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)

Arthritis, Rheumatoid Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01313520
• Other study ID #: P08136
• Secondary ID: 2011-000079-14
• Status: Completed
• Phase: Phase 2
• First received: February 25, 2011
• Last updated: October 19, 2015
• Start date: March 2011
• Est. completion date: March 2012

Study information

• Verified date: October 2015
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Health authority: Romania: National Medicines Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 61
• Est. completion date: March 2012
• Est. primary completion date: March 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid

Intervention

Drug:
• Infliximab
3 mg/kg of Infliximab at Weeks 0, 2, 6, 14 via intravenous infusion
• Placebo
250 mL of 0.9% sodium chloride at Weeks 0, 2, 6, 14 via intravenous infusion

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change From Baseline in DAS28 CRP.	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.	Baseline and Week 14	No
Other	Change From Baseline in RAMRIS Synovitis.	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.	Baseline and Week 14	No
Other	Change From Baseline in RAMRIS Osteitis.	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.	Baseline and Week 14	No
Primary	Change From Baseline in the Volume Transfer Rate From the Blood Plasma to the Enhancing Synovium (Ktrans)	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).	Baseline and week 14	No
Secondary	Percentage of Responders With a 20% Improvement From Baseline in American College of Rheumatology (ACR) Responder Criteria for Tender and Swollen Joints (ACR20).	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).	Baseline and week 14	No
Secondary	Percentage of Responders With a 50% Improvement From Baseline in American College of Rheumatology (ACR) Responder Criteria for Tender and Swollen Joints (ACR50).	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.	Baseline and week 14	No
Secondary	Change From Baseline in Standardized Z-scores of Composite Endpoint Consisting of Clinical Disease Activity Measure DAS28 CRP + Ktrans.	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.	Baseline and Week 14	No
Secondary	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.	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.	Baseline and Week 14	No