Clinical trial NCT01313520: 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: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Arthritis, Rheumatoid
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2011-03-11
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Change From Baseline in the Volume Transfer Rate From the Blood Plasma to the Enhancing Synovium (Ktrans)
timeFrame: Baseline and week 14
Secondary outcomes:
measure: Percentage of Responders With a 20% Improvement From Baseline in American College of Rheumatology (ACR) Responder Criteria for Tender and Swollen Joints (ACR20).
timeFrame: Baseline and week 14
measure: Percentage of Responders With a 50% Improvement From Baseline in American College of Rheumatology (ACR) Responder Criteria for Tender and Swollen Joints (ACR50).
timeFrame: Baseline and week 14
measure: Change From Baseline in Standardized Z-scores of Composite Endpoint Consisting of Clinical Disease Activity Measure DAS28 CRP + Ktrans.
timeFrame: Baseline and Week 14
measure: 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.
timeFrame: Baseline and Week 14
Other outcomes:
measure: Change From Baseline in DAS28 CRP.
timeFrame: Baseline and Week 14
measure: Change From Baseline in RAMRIS Synovitis.
timeFrame: Baseline and Week 14
measure: Change From Baseline in RAMRIS Osteitis.
timeFrame: Baseline and Week 14
Locations:
Study officials:
References:
citation: Beals C, Baumgartner R, Peterfy C, Balanescu A, Mirea G, Harabagiu A, Popa S, Cheng A, Feng D, Ashton E, DiCarlo J, Vallee MH, Dardzinski BJ. Magnetic resonance imaging of the hand and wrist in a randomized, double-blind, multicenter, placebo-controlled trial of infliximab for rheumatoid arthritis: Comparison of dynamic contrast enhanced assessments with semi-quantitative scoring. PLoS One. 2017 Dec 13;12(12):e0187397. doi: 10.1371/journal.pone.0187397. eCollection 2017.
citation: MacIsaac KD, Baumgartner R, Kang J, Loboda A, Peterfy C, DiCarlo J, Riek J, Beals C. Pre-treatment whole blood gene expression is associated with 14-week response assessed by dynamic contrast enhanced magnetic resonance imaging in infliximab-treated rheumatoid arthritis patients. PLoS One. 2014 Dec 12;9(12):e113937. doi: 10.1371/journal.pone.0113937. eCollection 2014.