Long Term Open Label Continuation Study

Rheumatoid Arthritis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00195650
• Other study ID #: DE020
• Status: Completed
• Phase: Phase 3
• First received: September 13, 2005
• Last updated: August 24, 2012
• Start date: July 2000
• Est. completion date: May 2011

Study information

• Verified date: August 2012
• Source: Abbott
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCanada: Health Canada
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 846
• Est. completion date: May 2011
• Est. primary completion date: May 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Biological:
• Adalimumab
Subcutaneous injection of 40 mg adalimumab every other week (eow) or monthly for up to 520 weeks (10 years)

Locations

Country	Name	City	State
Canada	Site Reference ID/Investigator# 513	Calgary
Canada	Site Reference ID/Investigator# 568	Charlottetown
Canada	Site Reference ID/Investigator# 564	Hamilton
Canada	Site Reference ID/Investigator# 565	Hamilton
Canada	Site Reference ID/Investigator# 569	Kitchener
Canada	Site Reference ID/Investigator# 3440	Montreal
Canada	Site Reference ID/Investigator# 413	Montreal
Canada	Site Reference ID/Investigator# 66805	North York
Canada	Site Reference ID/Investigator# 66807	North York
Canada	Site Reference ID/Investigator# 414	Ottawa
Canada	Site Reference ID/Investigator# 566	Pointe-Claire
Canada	Site Reference ID/Investigator# 2467	Sainte-Foy, Quebec
Canada	Site Reference ID/Investigator# 66804	Scarborough
Canada	Site Reference ID/Investigator# 563	St. John's
Canada	Site Reference ID/Investigator# 2466	Toronto
Canada	Site Reference ID/Investigator# 567	Toronto
Canada	Site Reference ID/Investigator# 3442	Vancouver
Canada	Site Reference ID/Investigator# 514	Winnipeg
United States	Site Reference ID/Investigator# 562	Albuquerque	New Mexico
United States	Site Reference ID/Investigator# 66822	Anaheim	California
United States	Site Reference ID/Investigator# 408	Anchorage	Alaska
United States	Site Reference ID/Investigator# 548	Bend	Oregon
United States	Site Reference ID/Investigator# 570	Bethlehem	Pennsylvania
United States	Site Reference ID/Investigator# 549	Billings	Montana
United States	Site Reference ID/Investigator# 4111	Birmingham	Alabama
United States	Site Reference ID/Investigator# 538	Birmingham	Alabama
United States	Site Reference ID/Investigator# 4110	Boise	Idaho
United States	Site Reference ID/Investigator# 449	Boise	Idaho
United States	Site Reference ID/Investigator# 653	Boston	Massachusetts
United States	Site Reference ID/Investigator# 66823	Brooklyn	New York
United States	Site Reference ID/Investigator# 544	Chevy Chase	Maryland
United States	Site Reference ID/Investigator# 578	Chicago	Illinois
United States	Site Reference ID/Investigator# 438	Cincinnati	Ohio
United States	Site Reference ID/Investigator# 650	Coeur D'Alene	Idaho
United States	Site Reference ID/Investigator# 572	Colorado Springs	Colorado
United States	Site Reference ID/Investigator# 2435	Dallas	Texas
United States	Site Reference ID/Investigator# 541	Danbury	Connecticut
United States	Site Reference ID/Investigator# 436	Dayton	Ohio
United States	Site Reference ID/Investigator# 455	Daytona Beach	Florida
United States	Site Reference ID/Investigator# 4109	Denver	Colorado
United States	Site Reference ID/Investigator# 573	Dover	New Jersey
United States	Site Reference ID/Investigator# 553	Eugene	Oregon
United States	Site Reference ID/Investigator# 649	Everett	Washington
United States	Site Reference ID/Investigator# 66862	Everett	Washington
United States	Site Reference ID/Investigator# 431	Fort Lauderdale	Florida
United States	Site Reference ID/Investigator# 574	Fort Myers	Florida
United States	Site Reference ID/Investigator# 66843	Gainesville	Florida
United States	Site Reference ID/Investigator# 656	Glendale	Wisconsin
United States	Site Reference ID/Investigator# 4112	Indianapolis	Indiana
United States	Site Reference ID/Investigator# 531	Kirkland	Washington
United States	Site Reference ID/Investigator# 557	La Jolla	California
United States	Site Reference ID/Investigator# 432	Lake Success	New York
United States	Site Reference ID/Investigator# 387	Los Angeles	California
United States	Site Reference ID/Investigator# 555	Los Angeles	California
United States	Site Reference ID/Investigator# 547	Louisville	Kentucky
United States	Site Reference ID/Investigator# 534	Metairie	Louisiana
United States	Site Reference ID/Investigator# 654	Milford	Connecticut
United States	Site Reference ID/Investigator# 539	Milwaukee	Wisconsin
United States	Site Reference ID/Investigator# 4113	Mobile	Alabama
United States	Site Reference ID/Investigator# 647	New York	New York
United States	Site Reference ID/Investigator# 657	New York	New York
United States	Site Reference ID/Investigator# 412	Olympia	Washington
United States	Site Reference ID/Investigator# 579	Orlando	Florida
United States	Site Reference ID/Investigator# 571	Palm Harbor	Florida
United States	Site Reference ID/Investigator# 546	Petoskey	Michigan
United States	Site Reference ID/Investigator# 545	Port Jefferson Station	New York
United States	Site Reference ID/Investigator# 532	Portland	Oregon
United States	Site Reference ID/Investigator# 561	Reno	Nevada
United States	Site Reference ID/Investigator# 536	Richmond	Virginia
United States	Site Reference ID/Investigator# 575	Ridley Park	Pennsylvania
United States	Site Reference ID/Investigator# 552	Santa Barbara	California
United States	Site Reference ID/Investigator# 66864	Santa Monica	California
United States	Site Reference ID/Investigator# 651	Sarasota	Florida
United States	Site Reference ID/Investigator# 658	Spokane	Washington
United States	Site Reference ID/Investigator# 577	St. Louis	Missouri
United States	Site Reference ID/Investigator# 66863	St. Petersburg	Florida
United States	Site Reference ID/Investigator# 535	Stanford	California
United States	Site Reference ID/Investigator# 646	Statesville	North Carolina
United States	Site Reference ID/Investigator# 540	Syracuse	New York
United States	Site Reference ID/Investigator# 542	Tampa	Florida
United States	Site Reference ID/Investigator# 66842	Toms River	New Jersey
United States	Site Reference ID/Investigator# 537	Tucson	Arizona
United States	Site Reference ID/Investigator# 3412	Upland	California
United States	Site Reference ID/Investigator# 576	Vancouver	Washington
United States	Site Reference ID/Investigator# 415	Vero Beach	Florida
United States	Site Reference ID/Investigator# 559	Voorhees	New Jersey
United States	Site Reference ID/Investigator# 451	Westlake Village	California
United States	Site Reference ID/Investigator# 585	Willow Grove	Pennsylvania
United States	Site Reference ID/Investigator# 655	Wilmington	Delaware
United States	Site Reference ID/Investigator# 4114	Worcester	Massachusetts
United States	Site Reference ID/Investigator# 551	Yakima	Washington
United States	Site Reference ID/Investigator# 652	Zephyrhills	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Abbott

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Secondary	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])	Yes