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

This study has been completed.
Sponsor:
Collaborator:
Immunex Corporation
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT00356590
First received: July 24, 2006
Last updated: May 10, 2013
Last verified: May 2013
  Purpose

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.


Condition Intervention Phase
Rheumatoid Arthritis
Biological: Etanercept
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Open-Label Extension Treatment With Etanercept (TNFR:Fc) for Participating Patients in Etanercept (TNFR:Fc) Clinical Trial 016.0012

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • Total Exposure to Etanercept With Gaps [ Time Frame: Up to 8 years ] [ Designated as safety issue: No ]
    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.

  • Total Exposure-Adjusted Rate of Malignancies [ Time Frame: Up to 8 years ] [ Designated as safety issue: Yes ]
    Exposure-adjusted rate of malignancies, excluding nonmelanoma skin cancers, occurring on study within 30 days of the last dose of etanercept

  • Total Exposure-Adjusted Rate of Deaths [ Time Frame: Up to 8 years ] [ Designated as safety issue: Yes ]
    Rate of deaths within 30 days of the last dose of etanercept, adjusted for total exposure to etanercept

  • Total Exposure Adjusted Rate of Serious Infectious Events [ Time Frame: Up to 8 years ] [ Designated as safety issue: Yes ]
    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

  • Total Exposure Adjusted Rate of Lymphomas [ Time Frame: Up to 8 years ] [ Designated as safety issue: Yes ]
    Rate of lymphomas occurring on study within 30 days of the last dose of etanercept, adjusted for total exposure to etanercept

  • Malignancy [ Time Frame: Up to 8 years ] [ Designated as safety issue: Yes ]
    Occurrence of one or more malignancies within the participant on study within 30 days of the last dose of etanercept

  • Lymphoma [ Time Frame: Up to 8 years ] [ Designated as safety issue: Yes ]
    Occurrence of one or more lymphomas on study within 30 days of the last dose of etanercept

  • Serious Infectious Event [ Time Frame: Up to 8 years ] [ Designated as safety issue: Yes ]
    Occurrence of one or more serious infectious events within the participant on study within 30 days of the last dose of study medication

  • Total Exposure Adjusted Rate of Serious Adverse Events [ Time Frame: Up to 8 years ] [ Designated as safety issue: Yes ]
    Rate of serious adverse events adjusted to total exposure to etanercept (events / exposure * 100)

  • Death [ Time Frame: Up to 8 years ] [ Designated as safety issue: No ]
    Death of the participant on study up to 30 days after the last dose of etanercept


Secondary Outcome Measures:
  • ACR20 Response at Month 3 [ Time Frame: Baseline and month 3 ] [ Designated as safety issue: No ]
    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)

  • Dosing Period [ Time Frame: Up to 8 years ] [ Designated as safety issue: No ]
    Duration of etanercept dosing

  • ACR20 Response at Month 12 [ Time Frame: Baseline and month 12 ] [ Designated as safety issue: No ]
    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

  • ACR50 Response at Month 12 [ Time Frame: Baseline and month 12 ] [ Designated as safety issue: No ]
    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

  • ACR70 Response at Month 12 [ Time Frame: Baseline and month 12 ] [ Designated as safety issue: No ]
    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

  • Standardized Incidence Rate for All SEER Cancers [ Time Frame: Up to 8 years ] [ Designated as safety issue: No ]
    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.

  • Percent Improvement in Physician Global Assessment of Disease Status From Baseline to Month 12 [ Time Frame: Baseline and month 12 ] [ Designated as safety issue: No ]
    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

  • Percent Improvement in Participant Global Assessment of Disease Status From Baseline to Month 12 [ Time Frame: Baseline and Month 12 ] [ Designated as safety issue: No ]
    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

  • Percent Improvement in Participant Pain Visual Analog Scale From Baseline to Month 12 [ Time Frame: Baseline and month 12 ] [ Designated as safety issue: No ]
    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).

  • Percent Improvement in Tender Joint Count From Baseline to Month 12 [ Time Frame: Baseline and month 12 ] [ Designated as safety issue: No ]
    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.

  • Percent Improvement in Swollen Joint Count From Baseline to Month 12 [ Time Frame: Baseline and month 12 ] [ Designated as safety issue: No ]
    Percent improvement in swollen joint count (based on up to 68 joints) from baseline to month 12.

  • Percent Improvement in HAQ DI From Baseline to Month 12 [ Time Frame: Baseline and month 12 ] [ Designated as safety issue: No ]
    Percent improvement in the Health Assessment Questionnaire Disability Index (HAQ DI) from baseline to month 12.

  • Percent Improvement in the Physical Component Summary Score for SF-36 From Baseline to Month 12 [ Time Frame: Baseline and month 12 ] [ Designated as safety issue: No ]
    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.

  • Percent Improvement in Mental Component Summary Score of SF-36 From Baseline to Month 12 [ Time Frame: Baseline and month 12 ] [ Designated as safety issue: No ]
    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.

  • Percent Improvement in C-Reactive Protein From Baseline to Month 12 [ Time Frame: Baseline and month 12 ] [ Designated as safety issue: No ]
    Percent improvement in C-reactive protein from baseline to month 12

  • Percent Improvement in Duration of Morning Stiffness From Baseline to Month 12 [ Time Frame: Baseline and month 12 ] [ Designated as safety issue: No ]
    Percent improvement in the duration of morning stiffness from baseline to month 12

  • Change From Baseline to Year 2 in Total Sharp Score [ Time Frame: Baseline, Year 2 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline to Year 2 in Sharp Score Erosion Subscale [ Time Frame: Baseline, Year 2 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline to Year 2 in Sharp Score Joint Space Narrowing Subscale [ Time Frame: Baseline, Year 2 ] [ Designated as safety issue: No ]
    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.


Enrollment: 468
Study Start Date: December 1998
Study Completion Date: April 2009
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1
N/A
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00356590

Sponsors and Collaborators
Amgen
Immunex Corporation
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT00356590     History of Changes
Other Study ID Numbers: 20021623, 16.0023
Study First Received: July 24, 2006
Results First Received: November 5, 2010
Last Updated: May 10, 2013
Health Authority: Canada: Health Canada
United States: Food and Drug Administration
United States: Western Institutional Review Board

Keywords provided by Amgen:
Rheumatoid Arthritis
Etanercept
Long-term Safety
Enbrel

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Autoimmune Diseases
Connective Tissue Diseases
Immune System Diseases
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
TNFR-Fc fusion protein
Analgesics
Analgesics, Non-Narcotic
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Antirheumatic Agents
Central Nervous System Agents
Gastrointestinal Agents
Immunologic Factors
Immunosuppressive Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014