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

Moderate to Severe Rheumatoid Arthritis Clinical Trial

— ROCkIES  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01927757
• Other study ID #: 20120125
• Status: Terminated
• Phase: Phase 4
• First received: June 5, 2013
• Last updated: January 5, 2018
• Start date: May 6, 2013
• Est. completion date: June 11, 2015

Study information

• Verified date: January 2018
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 90
• Est. completion date: June 11, 2015
• Est. primary completion date: June 11, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Moderate to Severe Rheumatoid Arthritis

Intervention

Biological:
• Etanercept
Administered by subcutaneous injection

Drug:
• Methotrexate
Background methotrexate at least 15 mg weekly

Locations

Country	Name	City	State
Canada	Research Site	Burlington	Ontario
Canada	Research Site	Hamilton	Ontario
Canada	Research Site	Mississauga	Ontario
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Quebec
Canada	Research Site	Quebec City	Quebec
Canada	Research Site	Quispamsis	New Brunswick
Canada	Research Site	St. John's	Newfoundland and Labrador
Canada	Research Site	St. John's	Newfoundland and Labrador
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Victoria	British Columbia
Puerto Rico	Research Site	Caguas
United States	Research Site	Austin	Texas
United States	Research Site	Battle Creek	Michigan
United States	Research Site	Bowling Green	Kentucky
United States	Research Site	Brandon	Florida
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Chesapeake	Virginia
United States	Research Site	Clarksburg	West Virginia
United States	Research Site	Corpus Christi	Texas
United States	Research Site	Covina	California
United States	Research Site	Denver	Colorado
United States	Research Site	Duncansville	Pennsylvania
United States	Research Site	Dunedin	Florida
United States	Research Site	Fall River	Massachusetts
United States	Research Site	Hemet	California
United States	Research Site	Hixson	Tennessee
United States	Research Site	Houston	Texas
United States	Research Site	Largo	Florida
United States	Research Site	Lawrenceville	Georgia
United States	Research Site	Lincoln	Nebraska
United States	Research Site	Middleburg Heights	Ohio
United States	Research Site	Murrieta	California
United States	Research Site	Paducah	Kentucky
United States	Research Site	Palm Harbor	Florida
United States	Research Site	Roanoke	Virginia
United States	Research Site	San Diego	California
United States	Research Site	Scottsdale	Arizona
United States	Research Site	Seattle	Washington
United States	Research Site	Smithtown	New York
United States	Research Site	Tampa	Florida
United States	Research Site	Tuscaloosa	Alabama
United States	Research Site	Victoria	Texas
United States	Research Site	Victorville	California

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

United States,  Canada,  Puerto Rico, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

•   AmgenTrials clinical trials website