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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02638948
Recruitment Status : Completed
First Posted : December 23, 2015
Results First Posted : May 28, 2019
Last Update Posted : May 28, 2019
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

Tracking Information
First Submitted Date  ICMJE December 21, 2015
First Posted Date  ICMJE December 23, 2015
Results First Submitted Date  ICMJE May 1, 2019
Results First Posted Date  ICMJE May 28, 2019
Last Update Posted Date May 28, 2019
Actual Study Start Date  ICMJE February 16, 2016
Actual Primary Completion Date May 3, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 2, 2019)
  • Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Week 12 [ Time Frame: 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
  • Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response at Week 12 [ Time Frame: 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
Original Primary Outcome Measures  ICMJE
 (submitted: December 21, 2015)
  • Proportion of subjects who achieve ACR70 response rate [ Time Frame: At week 12 ]
  • Proportion of subjects who achieve ACR20 response rate [ Time Frame: At week 12 ]
Change History Complete list of historical versions of study NCT02638948 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 2, 2019)
  • Percentage of Participants Achieving American College of Rheumatology 20% Response Over Time From Baseline to Week 12 [ Time Frame: Baseline, Day 15, Day 29, Day 57, Day 85 ]
    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
  • Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response Over Time From Baseline to Week 12 [ Time Frame: Baseline, Day 15, Day 29, Day 57, Day 85 ]
    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
  • Percentage of Participants Achieving American College of Rheumatology 70% Response Over Time From Baseline to Week 12 [ Time Frame: Baseline, Day 15, Day 29, Day 57, Day 85 ]
    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
  • Percentage of Participants Achieving < 2.6 Response in Disease Activity Score for 28 Joints -C-Reactive Protein (DAS28--CRP) Score at Week 12 [ Time Frame: 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.
  • Percentage of Participants Achieving < 2.6 Response in Disease Activity Score for 28 Joints Erythrocyte Sedimentation Rate (DAS28--ESR) Score at Week 12 [ Time Frame: 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.
  • Percentage of Participants Achieving <= 2.8 Response in Clinical Disease Activity Index (CDAI) Score at Week 12 [ Time Frame: 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.
  • Percentage of Participants Achieving <= 3.3 Response in Simple Disease Activity Index (SDAI) Score at Week 12 [ Time Frame: 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.
  • Percentage of Participants Achieving Boolean Remission Criteria at Week 12 [ Time Frame: 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.
  • Change From Baseline in DAS28-CRP Score Over Time up to Week 12 [ Time Frame: Baseline, Day 85 (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.
  • Change From Baseline in DAS28-ESR Score Over Time up to Week 12 [ Time Frame: Baseline, 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.
  • Change From Baseline in CDAI Score Over Time up to Week 12 [ Time Frame: Baseline, 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.
  • Change From Baseline in SDAI Score Over Time up to Week 12 [ Time Frame: Baseline, 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.
  • Number of Participants With Adverse Events (AEs), and Serious AEs (SAEs) [ Time Frame: Up to 30 days after treatment discontinuation ]
    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.
  • Trough Observed Plasma Concentration (Ctrough) of BMS-986142 [ Time Frame: Week 4, 8, and 12 ]
    Ctrough was defined as trough observed plasma concentration.
  • Mean Change From Baseline in Rheumatoid Arthritis Magnetic Resonance Imaging Scoring System (RAMRIS) Scores for Synovitis at Week 4 and 12 [ Time Frame: Week 4 and Week 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.
  • Mean Change From Baseline in Rheumatoid Arthritis Magnetic Resonance Imaging Scoring System (RAMRIS) Scores for Osteitis at Week 4 and 12 [ Time Frame: Week 4, and Week 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.
  • Mean Change From Baseline in Rheumatoid Arthritis Magnetic Resonance Imaging Scoring System (RAMRIS) Scores for Bone Erosion at Week 4 and 12 [ Time Frame: Week 4 and Week 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.
  • Mean Change From Baseline in Rheumatoid Arthritis Magnetic Resonance Imaging Scoring System (RAMRIS) Scores for Cartilage Loss at Week 4 and 12 [ Time Frame: Week 4, and Week12 ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 21, 2015)
  • Proportion of subjects who achieve ACR20 [ Time Frame: Baseline to week 12 ]
  • Proportion of subjects who achieve ACR50 [ Time Frame: Baseline to week 12 ]
  • Proportion of subjects who achieve ACR70 [ Time Frame: Baseline to week 12 ]
  • Proportion of subjects who achieve DAS28- C-reactive protein (CRP) < 2.6 [ Time Frame: Baseline to week 12 ]
  • Proportion of subjects who achieve DAS28- erythrocyte sedimentation rate (ESR) < 2.6 [ Time Frame: Baseline to week 12 ]
  • Proportion of subjects who achieve clinical disease activity index (CDAI) ≤ 2.8 [ Time Frame: Baseline to week 12 ]
  • Proportion of subjects who achieve simplified disease index (SDAI) ≤ 3.3 [ Time Frame: Baseline to week 12 ]
  • Proportion of subjects who achieve Boolean Remission [ Time Frame: Baseline to week 12 ]
  • Change from baseline in DAS28-CRP score [ Time Frame: Upto week 12 ]
  • Change from baseline in DAS28-ESR score [ Time Frame: Upto week 12 ]
  • Change from baseline in CDAI score [ Time Frame: Upto week 12 ]
  • Change from baseline in SDAI score [ Time Frame: Upto week 12 ]
  • Change from baseline in rheumatoid arthritis magnetic resonance imaging scoring system (RAMRIS) scores of synovitis [ Time Frame: Upto week 12 ]
  • Change from baseline in RAMRIS scores of osteitis (bone marrow edema) [ Time Frame: Upto week 12 ]
  • Change from baseline in RAMRIS scores of bone erosion [ Time Frame: Upto week 12 ]
  • Change from baseline in RAMRIS scores of cartilage loss (joint-space narrowing) [ Time Frame: Upto week 12 ]
  • Incidence of Adverse Events (AEs), Serious AEs, pre-established events of special Interest, vital signs, electrocardiogram (ECG), abnormalities in general laboratory tests [ Time Frame: Upto week 16 ]
  • Plasma concentration of BMS-986142 [ Time Frame: Upto week 12 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy and Safety Study of BMS-986142 in Patients With Moderate to Severe Rheumatoid Arthritis
Official Title  ICMJE 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
Brief 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Rheumatoid Arthritis
Intervention  ICMJE
  • Drug: BMS-986142
    BMS986142 specific dose on specific days
  • Drug: Placebo
    Placebo of BMS-986142 specific dose on specific days
  • Drug: Methotrexate
    Methotrexate specific dose on specific days
Study Arms  ICMJE
  • Placebo Comparator: Placebo
    Placebo + Methotrexate dose as specified
    Interventions:
    • Drug: Placebo
    • Drug: Methotrexate
  • Experimental: Dose Level 1
    BMS-986142 at dose level 1+ Methotrexate as specified
    Interventions:
    • Drug: BMS-986142
    • Drug: Methotrexate
  • Experimental: Dose Level 2
    BMS-986142 at dose level 2 + Methotrexate as specified
    Interventions:
    • Drug: BMS-986142
    • Drug: Methotrexate
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 2, 2019)
508
Original Estimated Enrollment  ICMJE
 (submitted: December 21, 2015)
408
Actual Study Completion Date  ICMJE May 3, 2018
Actual Primary Completion Date May 3, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 120 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Austria,   Brazil,   Canada,   France,   Germany,   Italy,   Japan,   Korea, Republic of,   Mexico,   Netherlands,   Poland,   Russian Federation,   South Africa,   Spain,   Taiwan,   United States
Removed Location Countries Belgium
 
Administrative Information
NCT Number  ICMJE NCT02638948
Other Study ID Numbers  ICMJE IM006-016
2015-002887-17 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Bristol-Myers Squibb
Study Sponsor  ICMJE Bristol-Myers Squibb
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Bristol Myers Squibb Bristol-Myers Squibb
PRS Account Bristol-Myers Squibb
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP