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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)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier:
NCT01185288
First received: August 18, 2010
Last updated: January 31, 2014
Last verified: January 2014
  Purpose

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).


Condition Intervention Phase
Rheumatoid Arthritis
Biological: Adalimumab
Drug: Methotrexate
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by AbbVie:

Primary Outcome Measures:
  • Disease Activity Score for 28 Joints Based on C-reactive Protein (DAS28[CRP]) at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With American College of Rheumatology 50% (ACR50) Criteria Response at Week 24 [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: No ]
    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).

  • Percentage of Participants With American College of Rheumatology 70% (ACR70) Criteria Response at Week 24 [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: No ]
    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).

  • 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 ] [ Designated as safety issue: No ]
    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.

  • Percent Change From Baseline in Medical Outcomes Study Version II (MOS) Sleep Problem Index 9 at Week 24 [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: No ]
    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.


Other Outcome Measures:
  • Serum Adalimumab Trough Concentrations at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    Serum trough concentrations of adalimumab assessed at week 24 (24 weeks after the 1st dose).


Enrollment: 309
Study Start Date: September 2010
Study Completion Date: January 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01185288

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

Additional Information:
No publications provided

Responsible Party: AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier: NCT01185288     History of Changes
Other Study ID Numbers: M12-071
Study First Received: August 18, 2010
Results First Received: January 31, 2014
Last Updated: January 31, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by AbbVie:
Rheumatoid Arthritis

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Autoimmune Diseases
Connective Tissue Diseases
Immune System Diseases
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Adalimumab
Methotrexate
Abortifacient Agents
Abortifacient Agents, Nonsteroidal
Anti-Inflammatory Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antirheumatic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014