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)

Rheumatoid Arthritis Clinical Trial

— MUSICA  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01185288
• Other study ID #: M12-071
• Status: Completed
• Phase: Phase 4
• First received: August 18, 2010
• Last updated: January 31, 2014
• Start date: September 2010
• Est. completion date: January 2013

Study information

• Verified date: January 2014
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 309
• Est. completion date: January 2013
• Est. primary completion date: January 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

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

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Biological:
• Adalimumab
Adalimumab in pre-filled syringes

Drug:
• Methotrexate
Methotrexate capsule

Locations

Country	Name	City	State
Puerto Rico	Site Reference ID/Investigator# 38691	San Juan
Puerto Rico	Site Reference ID/Investigator# 60850	San Juan
Puerto Rico	Site Reference ID/Investigator# 60851	Vega Baja
United States	Site Reference ID/Investigator# 38263	Asheville	North Carolina
United States	Site Reference ID/Investigator# 38202	Bend	Oregon
United States	Site Reference ID/Investigator# 38981	Bowling Green	Kentucky
United States	Site Reference ID/Investigator# 38983	Bronx	New York
United States	Site Reference ID/Investigator# 40124	Clifton	New Jersey
United States	Site Reference ID/Investigator# 38086	Covington	Louisiana
United States	Site Reference ID/Investigator# 37980	Dallas	Texas
United States	Site Reference ID/Investigator# 44888	Dallas	Texas
United States	Site Reference ID/Investigator# 43049	Danbury	Connecticut
United States	Site Reference ID/Investigator# 38265	Duncansville	Pennsylvania
United States	Site Reference ID/Investigator# 39023	Eugene	Oregon
United States	Site Reference ID/Investigator# 40125	Fall River	Massachusetts
United States	Site Reference ID/Investigator# 38087	Franklin	Wisconsin
United States	Site Reference ID/Investigator# 38978	Freehold	New Jersey
United States	Site Reference ID/Investigator# 38261	Greenville	North Carolina
United States	Site Reference ID/Investigator# 37981	Hemet	California
United States	Site Reference ID/Investigator# 43050	Houston	Texas
United States	Site Reference ID/Investigator# 38982	Huntsville	Alabama
United States	Site Reference ID/Investigator# 38082	Jackson	Tennessee
United States	Site Reference ID/Investigator# 38687	Jacksonville	Florida
United States	Site Reference ID/Investigator# 65490	Las Vegas	Nevada
United States	Site Reference ID/Investigator# 38688	Lawrenceville	Georgia
United States	Site Reference ID/Investigator# 44823	Little Rock	Arkansas
United States	Site Reference ID/Investigator# 40208	Long Beach	California
United States	Site Reference ID/Investigator# 39024	Mayfield Village	Ohio
United States	Site Reference ID/Investigator# 38689	Meridian	Idaho
United States	Site Reference ID/Investigator# 42044	Mesa	Arizona
United States	Site Reference ID/Investigator# 40105	Miami	Florida
United States	Site Reference ID/Investigator# 40127	Oklahoma City	Oklahoma
United States	Site Reference ID/Investigator# 37983	Phoenix	Arizona
United States	Site Reference ID/Investigator# 44344	Richmond	Virginia
United States	Site Reference ID/Investigator# 38085	Rock Island	Illinois
United States	Site Reference ID/Investigator# 38423	Sacramento	California
United States	Site Reference ID/Investigator# 43735	San Antonio	Texas
United States	Site Reference ID/Investigator# 38083	Sarasota	Florida
United States	Site Reference ID/Investigator# 38084	Seattle	Washington
United States	Site Reference ID/Investigator# 38542	Seattle	Washington
United States	Site Reference ID/Investigator# 40210	Seattle	Washington
United States	Site Reference ID/Investigator# 38264	Smithtown	New York
United States	Site Reference ID/Investigator# 38424	Spokane	Washington
United States	Site Reference ID/Investigator# 40128	Springfield	Illinois
United States	Site Reference ID/Investigator# 38203	Tacoma	Washington
United States	Site Reference ID/Investigator# 38686	Tuscaloosa	Alabama
United States	Site Reference ID/Investigator# 38204	Victorville	California
United States	Site Reference ID/Investigator# 40123	Voorhees	New Jersey
United States	Site Reference ID/Investigator# 40762	Walnut Creek	California

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie (prior sponsor, Abbott)

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Serum Adalimumab Trough Concentrations at Week 24	Serum trough concentrations of adalimumab assessed at week 24 (24 weeks after the 1st dose).	Week 24	No
Primary	Disease Activity Score for 28 Joints Based on C-reactive Protein (DAS28[CRP]) at 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	No
Secondary	Percentage of Participants With Power Doppler Ultrasound (PD U/S) Score for Synovial Vascularity Improvement by 30% at Week 24	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	No
Secondary	Percentage of Participants With American College of Rheumatology 50% (ACR50) Criteria Response at Week 24	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	No
Secondary	Percentage of Participants With American College of Rheumatology 70% (ACR70) Criteria Response at Week 24	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	No
Secondary	Percentage of Participants With a Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) = -0.22 at Week 24	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	No
Secondary	Percent Change From Baseline in Medical Outcomes Study Version II (MOS) Sleep Problem Index 9 at Week 24	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	No

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