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

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

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.

Study Overview

• Status: Terminated
• Conditions: Moderate to Severe Rheumatoid Arthritis
• Intervention / Treatment: Biological: Etanercept; Drug: Methotrexate

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1V 3M7
    • Research Site
  • British Columbia
    • Victoria, British Columbia, Canada, V8V 3P9
      • Research Site
  • New Brunswick
    • Quispamsis, New Brunswick, Canada, E2E 4J8
      • Research Site
  • Newfoundland and Labrador
    • St. John's, Newfoundland and Labrador, Canada, A1C 5B8
      • Research Site
    • St. John's, Newfoundland and Labrador, Canada, A1A 5E8
      • Research Site
  • Ontario
    • Burlington, Ontario, Canada, L7R 1E2
      • Research Site
    • Hamilton, Ontario, Canada, L8N 1Y2
      • Research Site
    • Mississauga, Ontario, Canada, L5M 2V8
      • Research Site
    • Toronto, Ontario, Canada, M5G 1X5
      • Research Site
  • Quebec
    • Montreal, Quebec, Canada, H2L 1S6
      • Research Site
    • Montreal, Quebec, Canada, H3T 1Y3
      • Research Site
    • Quebec City, Quebec, Canada, G1W 4R4
      • Research Site
• Puerto Rico
  • Caguas, Puerto Rico, 00725
    • Research Site
• United States
  • Alabama
    • Tuscaloosa, Alabama, United States, 35406
      • Research Site
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Research Site
  • California
    • Covina, California, United States, 91723
      • Research Site
    • Hemet, California, United States, 92543
      • Research Site
    • Murrieta, California, United States, 92563
      • Research Site
    • San Diego, California, United States, 92108
      • Research Site
    • Victorville, California, United States, 92395
      • Research Site
  • Colorado
    • Denver, Colorado, United States, 80230
      • Research Site
  • Florida
    • Brandon, Florida, United States, 33511
      • Research Site
    • Dunedin, Florida, United States, 34698
      • Research Site
    • Largo, Florida, United States, 33774
      • Research Site
    • Palm Harbor, Florida, United States, 34684
      • Research Site
    • Tampa, Florida, United States, 33609
      • Research Site
  • Georgia
    • Lawrenceville, Georgia, United States, 30046
      • Research Site
  • Kentucky
    • Bowling Green, Kentucky, United States, 42101
      • Research Site
    • Paducah, Kentucky, United States, 42003
      • Research Site
  • Massachusetts
    • Fall River, Massachusetts, United States, 02720
      • Research Site
  • Michigan
    • Battle Creek, Michigan, United States, 49017
      • Research Site
  • Nebraska
    • Lincoln, Nebraska, United States, 68516
      • Research Site
  • New York
    • Smithtown, New York, United States, 11787
      • Research Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28210
      • Research Site
  • Ohio
    • Middleburg Heights, Ohio, United States, 44130
      • Research Site
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Research Site
  • Tennessee
    • Hixson, Tennessee, United States, 37343
      • Research Site
  • Texas
    • Austin, Texas, United States, 78731
      • Research Site
    • Corpus Christi, Texas, United States, 78404
      • Research Site
    • Houston, Texas, United States, 77034
      • Research Site
    • Victoria, Texas, United States, 77901
      • Research Site
  • Virginia
    • Chesapeake, Virginia, United States, 23320
      • Research Site
    • Roanoke, Virginia, United States, 24016
      • Research Site
  • Washington
    • Seattle, Washington, United States, 98133
      • Research Site
  • West Virginia
    • Clarksburg, West Virginia, United States, 26301
      • Research Site

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:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Etanercept; Participants received etanercept 50 mg administered subcutaneously once a week with methotrexate for 24 weeks	Biological: Etanercept; Administered by subcutaneous injection; Other Names: Enbrel®; Drug: Methotrexate; Background methotrexate at least 15 mg weekly

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With an American College of Rheumatology (ACR) 20 Response at Week 12	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.	Baseline and Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With an ACR 20 Response at Week 12 by Anti-adalimumab Antibody Subgroup	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.	Baseline and Week 12
Percentage of Participants With an ACR 20 Response at Week 12 by Response Failure Type Subgroup	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.	Baseline and Week 12
Percentage of Participants With an ACR 20 Response at Week 24	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.	Baseline and Week 24
Percentage of Participants With an ACR 50 Response at Weeks 12 and 24	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.	Baseline and Weeks 12 and 24
Percentage of Participants With an ACR 70 Response at Weeks 12 and 24	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.	Baseline and Weeks 12 and 24
Change From Baseline in Disease Activity Score 28-C-Reactive Protein (DAS28-CRP)	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.	Baseline and weeks 12 and 24
Percentage of Participants With DAS28-CRP Improvement of ≥ 1.2 Units From Baseline	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.	Baseline and weeks 12 and 24
Percentage of Participants With DAS 28-CRP < 3.2	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.	Weeks 12 and 24
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI)	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).	Baseline and weeks 12 and 24
Change From Baseline in 36-item Short Form Health Survey (SF-36) at Week 12	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.	Baseline and Week 12
Change From Baseline in 36-item Short Form Health Survey (SF-36) at Week 24	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.	Baseline and Week 24
Work Productivity and Activity Impairment (WPAI)	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.	Baseline, week 12 and week 24

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

General Publications

• Bessette L, Khraishi M, Kivitz AJ, Kaliyaperumal A, Grantab R, Poulin-Costello M, Isaila M, Collier D. Single-Arm Study of Etanercept in Adult Patients with Moderate to Severe Rheumatoid Arthritis Who Failed Adalimumab Treatment. Rheumatol Ther. 2017 Dec;4(2):391-404. doi: 10.1007/s40744-017-0079-x. Epub 2017 Sep 12.

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): May 6, 2013
• Primary Completion (Actual): June 11, 2015
• Study Completion (Actual): June 11, 2015

Study Registration Dates

• First Submitted: June 5, 2013
• First Submitted That Met QC Criteria: August 20, 2013
• First Posted (Estimate): August 23, 2013

Study Record Updates

• Last Update Posted (Actual): January 30, 2018
• Last Update Submitted That Met QC Criteria: January 5, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: rheumatoid arthritis; methotrexate; arthritis; ACR20; etanercept; Swollen joints; adalimumab failure to respond; loss of response to adalimumab; tender joints
• 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; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gastrointestinal Agents; Dermatologic Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Etanercept; Methotrexate
• Other Study ID Numbers: 20120125