AzTrials
AzTrials

Arthritis, RheumatoidPhase 2NCT01313520

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)

A Phase 2 study testing Infliximab in people with Arthritis, Rheumatoid, run by Merck Sharp & Dohme LLC.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Arthritis, Rheumatoid
What is being tested?
Infliximab
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
61 participants
Where
No sites listed yet
Study dates
1 Mar 2011to 1 Mar 2012
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 13Show fewer
  • 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

Who cannot join

  • 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
Show all 15Show fewer
  • 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

About this study

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)

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.

Being tested
Infliximab, Placebo
Medical subject headings
Arthritis, Rheumatoid

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • InfliximabDrug

    Also called SCH 215596, Remicade

    3 mg/kg of Infliximab at Weeks 0, 2, 6, 14 via intravenous infusion

  • PlaceboDrug

    250 mL of 0.9% sodium chloride at Weeks 0, 2, 6, 14 via intravenous infusion

Study groups in NCT01313520
Study groupRoleWhat they receive
InfliximabExperimental3 mg/kg of Infliximab intravenous infusion
Receives: Drug: Infliximab
PlaceboPlacebo comparatorsaline via intravenous infusion
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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).

    Measured: Baseline and week 14

Secondary outcomes (4)

  1. 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).

    Measured: Baseline and week 14

  2. 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.

    Measured: Baseline and week 14

  3. 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.

    Measured: Baseline and Week 14

  4. 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.

    Measured: Baseline and Week 14

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Mar 2011 (estimated)
  2. Study start1 Mar 2011
  3. Primary completion1 Mar 2012
  4. Study completion1 Mar 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
61 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01313520
Sponsor's protocol ID
P08136
Other IDs
2011-000079-14
Status last verified
Apr 2017
First submitted
25 Feb 2011
Last updated
10 May 2017
Data monitoring committee
No
Individual data sharing
Yes: 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

Publications

  • 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.

    PubMed 29236711

  • 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.

    PubMed 25504080

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Infliximab in people with Arthritis, Rheumatoid, run by Merck Sharp & Dohme LLC.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 May 2017. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 Jul 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in the Volume Transfer Rate From the Blood Plasma to the Enhancing Synovium (Ktrans) (time frame: Baseline and week 14). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01313520, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 May 2017.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in