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A Study to Evaluate the Effectiveness of Infliximab and Changes in Hand and Wrist Magnetic Resonance Imaging (MRI) in Participants With Active Rheumatoid Arthritis (RA) (P08136)

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ClinicalTrials.gov Identifier: NCT01313520
Recruitment Status : Completed
First Posted : March 11, 2011
Results First Posted : July 8, 2013
Last Update Posted : May 10, 2017
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Tracking Information
First Submitted Date  ICMJE February 25, 2011
First Posted Date  ICMJE March 11, 2011
Results First Submitted Date  ICMJE February 12, 2013
Results First Posted Date  ICMJE July 8, 2013
Last Update Posted Date May 10, 2017
Actual Study Start Date  ICMJE March 1, 2011
Actual Primary Completion Date March 1, 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 25, 2013)
Change From Baseline in the Volume Transfer Rate From the Blood Plasma to the Enhancing Synovium (Ktrans) [ Time Frame: Baseline and week 14 ]
Dynamic Contrast Enhanced (DCE) Magnetic Resonance Imaging (MRI) was performed on one hand at baseline, and then at treatment week 14 to measure the rate constant of transfer of contrast (Ktrans).
Original Primary Outcome Measures  ICMJE
 (submitted: March 10, 2011)
Change From Baseline in the Volume Transfer Rate From the Blood Plasma to the Enhancing Synovium (Ktrans) [ Time Frame: up to 14 weeks ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 19, 2015)
  • Percentage of Responders With a 20% Improvement From Baseline in American College of Rheumatology (ACR) Responder Criteria for Tender and Swollen Joints (ACR20). [ Time Frame: Baseline and week 14 ]
    ACR20 requires that both tender and swollen joint counts improve by at least 20% from baseline, as well as a 20% improvement in at least 3 other core measures from the following: pain, patient's and physician's global assessment, physical disability and C-reactive protein (CRP).
  • Percentage of Responders With a 50% Improvement From Baseline in American College of Rheumatology (ACR) Responder Criteria for Tender and Swollen Joints (ACR50). [ Time Frame: Baseline and week 14 ]
    ACR50 requires that both tender and swollen joint counts improve by at least 50% from baseline, as well as a 50% improvement in at least 3 other core measures from the following: pain, patient's and physician's global assessment, physical disability and CRP.
  • Change From Baseline in Standardized Z-scores of Composite Endpoint Consisting of Clinical Disease Activity Measure DAS28 CRP + Ktrans. [ Time Frame: Baseline and Week 14 ]
    Clinical disease activity score (DAS28 CRP) is a composite index of the following: number of tender joints (28 joint count), number of swollen joints (28 joint count), Patient Global Assessment of Disease Status (GADP) on a 100 mm visual analog scale (VAS) and concentration of CRP. Ktrans is the volume transfer rate from the blood plasma to the enhancing synovium. The individual endpoints are standardized using z-scores, then the z-scores are averaged to create a composite endpoint by use of O'Brien's global statistic.
  • Change From Baseline in Standardized Z-scores of Composite Endpoint Consisting of Clinical Disease Activity Measure DAS28 CRP + Rheumatoid Arthritis MRI Score (RAMRIS) Synovitis + RAMRIS Osteitis. [ Time Frame: Baseline and Week 14 ]
    DAS28 CRP is a composite index of the following: number of tender joints (28 joint count), number of swollen joints (28 joint count), GADP on a 100 mm VAS and concentration of CRP. RAMRIS Synovitis is an ordinal scoring system of hand synovitis that is scored from 0 to 3 in 8 locations, ranging from 0 to 24 total. RAMRIS Osteitis is an ordinal scoring system of hand osteitis that is scored from 0 to 3 in 25 locations, ranging from 0 to 75 total. The individual endpoints are standardized using z-scores, then the z-scores are averaged to create a composite endpoint by use of O'Brien's global statistic.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures
 (submitted: April 25, 2013)
  • Change From Baseline in DAS28 CRP. [ Time Frame: Baseline and Week 14 ]
    DAS28 CRP is a composite index of the following: number of tender joints (28 joint count), number of swollen joints (28 joint count), GADP on a 100 mm VAS and concentration of serum CRP. Scores can range from 2-10; with higher values corresponding to higher disease activity, and lower values to better outcomes.
  • Change From Baseline in RAMRIS Synovitis. [ Time Frame: Baseline and Week 14 ]
    RAMRIS Synovitis is an ordinal scoring system of hand synovitis that is scored from 0 to 3 in 8 locations. The scores can range from 0 to 24, with higher values corresponding to higher disease activity, and lower values to better outcomes.
  • Change From Baseline in RAMRIS Osteitis. [ Time Frame: Baseline and Week 14 ]
    RAMRIS Osteitis is an ordinal scoring system of hand osteitis that is scored from 0 to 3 in 25 locations. The scores can range from 0 to 75, with higher values corresponding to higher disease activity, and lower values to better outcomes.
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Evaluate the Effectiveness of Infliximab and Changes in Hand and Wrist Magnetic Resonance Imaging (MRI) in Participants With Active Rheumatoid Arthritis (RA) (P08136)
Official Title  ICMJE A Randomized Clinical Trial to Study the Effects of Infliximab on Clinical Efficacy and Hand and Wrist Magnetic Resonance Imaging (MRI) in Patients With Active Rheumatoid Arthritis (RA)(Protocol No. P08136)
Brief Summary This is a study to compare the effect of infliximab versus placebo on synovial inflammation as measured by dynamic contrast enhanced (DCE)-MRI of one wrist. The primary hypothesis is that over 14 weeks of therapy, the change from baseline in the volume transfer rate in enhancing synovium is larger due to treatment with infliximab than with placebo.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Arthritis, Rheumatoid
Intervention  ICMJE
  • Drug: Infliximab
    3 mg/kg of Infliximab at Weeks 0, 2, 6, 14 via intravenous infusion
    Other Names:
    • SCH 215596
    • Remicade
  • Drug: Placebo
    250 mL of 0.9% sodium chloride at Weeks 0, 2, 6, 14 via intravenous infusion
Study Arms  ICMJE
  • Experimental: Infliximab
    3 mg/kg of Infliximab intravenous infusion
    Intervention: Drug: Infliximab
  • Placebo Comparator: Placebo
    saline via intravenous infusion
    Intervention: Drug: Placebo
Publications *

*   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: April 10, 2012)
61
Original Estimated Enrollment  ICMJE
 (submitted: March 10, 2011)
60
Actual Study Completion Date  ICMJE March 1, 2012
Actual Primary Completion Date March 1, 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Must have a clinical diagnosis of rheumatoid arthritis for at least 6 months
  • Must have at least 6 tender joints AND 6 swollen joints
  • Has a C-reactive protein ≥ 1.0 mg/L OR Erythrocyte Sedimentation Rate (ESR) ≥ 28 mm/hr
  • Baseline MRI must show evidence of synovitis in the wrist
  • Must have screening laboratory tests within acceptable levels
  • Women of childbearing potential and all men must agree to use a medically accepted method of contraception prior to entering the study and continue throughout study up to 6 weeks after study completion
  • Must meet tuberculosis (TB) screening criteria
  • Have received methotrexate therapy for ≥ 3 months; dose must be stable for at least 8 weeks
  • If taking the a disease modifying anti-rheumatic drug (DMARD) in combination with methotrexate must be on a stable dose
  • Must have a clinically acceptable 12 lead electrocardiogram (ECG)
  • If taking oral corticosteroids must be on a stable dose equivalent to ≤10 mg of prednisone (or prednisolone) per day for ≥2 weeks
  • If taking daily non-steroidal anti-inflammatory drug (NSAID) must be on a stable dose for ≥2 weeks; if taking NSAID on an as-needed basis must agree to discontinue use for at least 3 days and use only acetaminophen for breakthrough pain for 3 days before each MRI and clinic visit
  • If received biological therapies, the last dose of these drugs was to be received ≥ 3 months prior to the baseline visit AND the reason for discontinuations was not for safety considerations OR lack of efficacy

Exclusion Criteria:

  • Are pregnant, intend to become pregnant, or are breastfeeding
  • Has inflammatory arthritis other than RA
  • Has uncontrolled hypertension
  • Has moderate or severe congestive heart failure
  • Has a history of or current signs and/or symptoms of severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiac, neurological, cerebral, or psychiatric disease
  • Has a history of demyelinating disease or symptoms suggestive of multiple sclerosis or optic neuritis
  • Is currently participating in another clinical study or have participated in a clinical study (e.g., laboratory or clinical evaluation) within 4 weeks
  • Has history of any tumor with the exception of adequately treated basal cell carcinoma or carcinoma in situ of the cervix
  • Has a history of any latent or active granulomatous infection including histoplasmosis, or coccidiomycosis
  • Had a non-tuberculous mycobacterial infection or opportunistic infection (e.g. cytomegalovirus, Pneumocystis carinii, aspergillosis) within 6 months
  • Has a history of an infected joint prosthesis which has not been removed or replaced
  • Has a known hypersensitivity to human immunoglobulin proteins or other components of infliximab
  • Has received rituximab or natalizumab
  • Has known claustrophobia or other contraindication to MRI
  • Does not meet washout period guidelines for previous treatments/injections/vaccinations
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (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 Not Provided
Removed Location Countries Moldova, Republic of,   Romania
 
Administrative Information
NCT Number  ICMJE NCT01313520
Other Study ID Numbers  ICMJE P08136
2011-000079-14 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description:

http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf

http://engagezone.msd.com/ds_documentation.php

Responsible Party Merck Sharp & Dohme Corp.
Study Sponsor  ICMJE Merck Sharp & Dohme Corp.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Merck Sharp & Dohme Corp.
Verification Date April 2017

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