Open-Label Extension Treatment With Etanercept (TNFR:Fc) for Participating Patients in Etanercept (TNFR:Fc) Clinical Trial 016.0012

This is an open label, multicenter study for extended treatment of patients who have participated in the Immunex clinical study 016.0012. The primary objective of this study is to evaluate the long term safety of etanercept (TNFR:Fc) in patients with early stage rheumatoid arthritis.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 468
• Phase: Phase 3

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: - Previous enrollment in Immunex protocol 016.0012.

• No clinically significant adverse events thought to be due to etanercept (TNFR:Fc) during previous treatment.
• Negative serum pregnancy test not more than 14 days before the first dose of study drug in females of childbearing potential.
• No more than one NSAID at a dose not greater than the maximum recommended dose and stable for at least two weeks prior to administration of etanercept (TNFR:Fc). Exclusion Criteria:
• Previous receipt of etanercept (TNFR:Fc) (p55), antibody to TNF, anti-CD4 antibody, or diphtheria IL-2 fusion protein.
• Receipt of investigational drugs or biologics (other than etanercept (TNFR:Fc)) within interval between study drug in 016.0012 and this study.
• Receipt of DMARDs (e.g., hydroxychloroquine, oral or injectable gold, azathioprine, cyclosporin, D-penicillamine, sulfasalazine, minocycline, or leflunomide) other than MTX within two weeks prior to the first dose of etanercept (TNFR:Fc) in this study.
• Receipt of cyclophosphamide within 1 month prior to the first dose of etanercept (TNFR:Fc) in this study.

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
Other: 1	Biological: Etanercept; Etanercept (TNFR:Fc) will be administered 50 mg per week as two 25 mg subcutaneous injections at separate sites, given either on the same day or 3 or 4 days apart.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Exposure to Etanercept With Gaps	Total participant exposure to etanercept (Enbrel) with gaps, calculated as the sum of the times on treatment for all participants. Gaps of up to 14 days from the last treatment in a previous Etanercept study were ignored in calculating time on treatment.	Up to 8 years
Total Exposure-Adjusted Rate of Malignancies	Exposure-adjusted rate of malignancies, excluding nonmelanoma skin cancers, occurring on study within 30 days of the last dose of etanercept	Up to 8 years
Total Exposure-Adjusted Rate of Deaths	Rate of deaths within 30 days of the last dose of etanercept, adjusted for total exposure to etanercept	Up to 8 years
Total Exposure Adjusted Rate of Serious Infectious Events	Exposure-adjusted rate of serious infectious events (associated with hospitalization or IV antibiotics) occurring on study within 30 days of the last dose of etanercept	Up to 8 years
Total Exposure Adjusted Rate of Lymphomas	Rate of lymphomas occurring on study within 30 days of the last dose of etanercept, adjusted for total exposure to etanercept	Up to 8 years
Malignancy	Occurrence of one or more malignancies within the participant on study within 30 days of the last dose of etanercept	Up to 8 years
Lymphoma	Occurrence of one or more lymphomas on study within 30 days of the last dose of etanercept	Up to 8 years
Serious Infectious Event	Occurrence of one or more serious infectious events within the participant on study within 30 days of the last dose of study medication	Up to 8 years
Total Exposure Adjusted Rate of Serious Adverse Events	Rate of serious adverse events adjusted to total exposure to etanercept (events / exposure * 100)	Up to 8 years
Death	Death of the participant on study up to 30 days after the last dose of etanercept	Up to 8 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ACR20 Response at Month 3	American College of Rheumatology (ACR) 20, defined as a 20% improvement in both tender and swollen joints (78 joints) and a 20% improvement in 3 of 5 items (physician and patient global assessments, patient pain assessment, patient self-assessed disability, and acute-phase C-reactive protein or erythrocyte sedimentation rate)	Baseline and month 3
Dosing Period	Duration of etanercept dosing	Up to 8 years
ACR20 Response at Month 12	American College of Rheumatology (ACR) 20, defined as a 20% improvement in both tender and swollen joints (78 joints) and a 20% improvement in 3 of 5 items (including physician and patient global assessments), in adults	Baseline and month 12
ACR50 Response at Month 12	American College of Rheumatology (ACR) 50, defined as a 50% improvement in both tender and swollen joints (78 joints) and a 50% improvement in 3 of 5 items (including physician and patient global assessments), in adults	Baseline and month 12
ACR70 Response at Month 12	American College of Rheumatology (ACR) 70, defined as a 70% improvement in both tender and swollen joints (78 joints) and a 70% improvement in 3 of 5 items (including physician and patient global assessments), in adults	Baseline and month 12
Standardized Incidence Rate for All SEER Cancers	Standardized incidence rate for all cancers tracked by the National Cancer Institute's Surveillance Epidemiology and End Results (SEER) system, calculated as the ratio of the observed to expected age- and sex-adjusted incidence rates (per person-year) of cancer. Expected rates were based on 1998-2002 SEER data.	Up to 8 years
Percent Improvement in Physician Global Assessment of Disease Status From Baseline to Month 12	Percent improvement in the Physician Global Assessment of disease status from baseline to month 12, assessed using a 0 - 10 Likert scale, where 0 = asymptomatic and 10 = severe symptoms	Baseline and month 12
Percent Improvement in Participant Global Assessment of Disease Status From Baseline to Month 12	Percent improvement in the Participant Global Assessment of disease status from baseline to month 12, assessed using a 0 - 10 Likert scale, where 0 = asymptomatic and 10 = severe symptoms	Baseline and Month 12
Percent Improvement in Participant Pain Visual Analog Scale From Baseline to Month 12	Percent improvement in the Participant Pain Visual Analog Scale (VAS) from baseline to month 12, using a 10 cm scale ranging from "no pain" (0 cm) to "severe pain" (10 cm).	Baseline and month 12
Percent Improvement in Tender Joint Count From Baseline to Month 12	Percent improvement in tender joint count (based on up to 71 joints) from baseline to month 12. Tender joints were assessed clinically, and the number of such joints was counted at each time point.	Baseline and month 12
Percent Improvement in Swollen Joint Count From Baseline to Month 12	Percent improvement in swollen joint count (based on up to 68 joints) from baseline to month 12.	Baseline and month 12
Percent Improvement in HAQ DI From Baseline to Month 12	Percent improvement in the Health Assessment Questionnaire Disability Index (HAQ DI) from baseline to month 12.	Baseline and month 12
Percent Improvement in the Physical Component Summary Score for SF-36 From Baseline to Month 12	Percent improvement in the Physical Component Summary Score for the Short Form 36 Health Survey (SF-36) from baseline to month 12. This score has a range of 0 to 100, with higher scores indicating better health.	Baseline and month 12
Percent Improvement in Mental Component Summary Score of SF-36 From Baseline to Month 12	Percent improvement in the Mental Component Summary Score of the Short Form 36 Health Survey (SF-36) from baseline to month 12. This score has a range of 0 to 100, with higher scores indicating better health.	Baseline and month 12
Percent Improvement in C-Reactive Protein From Baseline to Month 12	Percent improvement in C-reactive protein from baseline to month 12	Baseline and month 12
Percent Improvement in Duration of Morning Stiffness From Baseline to Month 12	Percent improvement in the duration of morning stiffness from baseline to month 12	Baseline and month 12
Change From Baseline to Year 2 in Total Sharp Score	Change from baseline to year 2 in Total Sharp Score. This score has a range of 0 to 398, where 0 = no change and higher scores represent a worsening of joint erosions and joint space narrowing.	Baseline, Year 2
Change From Baseline to Year 2 in Sharp Score Erosion Subscale	Change from baseline to year 2 in the joint erosion subscale of the Total Sharp Score. This subscale has a range of 0 to 230, where 0 = no change and higher values represent a worsening in joint erosions.	Baseline, Year 2
Change From Baseline to Year 2 in Sharp Score Joint Space Narrowing Subscale	Change from baseline to year 2 in the joint space narrowing subscale of the Total Sharp Score. This subscale has a range of 0 to 168, where 0 = no change and higher values represent a worsening of joint space narrowing.	Baseline, Year 2

Collaborators and Investigators

• Sponsor: Amgen
• Collaborators: Immunex Corporation

Publications and helpful links

General Publications

• Weinblatt ME, Bathon JM, Kremer JM, Fleischmann RM, Schiff MH, Martin RW, Baumgartner SW, Park GS, Mancini EL, Genovese MC. Safety and efficacy of etanercept beyond 10 years of therapy in North American patients with early and longstanding rheumatoid arthritis. Arthritis Care Res (Hoboken). 2011 Mar;63(3):373-82. doi: 10.1002/acr.20372. Epub 2010 Oct 18.
• Genovese MC, Bathon JM, Fleischmann RM, Moreland LW, Martin RW, Whitmore JB, Tsuji WH, Leff JA. Longterm safety, efficacy, and radiographic outcome with etanercept treatment in patients with early rheumatoid arthritis. J Rheumatol. 2005 Jul;32(7):1232-42.
• Genovese MC, Bathon JM, Martin RW, Fleischmann RM, Tesser JR, Schiff MH, Keystone EC, Wasko MC, Moreland LW, Weaver AL, Markenson J, Cannon GW, Spencer-Green G, Finck BK. Etanercept versus methotrexate in patients with early rheumatoid arthritis: two-year radiographic and clinical outcomes. Arthritis Rheum. 2002 Jun;46(6):1443-50. doi: 10.1002/art.10308.

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start: December 1, 1998
• Primary Completion (Actual): December 1, 2008
• Study Completion (Actual): April 1, 2009

Study Registration Dates

• First Submitted: July 24, 2006
• First Submitted That Met QC Criteria: July 24, 2006
• First Posted (Estimate): July 26, 2006

Study Record Updates

• Last Update Posted (Estimate): May 14, 2013
• Last Update Submitted That Met QC Criteria: May 10, 2013
• Last Verified: May 1, 2013

More Information

Terms related to this study

• Keywords: Rheumatoid Arthritis; Enbrel; Etanercept; Long-term Safety
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Gastrointestinal Agents; Etanercept
• Other Study ID Numbers: 20021623; 16.0023