A Study to Determine the Effect of Methotrexate (MTX) Dose on Clinical Outcome and Ultrasonographic Signs in Subjects With Moderately to Severely Active Rheumatoid Arthritis (RA) Treated With Adalimumab (MUSICA) (MUSICA)

January 31, 2014 updated by: AbbVie (prior sponsor, Abbott)

A Multicenter, Double-Blind, Randomized, Parallel-Arm Study to Determine the Effect of Methotrexate Dose on Clinical Outcome and Ultrasonographic Signs in Subjects With Moderately to Severely Active Rheumatoid Arthritis Treated With Adalimumab (MUSICA)

This study will investigate the efficacy of both low and high doses of methotrexate (MTX) in combination with open-label adalimumab (ADA) in patients who have had an inadequate response to high dose of MTX. The study will also evaluate the pharmacokinetics and safety of the two regimens of MTX in combination with ADA in participants with rheumatoid arthritis (RA).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

309

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Puerto Rico
      • San Juan, Puerto Rico, 00936-5067
        • Site Reference ID/Investigator# 60850
      • San Juan, Puerto Rico, 00936-8344
        • Site Reference ID/Investigator# 38691
      • Vega Baja, Puerto Rico, 00694-0764
        • Site Reference ID/Investigator# 60851
  • United States
    • Alabama
      • Huntsville, Alabama, United States, 35801
        • Site Reference ID/Investigator# 38982
      • Tuscaloosa, Alabama, United States, 35406
        • Site Reference ID/Investigator# 38686
    • Arizona
      • Mesa, Arizona, United States, 85202
        • Site Reference ID/Investigator# 42044
      • Phoenix, Arizona, United States, 85031
        • Site Reference ID/Investigator# 37983
    • Arkansas
      • Little Rock, Arkansas, United States, 72205
        • Site Reference ID/Investigator# 44823
    • California
      • Hemet, California, United States, 92543
        • Site Reference ID/Investigator# 37981
      • Long Beach, California, United States, 90822
        • Site Reference ID/Investigator# 40208
      • Sacramento, California, United States, 95816
        • Site Reference ID/Investigator# 38423
      • Victorville, California, United States, 92395
        • Site Reference ID/Investigator# 38204
      • Walnut Creek, California, United States, 94598
        • Site Reference ID/Investigator# 40762
    • Connecticut
      • Danbury, Connecticut, United States, 06810
        • Site Reference ID/Investigator# 43049
    • Florida
      • Jacksonville, Florida, United States, 32209
        • Site Reference ID/Investigator# 38687
      • Miami, Florida, United States, 33169
        • Site Reference ID/Investigator# 40105
      • Sarasota, Florida, United States, 34239
        • Site Reference ID/Investigator# 38083
    • Georgia
      • Lawrenceville, Georgia, United States, 30045
        • Site Reference ID/Investigator# 38688
    • Idaho
      • Meridian, Idaho, United States, 83642
        • Site Reference ID/Investigator# 38689
    • Illinois
      • Rock Island, Illinois, United States, 61201
        • Site Reference ID/Investigator# 38085
      • Springfield, Illinois, United States, 62704
        • Site Reference ID/Investigator# 40128
    • Kentucky
      • Bowling Green, Kentucky, United States, 42101
        • Site Reference ID/Investigator# 38981
    • Louisiana
      • Covington, Louisiana, United States, 70433
        • Site Reference ID/Investigator# 38086
    • Massachusetts
      • Fall River, Massachusetts, United States, 02720
        • Site Reference ID/Investigator# 40125
    • Nevada
      • Las Vegas, Nevada, United States, 89102
        • Site Reference ID/Investigator# 65490
    • New Jersey
      • Clifton, New Jersey, United States, 07012
        • Site Reference ID/Investigator# 40124
      • Freehold, New Jersey, United States, 07728
        • Site Reference ID/Investigator# 38978
      • Voorhees, New Jersey, United States, 08043
        • Site Reference ID/Investigator# 40123
    • New York
      • Bronx, New York, United States, 10467
        • Site Reference ID/Investigator# 38983
      • Smithtown, New York, United States, 11787
        • Site Reference ID/Investigator# 38264
    • North Carolina
      • Asheville, North Carolina, United States, 28803
        • Site Reference ID/Investigator# 38263
      • Greenville, North Carolina, United States, 27834
        • Site Reference ID/Investigator# 38261
    • Ohio
      • Mayfield Village, Ohio, United States, 44143
        • Site Reference ID/Investigator# 39024
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Site Reference ID/Investigator# 40127
    • Oregon
      • Bend, Oregon, United States, 97701
        • Site Reference ID/Investigator# 38202
      • Eugene, Oregon, United States, 97401
        • Site Reference ID/Investigator# 39023
    • Pennsylvania
      • Duncansville, Pennsylvania, United States, 16635
        • Site Reference ID/Investigator# 38265
    • Tennessee
      • Jackson, Tennessee, United States, 38305
        • Site Reference ID/Investigator# 38082
    • Texas
      • Dallas, Texas, United States, 75231
        • Site Reference ID/Investigator# 37980
      • Dallas, Texas, United States, 75246
        • Site Reference ID/Investigator# 44888
      • Houston, Texas, United States, 77074
        • Site Reference ID/Investigator# 43050
      • San Antonio, Texas, United States, 78229
        • Site Reference ID/Investigator# 43735
    • Virginia
      • Richmond, Virginia, United States, 23294
        • Site Reference ID/Investigator# 44344
    • Washington
      • Seattle, Washington, United States, 98101
        • Site Reference ID/Investigator# 40210
      • Seattle, Washington, United States, 98122
        • Site Reference ID/Investigator# 38084
      • Seattle, Washington, United States, 98133
        • Site Reference ID/Investigator# 38542
      • Spokane, Washington, United States, 99204
        • Site Reference ID/Investigator# 38424
      • Tacoma, Washington, United States, 98405
        • Site Reference ID/Investigator# 38203
    • Wisconsin
      • Franklin, Wisconsin, United States, 53132
        • Site Reference ID/Investigator# 38087

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Adult subjects with moderately to severely active rheumatoid arthritis
  • Subjects must have a DAS28(CRP) (Disease Activity Score using C-Reactive Protein) greater than or equal to 3.2 at baseline (there is no minimum CRP score required to qualify)
  • Subjects must have at least 5/68 tender joints plus 5/66 swollen joints assessed at screening or baseline
  • Subject must treated with and MTX (methotrexate) dose (oral and/or injectable) of 15 mg or more per week (no upper limit on dose) for at least 12 weeks prior to screening
  • Subject is either biologic-naïve or has only one prior biologic disease-modifying antirheumatic drug (i.e. abatacept, anakinra, certolizumab, etanercept, golimumab, infliximab, or tocilizumab)

Exclusion Criteria:

  • Previous exposure to adalimumab (Humira), rituximab (Rituxan), natalizumab (Tysabri), efalizumab (Raptiva)
  • Subject has been treated with intra-articular or parenteral administration of corticosteroids within 4 weeks of screening
  • Subject has diagnosis or history of gout or pseudogout
  • Subject has undergone joint surgery within 12 weeks of screening (at joints to be assessed by ultrasound)
  • Subject has history of chronic arthritis diagnosed before age 16 years

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Adalimumab + Low Dose Methotrexate
Open-label adalimumab (40 mg subcutaneous every other week) plus blinded, low dose methotrexate (7.5 mg orally once weekly).
Biological: Adalimumab
Adalimumab in pre-filled syringes
Other Names:
  • ABT-D2E7
  • Humira
Drug: Methotrexate
Methotrexate capsule
Active Comparator: Adalimumab + High Dose Methotrexate
Open-label adalimumab (40 mg subcutaneous every other week) plus blinded, high dose methotrexate (20 mg orally once weekly).
Biological: Adalimumab
Adalimumab in pre-filled syringes
Other Names:
  • ABT-D2E7
  • Humira
Drug: Methotrexate
Methotrexate capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease Activity Score for 28 Joints Based on C-reactive Protein (DAS28[CRP]) at Week 24
Time Frame: Week 24
The DAS28(CRP) score includes 28 tender joint counts, 28 swollen joint counts, C-reactive protein, and participant's global assessment of disease activity. Scores on the DAS28(CRP) range from 0 to 10. A DAS28(CRP) score ≥ 5.1 indicates high disease activity, and a DAS28(CRP) score < 2.6 indicates clinical remission. Least squares means and 95% CI were from 2-way ANCOVA model with effects for baseline DAS28(CRP) value, treatment group, and prior methotrexate dose group.
Week 24

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Power Doppler Ultrasound (PD U/S) Score for Synovial Vascularity Improvement by 30% at Week 24
Time Frame: Baseline, 24 weeks
PD U/S assessed the severity of synovial inflammation in both hands (bilateral wrists, metacarpophalangeal joints 2, 3, 5, and metatarsophalangeal joint 5). Bilateral images based on dorsal midline imaging of the wrist, dorsal and volar imaging of metacarpophalangeal joints, and dorsal imaging alone of metatarsophalangeal joints are scored using a 4-grade scale: grade 0 or normal = normal joint (no Doppler signal); grade 1 or mild = mild synovitis (≤ 3 isolated signals); grade 2 or moderate = moderate synovitis (> 3 isolated signals or a confluent signal in < 50% of synovial area); grade 3 or marked = marked synovitis (signals in ≥ 50% of the synovial area). Each image is rated 0 to 3, for a total possible score ranging from 0 to 48 (16*0, 16*3) for 2 hands. Higher grade/score=more severe disease. Change = week 24 score - baseline score.
Baseline, 24 weeks
Percentage of Participants With American College of Rheumatology 50% (ACR50) Criteria Response at Week 24
Time Frame: Baseline, 24 weeks
Response, as defined by ACR50 criteria at week 24. A participant is a responder if the following 3 criteria for improvement from baseline are met: ≥ 50% improvement in tender joint count; ≥ 50% improvement in swollen joint count; and ≥ 50% improvement in at least 3 of the 5 following parameters: physician global assessment of disease activity, participant global assessment of disease activity, participant assessment of pain, disability index of the health assessment questionnaire, and acute phase reactant value (C-reactive protein).
Baseline, 24 weeks
Percentage of Participants With American College of Rheumatology 70% (ACR70) Criteria Response at Week 24
Time Frame: Baseline, 24 weeks
Response, as defined by ACR70 criteria at week 24. A participant is a responder if the following 3 criteria for improvement from baseline are met: ≥ 70% improvement in tender joint count; ≥ 70% improvement in swollen joint count; and ≥ 70% improvement in at least 3 of the 5 following parameters: physician global assessment of disease activity, participant global assessment of disease activity, participant assessment of pain, disability index of the health assessment questionnaire, and acute phase reactant value (C-reactive protein).
Baseline, 24 weeks
Percentage of Participants With a Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) ≤ -0.22 at Week 24
Time Frame: Baseline, 24 weeks
The HAQ-DI is a patient-reported questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0), with some difficulty (1), with much difficulty (2), and unable to do (3). Scores on each task were summed and averaged to provide an overall score ranging from 0 (no disability) to 3 (very severe, high dependency disability). The minimal clinically important difference (MCID) defined for the HAQ-DI is a change from baseline of ≤ -0.22. Normal physical function is defined by HAQ-DI score of < 0.5. Negative change from baseline in the overall score indicates improvement.
Baseline, 24 weeks
Percent Change From Baseline in Medical Outcomes Study Version II (MOS) Sleep Problem Index 9 at Week 24
Time Frame: Baseline, 24 weeks
The least squares mean percentage change in MOS Sleep Problem Index 9 from baseline to week 24. The MOS Sleep Problem Index 9 consists of 9 questions to assess sleep, including how long it takes the participant to fall asleep (1=0 to 15 minutes, to 5=more than 60 minutes); and aspects of related to quality of sleep, including how often the participant felt that the sleep was not quiet, felt rested upon waking, awakened short of breath or with a headache, felt drowsy during the day, had trouble falling sleep, how often were awaken, had trouble staying awake during the day, and got needed amount of sleep (1=all the time; 5=none of the time). Least squares means and 95% CI were from 2-way ANCOVA model with effects for baseline MOS Sleep Problem Index value, treatment group, and prior methotrexate dose group.
Baseline, 24 weeks

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Serum Adalimumab Trough Concentrations at Week 24
Time Frame: Week 24
Serum trough concentrations of adalimumab assessed at week 24 (24 weeks after the 1st dose).
Week 24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AbbVie (prior sponsor, Abbott)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2010

Primary Completion (Actual)

January 1, 2013

Study Completion (Actual)

January 1, 2013

Study Registration Dates

First Submitted

August 18, 2010

First Submitted That Met QC Criteria

August 18, 2010

First Posted (Estimate)

August 19, 2010

Study Record Updates

Last Update Posted (Estimate)

March 18, 2014

Last Update Submitted That Met QC Criteria

January 31, 2014

Last Verified

January 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • M12-071

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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