Long Term Open Label Continuation Study

A Multi-Center Continuation Study of the Human Anti-TNF Antibody D2E7 Administered as a Subcutaneous Injection in Patients With Rheumatoid Arthritis

The purpose of the study was to assess the long-term safety and clinical efficacy following repeated administration of adalimumab in patients with rheumatoid arthritis.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Biological: Adalimumab

Detailed Description

Study DE020 was a multicenter, open-label continuation study for patients with rheumatoid arthritis who had participated in a prior Phase 1, 2, or 3 adalimumab study in the United States or Canada, had a favorable safety and efficacy profile when treated with adalimumab, and met the eligibility criteria for the continuation study. Participants received subcutaneous injections of adalimumab every other week (eow) or monthly based on the adalimumab regimen received in the prior study (i.e., participants who received monthly dosing in the prior study began the continuation study on monthly dosing; all other participants began adalimumab dosing at eow intervals). Participants who maintained an American College of Rheumatology 50% (ACR50) response for 2 consecutive visits could have their dosing interval lengthened to a monthly dosing schedule. Safety and efficacy data were collected over 520 weeks (10 years). Both safety and efficacy data were analyzed using all participants who received at least 1 dose of open-label adalimumab in the 10-year continuation study DE020 (the Full Analysis Set, n=846). Three patients who entered the continuation study but were never dosed were excluded from all analyses.

• Study Type: Interventional
• Enrollment (Actual): 846
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Calgary, Canada, T2V 1P9
    • Site Reference ID/Investigator# 513
  • Charlottetown, Canada, C1A 5Y8
    • Site Reference ID/Investigator# 568
  • Hamilton, Canada, L8N 1Y2
    • Site Reference ID/Investigator# 565
  • Hamilton, Canada, L8N 2B6
    • Site Reference ID/Investigator# 564
  • Kitchener, Canada, N2M 5N6
    • Site Reference ID/Investigator# 569
  • Montreal, Canada, H2L 1S6
    • Site Reference ID/Investigator# 3440
  • Montreal, Canada, H3Z 2Z3
    • Site Reference ID/Investigator# 413
  • North York, Canada, M3H 5Y8
    • Site Reference ID/Investigator# 66805
  • North York, Canada, M3H 5Y8
    • Site Reference ID/Investigator# 66807
  • Ottawa, Canada, K1H 7W9
    • Site Reference ID/Investigator# 414
  • Pointe-Claire, Canada, H9J 3W3
    • Site Reference ID/Investigator# 566
  • Sainte-Foy, Quebec, Canada, G1W 4R4
    • Site Reference ID/Investigator# 2467
  • Scarborough, Canada, M1B 4Y9
    • Site Reference ID/Investigator# 66804
  • St. John's, Canada, A1B 3E1
    • Site Reference ID/Investigator# 563
  • Toronto, Canada, M4N 3M5
    • Site Reference ID/Investigator# 2466
  • Toronto, Canada, M5L 3L9
    • Site Reference ID/Investigator# 567
  • Vancouver, Canada, V5Z 1L7
    • Site Reference ID/Investigator# 3442
  • Winnipeg, Canada, R3A 1M4
    • Site Reference ID/Investigator# 514
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • Site Reference ID/Investigator# 538
    • Birmingham, Alabama, United States, 35294-7201
      • Site Reference ID/Investigator# 4111
    • Mobile, Alabama, United States, 36608
      • Site Reference ID/Investigator# 4113
  • Alaska
    • Anchorage, Alaska, United States, 99508
      • Site Reference ID/Investigator# 408
  • Arizona
    • Tucson, Arizona, United States, 85710
      • Site Reference ID/Investigator# 537
  • California
    • Anaheim, California, United States, 92801
      • Site Reference ID/Investigator# 66822
    • La Jolla, California, United States, 92037-0943
      • Site Reference ID/Investigator# 557
    • Los Angeles, California, United States, 90048
      • Site Reference ID/Investigator# 387
    • Los Angeles, California, United States, 90095
      • Site Reference ID/Investigator# 555
    • Santa Barbara, California, United States, 93105
      • Site Reference ID/Investigator# 552
    • Santa Monica, California, United States, 90404
      • Site Reference ID/Investigator# 66864
    • Stanford, California, United States, 94305
      • Site Reference ID/Investigator# 535
    • Upland, California, United States, 91786
      • Site Reference ID/Investigator# 3412
    • Westlake Village, California, United States, 91361
      • Site Reference ID/Investigator# 451
  • Colorado
    • Colorado Springs, Colorado, United States, 80910
      • Site Reference ID/Investigator# 572
    • Denver, Colorado, United States, 80230
      • Site Reference ID/Investigator# 4109
  • Connecticut
    • Danbury, Connecticut, United States, 06810
      • Site Reference ID/Investigator# 541
    • Milford, Connecticut, United States, 06460
      • Site Reference ID/Investigator# 654
  • Delaware
    • Wilmington, Delaware, United States, 19808
      • Site Reference ID/Investigator# 655
  • Florida
    • Daytona Beach, Florida, United States, 32114
      • Site Reference ID/Investigator# 455
    • Fort Lauderdale, Florida, United States, 33334
      • Site Reference ID/Investigator# 431
    • Fort Myers, Florida, United States, 33901
      • Site Reference ID/Investigator# 574
    • Gainesville, Florida, United States, 32605
      • Site Reference ID/Investigator# 66843
    • Orlando, Florida, United States, 32804
      • Site Reference ID/Investigator# 579
    • Palm Harbor, Florida, United States, 34684
      • Site Reference ID/Investigator# 571
    • Sarasota, Florida, United States, 34239
      • Site Reference ID/Investigator# 651
    • St. Petersburg, Florida, United States, 33710
      • Site Reference ID/Investigator# 66863
    • Tampa, Florida, United States, 33609
      • Site Reference ID/Investigator# 542
    • Vero Beach, Florida, United States, 32962
      • Site Reference ID/Investigator# 415
    • Zephyrhills, Florida, United States, 33542
      • Site Reference ID/Investigator# 652
  • Idaho
    • Boise, Idaho, United States, 83702
      • Site Reference ID/Investigator# 449
    • Boise, Idaho, United States, 83706
      • Site Reference ID/Investigator# 4110
    • Coeur D'Alene, Idaho, United States, 83814
      • Site Reference ID/Investigator# 650
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Site Reference ID/Investigator# 578
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Site Reference ID/Investigator# 4112
  • Kentucky
    • Louisville, Kentucky, United States, 40291
      • Site Reference ID/Investigator# 547
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • Site Reference ID/Investigator# 534
  • Maryland
    • Chevy Chase, Maryland, United States, 20815
      • Site Reference ID/Investigator# 544
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Site Reference ID/Investigator# 653
    • Worcester, Massachusetts, United States, 01610
      • Site Reference ID/Investigator# 4114
  • Michigan
    • Petoskey, Michigan, United States, 49770
      • Site Reference ID/Investigator# 546
  • Missouri
    • St. Louis, Missouri, United States, 63128
      • Site Reference ID/Investigator# 577
  • Montana
    • Billings, Montana, United States, 59101
      • Site Reference ID/Investigator# 549
  • Nevada
    • Reno, Nevada, United States, 89502
      • Site Reference ID/Investigator# 561
  • New Jersey
    • Dover, New Jersey, United States, 07801
      • Site Reference ID/Investigator# 573
    • Toms River, New Jersey, United States, 08755
      • Site Reference ID/Investigator# 66842
    • Voorhees, New Jersey, United States, 08043
      • Site Reference ID/Investigator# 559
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Site Reference ID/Investigator# 562
  • New York
    • Brooklyn, New York, United States, 11203
      • Site Reference ID/Investigator# 66823
    • Lake Success, New York, United States, 11042
      • Site Reference ID/Investigator# 432
    • New York, New York, United States, 10003
      • Site Reference ID/Investigator# 657
    • New York, New York, United States, 10021
      • Site Reference ID/Investigator# 647
    • Port Jefferson Station, New York, United States, 11776
      • Site Reference ID/Investigator# 545
    • Syracuse, New York, United States, 13210
      • Site Reference ID/Investigator# 540
  • North Carolina
    • Statesville, North Carolina, United States, 28625
      • Site Reference ID/Investigator# 646
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Site Reference ID/Investigator# 438
    • Dayton, Ohio, United States, 45408
      • Site Reference ID/Investigator# 436
  • Oregon
    • Bend, Oregon, United States, 97701
      • Site Reference ID/Investigator# 548
    • Eugene, Oregon, United States, 97401
      • Site Reference ID/Investigator# 553
    • Portland, Oregon, United States, 97205
      • Site Reference ID/Investigator# 532
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18015
      • Site Reference ID/Investigator# 570
    • Ridley Park, Pennsylvania, United States, 19078-2210
      • Site Reference ID/Investigator# 575
    • Willow Grove, Pennsylvania, United States, 19090
      • Site Reference ID/Investigator# 585
  • Texas
    • Dallas, Texas, United States, 75231
      • Site Reference ID/Investigator# 2435
  • Virginia
    • Richmond, Virginia, United States, 23219
      • Site Reference ID/Investigator# 536
  • Washington
    • Everett, Washington, United States, 98201
      • Site Reference ID/Investigator# 649
    • Everett, Washington, United States, 98201
      • Site Reference ID/Investigator# 66862
    • Kirkland, Washington, United States, 98034
      • Site Reference ID/Investigator# 531
    • Olympia, Washington, United States, 98502
      • Site Reference ID/Investigator# 412
    • Spokane, Washington, United States, 99204
      • Site Reference ID/Investigator# 658
    • Vancouver, Washington, United States, 98664
      • Site Reference ID/Investigator# 576
    • Yakima, Washington, United States, 98902
      • Site Reference ID/Investigator# 551
  • Wisconsin
    • Glendale, Wisconsin, United States, 53217
      • Site Reference ID/Investigator# 656
    • Milwaukee, Wisconsin, United States, 53215
      • Site Reference ID/Investigator# 539

Participation Criteria

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

• Participant was in a prior D2E7 (adalimumab) study
• Participant was age 18 or older and in good health (Investigator discretion) with a recent stable medical history.

Exclusion Criteria

• Participant was considered by the investigator, for any reason, to be an unsuitable candidate for the study
• Participant was a female subject who is pregnant or breast-feeding or considering becoming pregnant
• Participant had any ongoing chronic or active infection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Adalimumab; Open-label adalimumab 40 mg	Biological: Adalimumab; Subcutaneous injection of 40 mg adalimumab every other week (eow) or monthly for up to 520 weeks (10 years); Other Names: Humira, ABT-D2E7

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Meeting American College of Rheumatology 20% (ACR20) Response Criteria at Week 520	ACR20 response criteria were: >=20% improvement in tender joint count; >=20% improvement in swollen joint count; and >=20% improvement in at least 3 of the 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and C-reactive protein (a laboratory marker of inflammation that is sensitive to acute changes in inflammatory response). All improvements were assessed relative to the baseline of the prior study.	Week 520
Number of Participants Meeting American College of Rheumatology 20% (ACR20) Response Criteria at Week 260	ACR20 response criteria were: >=20% improvement in tender joint count; >=20% improvement in swollen joint count; and >=20% improvement in at least 3 of the 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and C-reactive protein (a laboratory marker of inflammation that is sensitive to acute changes in inflammatory response). All improvements were assessed relative to the baseline of the prior study.	Week 260
Number of Participants Meeting American College of Rheumatology 50% (ACR50) Response Criteria at Week 520	ACR50 response criteria were: >=50% improvement in tender joint count; >=50% improvement in swollen joint count; and >=50% improvement in at least 3 of the 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and C-reactive protein (a laboratory marker of inflammation that is sensitive to acute changes in inflammatory response). All improvements were assessed relative to the baseline of the prior study.	Week 520
Number of Participants Meeting American College of Rheumatology 50% (ACR50) Response Criteria at Week 260	ACR50 response criteria were: >=50% improvement in tender joint count; >=50% improvement in swollen joint count; and >=50% improvement in at least 3 of the 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and C-reactive protein (a laboratory marker of inflammation that is sensitive to acute changes in inflammatory response). All improvements were assessed relative to the baseline of the prior study.	Week 260
Number of Participants Meeting American College of Rheumatology 70% (ACR70) Response Criteria at Week 520	ACR70 response criteria were: >=70% improvement in tender joint count; >=70% improvement in swollen joint count; and >=70% improvement in at least 3 of the 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and C-reactive protein (a laboratory marker of inflammation that is sensitive to acute changes in inflammatory response). All improvements were assessed relative to the baseline of the prior study.	Week 520
Number of Participants Meeting American College of Rheumatology 70% (ACR70) Response Criteria at Week 260	ACR70 response criteria were: >=70% improvement in tender joint count; >=70% improvement in swollen joint count; and >=70% improvement in at least 3 of the 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and C-reactive protein (a laboratory marker of inflammation that is sensitive to acute changes in inflammatory response). All improvements were assessed relative to the baseline of the prior study.	Week 260
Number of Participants in Clinical Remission (Based on Modified Disease Activity Score) at Week 520	Clinical remission on modified Disease Activity Score (DAS28) was a value <2.6; >=2.6 to <=3.2 indicated low disease activity; >3.2 to <=5.1 indicated moderate disease activity; and >5.1 indicated high disease activity. DAS28 score is calculated using the number of tender joints and swollen joints (out of 28 each), patient global assessment of disease activity, and C-reactive protein (a laboratory marker of inflammation that is sensitive to acute changes in inflammatory response).	Week 520
Number of Participants in Clinical Remission (Based on Modified Disease Activity Score) at Week 260	Clinical remission on modified Disease Activity Score (DAS28) was a value <2.6; >=2.6 to <=3.2 indicated low disease activity; >3.2 to <=5.1 indicated moderate disease activity; and >5.1 indicated high disease activity. DAS28 score is calculated using the number of tender joints and swollen joints (out of 28 each), patient global assessment of disease activity, and C-reactive protein (a laboratory marker of inflammation that is sensitive to acute changes in inflammatory response).	Week 260
Change From Baseline in the Disability Index of the Health Assessment Questionnaire (HAQ) at Week 520	The HAQ-DI is a measure of disability that ranges from 0 to 3. Decrease in score indicates improvement in physical function; a decrease of 0.22 or greater from Baseline score is clinically significant. Participants assessed their ability to perform at least 6 of the following 8 specific tasks (1. dress/groom; 2. arise; 3. eat; 4. walk; 5. reach; 6. grip; 7. maintain hygiene; 8. maintain daily activity) over the past week by marking their response on a questionnaire. Possible responses/scores included the following: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). The 8 task scores are added and the sum is divided by the number of tasks assessed (range = 6 to 8). This yields a HAQ-DI score of 0 to 3.	Baseline of prior Phase 1, 2, or 3 adalimumab study and Week 520
Change From Baseline in the Disability Index of the Health Assessment Questionnaire (HAQ) at Week 260	The HAQ-DI is a measure of disability that ranges from 0 to 3. Decrease in score indicates improvement in physical function; a decrease of 0.22 or greater from Baseline score is clinically significant. Participants assessed their ability to perform at least 6 of the following 8 specific tasks (1. dress/groom; 2. arise; 3. eat; 4. walk; 5. reach; 6. grip; 7. maintain hygiene; 8. maintain daily activity) over the past week by marking their response on a questionnaire. Possible responses/scores included the following: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). The 8 task scores are added and the sum is divided by the number of tasks assessed (range = 6 to 8). This yields a HAQ-DI score of 0 to 3.	Baseline of prior Phase 1, 2, or 3 adalimumab study and Week 260

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reported Adverse Events	Adverse events were collected during the course of the study (after the first adalimumab injection in this continuation study DE020 through 70 days after the last adalimumab injection) for all participants who received at least 1 dose of open-label adalimumab in the continuation study (Full Analysis Set). The number of participants experiencing any adverse event (serious and non-serious) are summarized. See the Reported Adverse Events section for details.	Duration of study (up to 520 weeks [10 years])

Collaborators and Investigators

• Sponsor: Abbott
• Investigators: Study Director: Hartmut Kupper, MD, Abbott

Publications and helpful links

General Publications

• Furst DE, Kavanaugh A, Florentinus S, Kupper H, Karunaratne M, Birbara CA. Final 10-year effectiveness and safety results from study DE020: adalimumab treatment in patients with rheumatoid arthritis and an inadequate response to standard therapy. Rheumatology (Oxford). 2015 Dec;54(12):2188-97. doi: 10.1093/rheumatology/kev249. Epub 2015 Jul 21.

Study record dates

Study Major Dates

• Study Start: July 1, 2000
• Primary Completion (Actual): May 1, 2011
• Study Completion (Actual): May 1, 2011

Study Registration Dates

• First Submitted: September 13, 2005
• First Submitted That Met QC Criteria: September 13, 2005
• First Posted (Estimate): September 20, 2005

Study Record Updates

• Last Update Posted (Estimate): August 31, 2012
• Last Update Submitted That Met QC Criteria: August 24, 2012
• Last Verified: August 1, 2012

More Information

Terms related to this study

• Keywords: Rheumatoid Arthritis
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Anti-Inflammatory Agents; Antirheumatic Agents; Adalimumab
• Other Study ID Numbers: DE020