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)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01313520
First received: February 25, 2011
Last updated: March 26, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Arthritis, Rheumatoid
Drug: Infliximab
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Change From Baseline in the Volume Transfer Rate From the Blood Plasma to the Enhancing Synovium (Ktrans) [ Time Frame: Baseline and week 14 ] [ Designated as safety issue: No ]
    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).


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.


Other Outcome Measures:
  • Change From Baseline in DAS28 CRP. [ Time Frame: Baseline and Week 14 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.


Enrollment: 61
Study Start Date: March 2011
Study Completion Date: March 2012
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Infliximab
3 mg/kg of Infliximab intravenous infusion
Drug: Infliximab
3 mg/kg of Infliximab at Weeks 0, 2, 6, 14 via intravenous infusion
Other Names:
  • SCH 215596
  • Remicade
Placebo Comparator: Placebo
saline via intravenous infusion
Drug: Placebo
250 mL of 0.9% sodium chloride at Weeks 0, 2, 6, 14 via intravenous infusion

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01313520     History of Changes
Other Study ID Numbers: P08136, 2011-000079-14
Study First Received: February 25, 2011
Results First Received: February 12, 2013
Last Updated: March 26, 2014
Health Authority: Romania: National Medicines Agency

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Infliximab
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Dermatologic Agents
Gastrointestinal Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on September 14, 2014