean Change From Baseline in Rheumatoid Arthritis Magnetic Resonance Imaging Scoring System (RAMRIS) Scores for Bone Erosion at Week 4 and 12	Bone erosion assessed at a total of 23 anatomic locations: 15 in 1 wrist and 8 in the hand of the same side. Each site is scored in 1.0 increments from 0 (no damage) to 10 (severe damage) according to erosion of the original articular bone (each unit=10% loss of articular bone). The total erosion score for the hands/wrists is the sum of the individual scores for each location. Thus the maximum score achievable per hand/wrist is 230. Increasing score=greater severity.A negative change from baseline indicates improvement.	Week 4 and Week 12
Secondary	Mean Change From Baseline in Rheumatoid Arthritis Magnetic Resonance Imaging Scoring System (RAMRIS) Scores for Cartilage Loss at Week 4 and 12	Cartilage loss was assessed by MRI. Scans of 25 joints were read and scored for each participant by assessors. Scores for each location ranged 0-4 on a 9-point scale, with 0= no cartilage loss and 4= complete cartilage loss. Total score was the sum of the 25 individual scores and ranged 0-100 with 0= no cartilage loss and 100= most severe cartilage loss. A negative change from baseline indicates improvement.	Week 4, and Week12

External Links

•   BMS Clinical Trial Patient Recruiting
•   Investigator Inquiry Form