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Evaluating Etanercept Use in Patients With Moderate to Severe Rheumatoid Arthritis Who Have Lost Response to Adalimumab (ROCkIES)

This study has been terminated.
(Business decision due to slow enrollment)
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT01927757
First received: June 5, 2013
Last updated: July 29, 2016
Last verified: July 2016
  Purpose
To evaluate the efficacy of etanercept in adults with moderate-to-severe rheumatoid arthritis (RA) who did not respond to or lost a satisfactory response to adalimumab when used as their first biologic agent.

Condition Intervention Phase
Moderate to Severe Rheumatoid Arthritis
Biological: Etanercept
Drug: Methotrexate
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Single Arm Trial to Evaluate the Efficacy of Etanercept in Moderate to Severe Rheumatoid Arthritis Patients Who Failed to Respond or Lost a Satisfactory Response to Treatment With Adalimumab When Used as Their First Biologic Agent

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • Percentage of Participants With an American College of Rheumatology (ACR) 20 Response at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 20% improvement in tender joint count; • ≥ 20% improvement in swollen joint count; and • ≥ 20% improvement in at least 3 of the 5 following parameters: o Patient Global Assessment of Joint Pain (measured on a 100 mm VAS); o Patient Global Assessment of Disease Activity (measured on a horizontal scale from 0 to 100); o Physician Global Assessment of Disease Activity (measured on a horizontal scale from 0 to 100); o Health Assessment Questionnaire - Disability Index (HAQ-DI) scale from 0 to 3, where zero represents no disability and three very severe, high-dependency disability; o C-reactive protein level.


Secondary Outcome Measures:
  • Percentage of Participants With an ACR 20 Response at Week 12 by Anti-adalimumab Antibody Subgroup [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 20% improvement in tender joint count; • ≥ 20% improvement in swollen joint count; and • ≥ 20% improvement in at least 3 of the 5 following parameters: o Patient Global Assessment of Joint Pain (measured on a 100 mm VAS); o Patient Global Assessment of Disease Activity (measured on a horizontal scale from 0 to 100); o Physician Global Assessment of Disease Activity (measured on a horizontal scale from 0 to 100); o Health Assessment Questionnaire - Disability Index (HAQ-DI) scale from 0 to 3, where zero represents no disability and three very severe, high-dependency disability; o C-reactive protein level.

  • Percentage of Participants With an ACR 20 Response at Week 12 by Response Failure Type Subgroup [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 20% improvement in tender joint count; • ≥ 20% improvement in swollen joint count; and • ≥ 20% improvement in at least 3 of the 5 following parameters: o Patient Global Assessment of Joint Pain (measured on a 100 mm VAS); o Patient Global Assessment of Disease Activity (measured on a horizontal scale from 0 to 100); o Physician Global Assessment of Disease Activity (measured on a horizontal scale from 0 to 100); o Health Assessment Questionnaire - Disability Index (HAQ-DI) scale from 0 to 3, where zero represents no disability and three very severe, high-dependency disability; o C-reactive protein level.

  • Percentage of Participants With an ACR 20 Response at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 20% improvement in tender joint count; • ≥ 20% improvement in swollen joint count; and • ≥ 20% improvement in at least 3 of the 5 following parameters: o Patient Global Assessment of Joint Pain (measured on a 100 mm VAS); o Patient Global Assessment of Disease Activity (measured on a horizontal scale from 0 to 100); o Physician Global Assessment of Disease Activity (measured on a horizontal scale from 0 to 100); o Health Assessment Questionnaire - Disability Index (HAQ-DI) scale from 0 to 3, where zero represents no disability and three very severe, high-dependency disability; o C-reactive protein level.

  • Percentage of Participants With an ACR 50 Response at Weeks 12 and 24 [ Time Frame: Baseline and Weeks 12 and 24 ] [ Designated as safety issue: No ]
    A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 50% improvement in tender joint count; • ≥ 50% improvement in swollen joint count; and • ≥ 50% improvement in at least 3 of the 5 following parameters: o Patient Global Assessment of Joint Pain (measured on a 100 mm VAS); o Patient Global Assessment of Disease Activity (measured on a horizontal scale from 0 to 100); o Physician Global Assessment of Disease Activity (measured on a horizontal scale from 0 to 100); o Health Assessment Questionnaire - Disability Index (HAQ-DI) scale from 0 to 3, where zero represents no disability and three very severe, high-dependency disability; o C-reactive protein level.

  • Percentage of Participants With an ACR 70 Response at Weeks 12 and 24 [ Time Frame: Baseline and Weeks 12 and 24 ] [ Designated as safety issue: No ]
    A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 70% improvement in tender joint count; • ≥ 70% improvement in swollen joint count; and • ≥ 70% improvement in at least 3 of the 5 following parameters: o Patient Global Assessment of Joint Pain (measured on a 100 mm VAS); o Patient Global Assessment of Disease Activity (measured on a horizontal scale from 0 to 100); o Physician Global Assessment of Disease Activity (measured on a horizontal scale from 0 to 100); o Health Assessment Questionnaire - Disability Index (HAQ-DI) scale from 0 to 3, where zero represents no disability and three very severe, high-dependency disability; o C-reactive protein level.

  • Change From Baseline in Disease Activity Score 28-C-Reactive Protein (DAS28-CRP) [ Time Frame: Baseline and weeks 12 and 24 ] [ Designated as safety issue: No ]

    The DAS28-CRP is a composite score to measure disease activity in patients with rheumatoid arthritis, derived from the following variables:

    • The number of swollen and tender joints assessed using the 28-joint count;
    • C-reactive protein (CRP) level
    • Patient's global assessment of disease activity assessed on a score from 0 to 100.

    The DAS28-CRP score ranges from zero up to approximately ten. DAS28-CRP scores above 5.1 indicate high disease activity. A negative change from baseline indicates improvement.


  • Percentage of Participants With DAS28-CRP Improvement of ≥ 1.2 Units From Baseline [ Time Frame: Baseline and weeks 12 and 24 ] [ Designated as safety issue: No ]
    The DAS28-CRP is a composite score to measure disease activity in patients with rheumatoid arthritis, derived from the following variables: • The number of swollen and tender joints assessed using the 28-joint count; • C-reactive protein (CRP) level • Patient's global assessment of disease activity assessed on a score from 0 to 100. The DAS28-CRP score ranges from zero up to approximately ten. DAS28-CRP scores above 5.1 indicate high disease activity.

  • Percentage of Participants With DAS 28-CRP < 3.2 [ Time Frame: Weeks 12 and 24 ] [ Designated as safety issue: No ]
    The DAS28-CRP is a composite score to measure disease activity in patients with rheumatoid arthritis, derived from the following variables: • The number of swollen and tender joints assessed using the 28-joint count; • C-reactive protein (CRP) level • Patient's global assessment of disease activity assessed on a score from 0 to 100. The DAS28-CRP score ranges from zero up to approximately ten. DAS28-CRP scores less than 3.2 are considered low disease activity.

  • Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) [ Time Frame: Baseline and weeks 12 and 24 ] [ Designated as safety issue: No ]
    The HAQ-DI is a questionnaire on which participants are asked to rate their level of difficulty on daily activities (dressing and grooming, arising, eating, and walking) and personal abilities (hygiene, reach, grip, and activity) as well as their use of aids, devices, or help from another person for these activities and disabilities. Responses are scored from 0 indicating no difficulty to 3 indicating inability to perform a task in that area. The overall score is the average of each of the 8 category scores and ranges from 0 (no disability) to 3 (very severe, high-dependency disability).

  • Change From Baseline in 36-item Short Form Health Survey (SF-36) at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    The Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) is a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). Norm-based scores were used in analyses of each domain, calibrated so that 50 is the average score and the standard deviation equals 10. Higher scores indicate a higher level of functioning.

  • Change From Baseline in 36-item Short Form Health Survey (SF-36) at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    The Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) is a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). Norm-based scores were used in analyses of each domain, calibrated so that 50 is the average score and the standard deviation equals 10. Higher scores indicate a higher level of functioning.

  • Work Productivity and Activity Impairment (WPAI) [ Time Frame: Baseline, week 12 and week 24 ] [ Designated as safety issue: No ]
    This 6-item assessment measures productivity losses during the past 7 days and includes measures on work time missed due to health, impairment while working due to health (the participant's assessment of the degree to which health affected their productivity while working), overall work impairment due to health (takes into account both hours missed due to health and the participant's assessment of the degree to which health affected their productivity while working) and activity impairment due to health (the degree in which health problems affected their ability to do regular daily activities). Scores for each measure are expressed from 0 to 100 with higher numbers indicating greater impairment and less productivity, i.e., worse outcomes.


Enrollment: 90
Study Start Date: May 2013
Study Completion Date: June 2015
Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Etanercept
Participants received etanercept 50 mg administered subcutaneously once a week with methotrexate for 24 weeks
Biological: Etanercept
Administered by subcutaneous injection
Other Name: Enbrel®
Drug: Methotrexate
Background methotrexate at least 15 mg weekly

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Able to provide informed consent
  • Diagnosed with moderate to severe rheumatoid arthritis for at least 6 months
  • Active RA with at least 3 swollen and tender joints
  • Failure to respond to a combination treatment of adalimumab and methotrexate (must have taken combination at least 3 months) or loss of a satisfactory response to the combination of adalimumab and methotrexate, which was taken for at least 6 months (if currently taking adalimumab must complete 2 weeks without it prior to starting study drug)
  • Negative for hepatitis B and C
  • Negative serum and urine pregnancy tests before starting study
  • currently taking (stable dose) 15 mg methotrexate weekly for at least 8 weeks/has been taking methotrexate for at least 12 weeks total - lower dose of 10 mg per week is permitted with documented intolerability
  • Normal chest X-ray within 3 months
  • Negative testing for tuberculosis (TB)

Exclusion Criteria:

  • Class IV RA (wheel-chair or bed-bound)
  • Significant concurrent medical conditions, including: (uncontrolled type 1 diabetes, poorly controlled type 2 diabetes, symptomatic heart failure, myocardial infarction in past year, history of unstable angina within past year, uncontrolled hypertension, severe chronic pulmonary disease, major chronic inflammatory or connective tissue disease other than RA, Multiple sclerosis, active malignancy, or history of cancer, alcoholic hepatitis or history of alcoholic liver disease)
  • Other inclusion/exclusion criteria may apply
  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: NCT01927757

  Show 45 Study Locations
Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT01927757     History of Changes
Other Study ID Numbers: 20120125 
Study First Received: June 5, 2013
Results First Received: May 30, 2016
Last Updated: July 29, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Amgen:
rheumatoid arthritis
etanercept
arthritis
adalimumab failure to respond
loss of response to adalimumab
ACR20
methotrexate
Swollen joints
tender joints

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Methotrexate
Etanercept
Adalimumab
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents

ClinicalTrials.gov processed this record on September 30, 2016