Clinical trial NCT00195702: Efficacy and Safety of Adalimumab in Patients With Active Rheumatoid Arthritis Treated Concomitantly With Methotrexate.
Official title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of the Human Anti-TNF Monoclonal Antibody Adalimumab in Rheumatoid Arthritis Patients Currently Receiving Treatment With Methotrexate
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Keywords: Rheumatoid Arthritis
Lead sponsor: Abbott
Sponsor class: INDUSTRY
First posted: 2005-09-20
Enrollment: 619
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of the study was to assess the safety, immunogenicity, and clinical efficacy of adalimumab compared with placebo (during double-blind phase) and to to evaluate the long-term safety and maintenance of efficacy following repeated administration of adalimumab (during open-label extension phase) in patients with persistently active rheumatoid arthritis who were receiving concurrent methotrexate therapy.

Detailed description: This was a 10-year study which had an initial 52-week, double-blind, placebo-controlled phase followed by an open-label extension phase up to 9 years in duration. Data were analyzed for the double-blind phase using all patients who were randomized and received at least one dose of study drug through Week 52 and for all patients who received at least one dose of adalimumab during the 10-year study (the Intent-to-Treat \[ITT\] population).

Eligibility criteria: Inclusion Criteria:

* Age 18 or older and in good health (Investigator discretion) with a recent stable medical history
* Met American College of Rheumatology (ACR) criteria for diagnosis of active rheumatoid arthritis (RA) and had at both screening and baseline visits \>=6 swollen joints and \>=9 tender joints, despite a minimum of 3-months treatment with methotrexate (MTX). (Distal interphalangeal joints \[DIPs\] were not to be included in joint count for inclusion. The screening and baseline visits could be 3 to 28 days apart for patients not previously receiving disease-modifying anti-rheumatic drugs \[DMARDs\] other than MTX or 4 to 6 weeks for patients requiring a DMARD washout period.)
* Insufficient efficacy with MTX 12.5 to 25 mg per week (10 mg per week if MTX intolerant).
* If patient on a second-line treatment (DMARD) other than MTX, he/she had to discontinue it for at least 28 days before the baseline visit (the washout period).
* Treatment with oral folic acid 1-3 mg/day or, if appropriate, up to 10 mg leucovorin per week.
* Both rheumatoid factor positivity and a C-reactive protein value \>=1 mg/dL, or at least one joint erosion on X-ray.

Exclusion Criteria:

* Subject considered by the investigator, for any reason, to be an unsuitable candidate for the study.
* Female subject who was pregnant or breast-feeding or considering becoming pregnant.
* Preceding treatment with any tumor necrosis factor (TNF) antagonist, including adalimumab.
* Prior exposure to alkylating agents, such as chlorambucil or cyclophosphamide.
* Intra-articular, intramuscular, or intravenous administration of corticosteroids within 4 weeks prior to the screening visit.
* Subject was wheelchair bound or bedridden.

Primary outcomes:
measure: Number of Participants Meeting American College of Rheumatology 20% (ACR20) Response Criteria at Week 24
timeFrame: Week 24
measure: Change From Baseline in Modified Total Sharp X-ray Score at Week 52
timeFrame: Baseline and Week 52
measure: Change From Baseline in the Disability Index of the Health Assessment Questionnaire (HAQ) at Week 52
timeFrame: Baseline and Week 52
Secondary outcomes:
measure: Number of Participants Meeting ACR20 Response Criteria at Week 52
timeFrame: Week 52
measure: Change From Baseline in Modified Total Sharp X-ray Score at Week 24
timeFrame: Baseline and Week 24
measure: Change From Baseline in the Disability Index of the Health Assessment Questionnaire (HAQ) at Week 24
timeFrame: Baseline and Week 24
measure: Maintenance of the Disability Index of the HAQ at Week 52 for Participants Who Were Responders at Week 12 or Week 24
timeFrame: Week 52
measure: Maintenance of ACR20 Response at Week 52 for Participants Who Were ACR20 Responders at Week 24
timeFrame: Week 52
measure: Number of Participants With a Continuous ACR70 Response for 6 Months During 52 Weeks of Treatment
timeFrame: Baseline through Week 52
measure: Time to First Response According to ACR20 Criteria - Number of Participants Meeting ACR20 Criteria for the First Time at Each Time Point
timeFrame: Baseline through Week 52
measure: Time to First Response According to ACR50 Criteria - Number of Participants Meeting ACR50 Criteria for the First Time at Each Time Point
timeFrame: Baseline through Week 52
measure: Time to First Response According to ACR70 Criteria - Number of Participants Meeting ACR70 Criteria for the First Time at Each Time Point
timeFrame: Baseline through Week 52
measure: Estimated Yearly Progression of Rheumatoid Arthritis
timeFrame: Baseline and Week 52
Other outcomes:
measure: Baseline Measure: Gender - Female/Male - for the Any Adalimumab Through Year 10 Group (Intent-to-Treat)
timeFrame: Baseline for Intent-to-Treat (Any Adalimumab Through Year 10) Group
measure: Baseline Measure: Age Categories for the Any Adalimumab Through Year 10 Group (Intent-to-Treat)
timeFrame: Baseline for Intent-to-Treat (Any Adalimumab Through Year 10) Group
measure: Number of Participants Meeting American College of Rheumatology 20% (ACR20) Response Criteria at Week 260
timeFrame: Week 260
measure: Number of Participants Meeting the American College of Rheumatology 20% (ACR20) Response Criteria at Week 520
timeFrame: Week 520
measure: Number of Participants Meeting American College of Rheumatology 50% (ACR50) Response Criteria at Week 260
timeFrame: Week 260
measure: Number of Participants Meeting the American College of Rheumatology 50% (ACR50) Response Criteria at Week 520
timeFrame: Week 520
measure: Number of Participants Meeting the American College of Rheumatology 70% (ACR70) Response Criteria at Week 260
timeFrame: Week 260
measure: Number of Participants Meeting the American College of Rheumatology 70% (ACR70) Response Criteria at Week 520
timeFrame: Week 520
measure: Number of Participants With a Continuous American College of Rheumatology 70% (ACR70) Response for at Least 6 Months Through Year 10
timeFrame: Baseline through Week 520
measure: Number of Participants With at Least a 0.22 Reduction From Baseline in the Health Assessment Questionnaire (HAQ) Disability Index at Week 260
timeFrame: Week 260
measure: Number of Participants With at Least a 0.22 Reduction From Baseline in the Health Assessment Questionnaire (HAQ) Disability Index at Week 520
timeFrame: Week 520
measure: Change From Baseline in the Disability Index of the Health Assessment Questionnaire (HAQ) at Week 260
timeFrame: Baseline and Week 260
measure: Change From Baseline in the Disability Index of the Health Assessment Questionnaire (HAQ) at Week 520
timeFrame: Baseline and Week 520
measure: Change From Baseline in Modified Total Sharp X-ray Score at Week 416
timeFrame: Baseline and Week 416
measure: Change From Baseline in Modified Total Sharp X-ray Score at Week 520
timeFrame: Baseline and Week 520
Locations:
city: Huntsville
country: United States
facility: Site Ref # / Investigator 424
state: Alabama
city: Mobile
country: United States
facility: Site Ref # / Investigator 2510
state: Alabama
city: Phoenix
country: United States
facility: Site Ref # / Investigator 60729
state: Arizona
city: Scottsdale
country: United States
facility: Site Ref # / Investigator 725
state: Arizona
city: Anaheim
country: United States
facility: Site Ref # / Investigator 60736
state: California
city: Escondido
country: United States
facility: Site Ref # / Investigator 360
state: California
city: La Jolla
country: United States
facility: Site Ref # / Investigator 714
state: California
city: La Jolla
country: United States
facility: Site Ref # / Investigator 469
state: California
city: Palm Desert
country: United States
facility: Site Ref # / Investigator 419
state: California
city: San Jose
country: United States
facility: Site Ref # / Investigator 492
state: California
city: San Louis Obispo
country: United States
facility: Site Ref # / Investigator 60734
state: California
city: Van Nuys
country: United States
facility: Site Ref # / Investigator 60739
state: California
city: Danbury
country: United States
facility: Site Ref # / Investigator 712
state: Connecticut
city: Aventura
country: United States
facility: Site Ref # / Investigator 710
state: Florida
city: Dunedin
country: United States
facility: Site Ref # / Investigator 498
state: Florida
city: Orlando
country: United States
facility: Site Ref # / Investigator 499
state: Florida
city: Tampa
country: United States
facility: Site Ref # / Investigator 729
state: Florida
city: Zephyrhills
country: United States
facility: Site Ref # / Investigator 463
state: Florida
city: Boise
country: United States
facility: Site Ref # / Investigator 2436
state: Idaho
city: Idaho Falls
country: United States
facility: Site Ref # / Investigator 485
state: Idaho
city: Chicago
country: United States
facility: Site Ref # / Investigator 60732
state: Illinois
city: Springfield
country: United States
facility: Site Ref # / Investigator 726
state: Illinois
city: Indianapolis
country: United States
facility: Site Ref # / Investigator 2506
state: Indiana
city: South Bend
country: United States
facility: Site Ref # / Investigator 732
state: Indiana
city: Shawnee Mission
country: United States
facility: Site Ref # / Investigator 60730
state: Kansas
city: Wichita
country: United States
facility: Site Ref # / Investigator 467
state: Kansas
city: Wichita
country: United States
facility: Site Ref # / Investigator 494
state: Kansas
city: Lexington
country: United States
facility: Site Ref # / Investigator 491
state: Kentucky
city: Portland
country: United States
facility: Site Ref # / Investigator 2508
state: Maine
city: Baltimore
country: United States
facility: Site Ref # / Investigator 392
state: Maryland
city: Cumberland
country: United States
facility: Site Ref # / Investigator 354
state: Maryland
city: Wheaton
country: United States
facility: Site Ref # / Investigator 730
state: Maryland
city: Burlington
country: United States
facility: Site Ref # / Investigator 465
state: Massachusetts
city: Worcester
country: United States
facility: Site Ref # / Investigator 2512
state: Massachusetts
city: Grand Rapids
country: United States
facility: Site Ref # / Investigator 471
state: Michigan
city: Kalamazoo
country: United States
facility: Site Ref # / Investigator 473
state: Michigan
city: Kansas City
country: United States
facility: Site Ref # / Investigator 731
state: Missouri
city: St. Louis
country: United States
facility: Site Ref # / Investigator 502
state: Missouri
city: St. Louis
country: United States
facility: Site Ref # / Investigator 482
state: Missouri
city: St. Louis
country: United States
facility: Site Ref # / Investigator 371
state: Missouri
city: Omaha
country: United States
facility: Site Ref # / Investigator 487
state: Nebraska
city: Concord
country: United States
facility: Site Ref # / Investigator 353
state: New Hampshire
city: Dover
country: United States
facility: Site Ref # / Investigator 364
state: New Hampshire
city: Mercerville
country: United States
facility: Site Ref # / Investigator 60726
state: New Jersey
city: Voorhees
country: United States
facility: Site Ref # / Investigator 358
state: New Jersey
city: Rochester
country: United States
facility: Site Ref # / Investigator 483
state: New York
city: Durham
country: United States
facility: Site Ref # / Investigator 512
state: North Carolina
city: Greensboro
country: United States
facility: Site Ref # / Investigator 340
state: North Carolina
city: Raleigh
country: United States
facility: Site Ref # / Investigator 461
state: North Carolina
city: Raleigh
country: United States
facility: Site Ref # / Investigator 500
state: North Carolina
city: Raleigh
country: United States
facility: Site Ref # / Investigator 60731
state: North Carolina
city: Salisbury
country: United States
facility: Site Ref # / Investigator 60737
state: North Carolina
city: Mayfield Village
country: United States
facility: Site Ref # / Investigator 456
state: Ohio
city: Oklahoma City
country: United States
facility: Site Ref # / Investigator 470
state: Oklahoma
city: Oklahoma
country: United States
facility: Site Ref # / Investigator 60723
state: Oklahoma
city: Eugene
country: United States
facility: Site Ref # / Investigator 422
state: Oregon
city: Colmar
country: United States
facility: Site Ref # / Investigator 60735
state: Pennsylvania
city: Duncansville
country: United States
facility: Site Ref # / Investigator 2507
state: Pennsylvania
city: East Norriton
country: United States
facility: Site Ref # / Investigator 717
state: Pennsylvania
city: Mechanicsburg
country: United States
facility: Site Ref # / Investigator 352
state: Pennsylvania
city: Wexford
country: United States
facility: Site Ref # / Investigator 480
state: Pennsylvania
city: Wyomissing
country: United States
facility: Site Ref # / Investigator 2511
state: Pennsylvania
city: Wyomissing
country: United States
facility: Site Ref # / Investigator 60724
state: Pennsylvania
city: Charleston
country: United States
facility: Site Ref # / Investigator 718
state: South Carolina
city: Memphis
country: United States
facility: Site Ref # / Investigator 460
state: Tennessee
city: Nashville
country: United States
facility: Site Ref # / Investigator 462
state: Tennessee
city: Austin
country: United States
facility: Site Ref # / Investigator 716
state: Texas
city: Galveston
country: United States
facility: Site Ref # / Investigator 60728
state: Texas
city: Houston
country: United States
facility: Site Ref # / Investigator 2509
state: Texas
city: Houston
country: United States
facility: Site Ref # / Investigator 510
state: Texas
city: Falls Church
country: United States
facility: Site Ref # / Investigator 60725
state: Virginia
city: Richmond
country: United States
facility: Site Ref # / Investigator 711
state: Virginia
city: Seattle
country: United States
facility: Site Ref # / Investigator 509
state: Washington
city: Spokane
country: United States
facility: Site Ref # / Investigator 356
state: Washington
city: Tacoma
country: United States
facility: Site Ref # / Investigator 464
state: Washington
city: Kenosha
country: United States
facility: Site Ref # / Investigator 60738
state: Wisconsin
city: Calgary
country: Canada
facility: Site Ref # / Investigator 475
state: Alberta
city: Penticton
country: Canada
facility: Site Ref # / Investigator 495
state: British Columbia
city: Richmond
country: Canada
facility: Site Ref # / Investigator 2496
state: British Columbia
city: Winnipeg
country: Canada
facility: Site Ref # / Investigator 2495
state: Manitoba
city: Halifax
country: Canada
facility: Site Ref # / Investigator 496
state: Nova Scotia
city: Newmarket
country: Canada
facility: Site Ref # / Investigator 444
state: Ontario
city: Toronto
country: Canada
facility: Site Ref # / Investigator 2497
state: Ontario
city: Toronto
country: Canada
facility: Site Ref # / Investigator 478
state: Ontario
city: Toronto
country: Canada
facility: Site Ref # / Investigator 421
state: Ontario
city: Montreal
country: Canada
facility: Site Ref # / Investigator 363
state: Quebec
city: Saskatoon
country: Canada
facility: Site Ref # / Investigator 60702
state: Saskatchewan
Study officials:
affiliation: Abbott
name: Laura Redden, MD, PhD
role: STUDY_DIRECTOR
References:
citation: Smolen J, Fleischmann R, Aletaha D, Li Y, Zhou Y, Sainsbury I, Galindo IL. Disease activity improvements with optimal discriminatory ability between treatment arms: applicability in early and established rheumatoid arthritis clinical trials. Arthritis Res Ther. 2019 Nov 10;21(1):231. doi: 10.1186/s13075-019-2005-9.
citation: Keystone EC, Breedveld FC, van der Heijde D, van Vollenhoven RF, Emery P, Smolen JS, Sainsbury I, Florentinus S, Kupper H, Chen K, Kavanaugh A. Achieving comprehensive disease control in patients with early and established rheumatoid arthritis treated with adalimumab plus methotrexate versus methotrexate alone. RMD Open. 2017 Sep 26;3(2):e000445. doi: 10.1136/rmdopen-2017-000445. eCollection 2017.
citation: Burmester GR, Landewe R, Genovese MC, Friedman AW, Pfeifer ND, Varothai NA, Lacerda AP. Adalimumab long-term safety: infections, vaccination response and pregnancy outcomes in patients with rheumatoid arthritis. Ann Rheum Dis. 2017 Feb;76(2):414-417. doi: 10.1136/annrheumdis-2016-209322. Epub 2016 Jun 23.
citation: Emery P, Kavanaugh A, Bao Y, Ganguli A, Mulani P. Comprehensive disease control (CDC): what does achieving CDC mean for patients with rheumatoid arthritis? Ann Rheum Dis. 2015 Dec;74(12):2165-74. doi: 10.1136/annrheumdis-2014-205302. Epub 2014 Aug 19.
citation: Landewe R, Ostergaard M, Keystone EC, Florentinus S, Liu S, van der Heijde D. Analysis of integrated radiographic data from two long-term, open-label extension studies of adalimumab for the treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken). 2015 Feb;67(2):180-6. doi: 10.1002/acr.22426.
citation: Keystone EC, van der Heijde D, Kavanaugh A, Kupper H, Liu S, Guerette B, Mozaffarian N. Clinical, functional, and radiographic benefits of longterm adalimumab plus methotrexate: final 10-year data in longstanding rheumatoid arthritis. J Rheumatol. 2013 Sep;40(9):1487-97. doi: 10.3899/jrheum.120964. Epub 2013 Jul 1.
citation: Keystone EC, Kavanaugh A, Weinblatt ME, Patra K, Pangan AL. Clinical consequences of delayed addition of adalimumab to methotrexate therapy over 5 years in patients with rheumatoid arthritis. J Rheumatol. 2011 May;38(5):855-62. doi: 10.3899/jrheum.100752. Epub 2011 Feb 1.