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)

Completed Phase 2 Results posted Last updated 10 May 2017

What this trial tests

Phase 2 trial testing Infliximab in Arthritis, Rheumatoid in 61 participants. Completed in 1 March 2012.

Timeline

1 March 2011

Primary endpoint
1 March 2012

1 March 2012

Quick facts

Lead sponsor	Merck Sharp & Dohme LLC
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	triple
Primary purpose	treatment
Enrollment	61
Start date	1 March 2011
Primary completion	1 March 2012
Estimated completion	1 March 2012

Drugs / interventions tested

• Infliximab (infliximab) — full drug profile →
• Placebo

Conditions studied

• Arthritis, Rheumatoid — all drugs for Arthritis, Rheumatoid →

Sponsor

Merck Sharp & Dohme LLC — full company profile →

Who can join

18 and older, any sex, with Arthritis, Rheumatoid. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline in the Volume Transfer Rate From the Blood Plasma to the Enhancing Synovium (Ktrans) Primary · 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).

Group	Value	95% CI
Infliximab	-0.2	-0.3 – -0.1
Placebo	0.1	-0.0 – 0.2

Percentage of Responders With a 20% Improvement From Baseline in American College of Rheumatology (ACR) Responder Criteria for Tender and Swollen Joints (ACR20). Secondary · 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).

Group	Value	95% CI
Infliximab	56.7	41.9 – 70.4
Placebo	32.3	20.3 – 47.0

Percentage of Responders With a 50% Improvement From Baseline in American College of Rheumatology (ACR) Responder Criteria for Tender and Swollen Joints (ACR50). Secondary · 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.

Group	Value	95% CI
Infliximab	20.0	10.7 – 34.2
Placebo	0	0 – 0

Change From Baseline in DAS28 CRP. Secondary · 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.

Group	Value	95% CI
Infliximab	-1.8	-2.2 – -1.5
Placebo	-0.8	-1.2 – -0.4

Change From Baseline in RAMRIS Synovitis. Secondary · 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.

Group	Value	95% CI
Infliximab	-2.30	0.64 – 1.55
Placebo	0.24	± 1.98

Change From Baseline in RAMRIS Osteitis. Secondary · 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.

Group	Value	95% CI
Infliximab	-3.10	-2 – -1.5
Placebo	0.48	-1 – -0.5

Change From Baseline in Standardized Z-scores of Composite Endpoint Consisting of Clinical Disease Activity Measure DAS28 CRP + Ktrans. Secondary · 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.

Group	Value	95% CI
Infliximab	-0.8	-1.3 – -0.3
Placebo	0.8	0.3 – 1.2

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. Secondary · 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 st

Group	Value	95% CI
Infliximab	-0.7	-1.3 – -0.2
Placebo	0.8	0.2 – 1.3

Adverse events — posted to ClinicalTrials.gov

Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Infliximab

Serious: 0/30 (0%)

Deaths: —

Placebo

Serious: 0/31 (0%)

Deaths: —

Other adverse events (4 terms — click to expand)

Reaction	System	Infliximab	Placebo
Joint Swelling	Musculoskeletal and connective tissue disorders	—	—
Palpitations	Cardiac disorders	—	—
Abdominal Pain	Gastrointestinal disorders	—	—
Headache	Nervous system disorders	—	—

Data from ClinicalTrials.gov NCT01313520 adverse events section.

Sponsor's own description

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.

Publications & conference data

5 peer-reviewed publications reference this trial (live from Europe PMC):

1. Biologics or tofacitinib for people with rheumatoid arthritis naive to methotrexate: a systematic review and network meta-analysis.
   Singh JA, Hossain A, Mudano AS, Tanjong Ghogomu E, et al · · 2017 · cited 44× · PMID 28481462 · DOI 10.1002/14651858.cd012657
2. Biologics or tofacitinib for people with rheumatoid arthritis unsuccessfully treated with biologics: a systematic review and network meta-analysis.
   Singh JA, Hossain A, Tanjong Ghogomu E, Mudano AS, et al · · 2017 · cited 38× · PMID 28282491 · DOI 10.1002/14651858.cd012591
3. 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.
   MacIsaac KD, Baumgartner R, Kang J, Loboda A, et al · · 2014 · cited 21× · PMID 25504080 · DOI 10.1371/journal.pone.0113937
4. 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.
   Beals C, Baumgartner R, Peterfy C, Balanescu A, et al · · 2017 · cited 5× · PMID 29236711 · DOI 10.1371/journal.pone.0187397
5. Quantitative AI based on evolutionary computation and information theory combined with mathematical functions yields algorithmic RNA biomarkers from a randomized rheumatoid arthritis clinical trial, accurately predicting individual patient responses to anti-TNF treatment, to enab
   Horgan K, McDermott MF, Harrington D, Simonyan V, et al · · 2024 · DOI 10.1101/2024.01.29.24301910