CAMEO: Canadian Methotrexate and Etanercept Outcome Study

This study has been completed.
Sponsor:
Collaborator:
Wyeth is now a wholly owned subsidiary of Pfizer
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT00654368
First received: April 3, 2008
Last updated: July 14, 2014
Last verified: July 2014
  Purpose

The purpose of the study is to evaluate the use of etanercept in the treatment of rheumatoid arthritis with or without methotrexate treatment over a 24 month period


Condition Intervention Phase
Rheumatoid Arthritis
Biological: Etanercept
Drug: Methotrexate
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Canadian Methotrexate and Etanercept Outcome Study: An Open Label Randomized Trial of Etanercept and Methotrexate Versus Etanercept Alone in the Treatment of Rheumatoid Arthritis (CAMEO)

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • Change From Month 6 to Month 12 in Disease Activity Sscore 28 (DAS28) [ Time Frame: Month 6 (randomization) and Month 12 ] [ Designated as safety issue: No ]
    The DAS28 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; • Erythrocyte sedimentation rate (ESR); • Patient's global assessment of disease activity measured on a 100 mm visual analog scale. The DAS28 score ranges from zero to ten. A DAS28 score above 5.1 means high disease activity whereas a DAS28 less than or equal to 3.2 indicates low disease activity. In this study, the mean change in DAS28 scores from Month 6 to Month 12 was multiplied by a factor of -1, such that a negative change in DAS28 indicates worsening in disease activity.


Secondary Outcome Measures:
  • Disease Activity Score (DAS) 28 Response [ Time Frame: Month 6, 12, 18 and 24 ] [ Designated as safety issue: No ]
    The DAS28 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; • Erythrocyte sedimentation rate (ESR); • Patient's global assessment of disease activity measured on a 100 mm visual analog scale. The DAS28 score ranges from zero to ten. Remission is defined by a DAS28 score less than 2.6. Low disease activity is defined by a DAS28 score less than or equal to 3.2. Moderate is defined as a DAS28 higher than 3.2 but lower than or equal to 5.1. DAS28 above 5.1 indicates high disease activity. End of study is Month 24 or early termination.

  • Change From Baseline in Disease Activity Score 28 (DAS28) [ Time Frame: Baseline and Month 6, 12, 18 and 24 ] [ Designated as safety issue: No ]
    The DAS28 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; • Erythrocyte sedimentation rate (ESR); • Patient's global assessment of disease activity measured on a 100 mm visual analog scale. The DAS28 score ranges from zero to ten. A DAS28 score above 5.1 means high disease activity whereas a DAS28 less than or equal to 3.2 indicates low disease activity. In this study, the mean changes in DAS28 scores from Baseline were multiplied by a factor of -1, such that a negative change in DAS28 indicates worsening in disease activity. End of study is Month 24 or early termination.

  • Drug Persistence [ Time Frame: Month 6, 12, 18 and 24 ] [ Designated as safety issue: No ]
    Drug persistence is defined as the percentage of participants receiving etanercept at 6, 12, 18, and 24 months.

  • Change From Baseline in Modified Total Sharp Score (mTSS) [ Time Frame: Baseline, Month 12 and Month 24 ] [ Designated as safety issue: No ]
    The modified Total Sharp Score (mTSS) is a measure of change in joint health. X-rays of hands and feet were scored in a blinded manner by an independent reader. Joints were scored for erosions on a scale from 0 (no damage) to 5 (complete collapse) and joint space narrowing on a scale from 0 (no damage) to 4 (bony ankylosis or complete luxation). Erosion scores and narrowing scores were added to obtain the total mTSS score, ranging from 0 (normal) to 448 (maximal disease). An increase in mTSS from Baseline (represented by a positive change from Baseline score) indicates disease progression and/or joint worsening, no change represents halting of disease progression, and a decrease (negative change from Baseline score) represents improvement. End of study is Month 24 or early termination.

  • Change From Baseline in Joint Erosion Score [ Time Frame: Baseline, Month 12 and Month 24 ] [ Designated as safety issue: No ]
    X-rays of hands and feet were read centrally and in a blinded manner. Sixteen joints on each hand/wrist and 6 joints on each foot were scored for erosions on a scale of 0 to 5 (or for the feet from 0 to 10, with each side of the joint independently scored from 0 to 5) according to the following: One point is scored if erosions are discrete, rising to 2, 3, 4, or 5 depending on the amount of surface area affected (complete collapse of the bone is scored as 5). Scores were summed to calculate the total erosion score, which ranges from 0 (no erosion) to 280 (worst). A large increase in erosion score is indicative of worsening, whereas a small change or no change is indicative of inhibition of joint erosion. End of study is Month 24 or early termination.

  • Change From Baseline in Joint Space Narrowing [ Time Frame: Baseline, Month 12 and Month 24 ] [ Designated as safety issue: No ]

    X-rays of hands and feet were read centrally and in a blinded manner. Joint space narrowing (JSN) scores were recorded for each hand/wrist (15 joints) and each foot (6 joints) on a 5-point scale scored as follows:

    0 = normal; 1 = focal or doubtful; 2 = generalised, less than 50% of the original joint space; 3 = generalised, more than 50% of the original joint space or subluxation; 4 = bony ankylosis or complete luxation. The scores were summed to calculate the total JSN score ranging from 0 to 168 (worst). A large increase in joint narrowing score is indicative of worsening, whereas a small change or no change is indicative of inhibition of JSN.

    End of study is Month 24 or early termination.


  • Change From Month 6 in Health Assessment Questionnaire Disability Index (HAQ DI) [ Time Frame: Month 6, 12, 18 and 24 ] [ Designated as safety issue: No ]
    The HAQ disability index is a patient-reported questionnaire specific for rheumatoid arthritis that addresses health-related quality of life. It consists of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants choose from four response categories, ranging from 'without any difficulty' (score=0) to 'unable to do' (score=3). The overall score is the average of each of the 8 category scores and ranges from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. A negative change score indicates an improvement. End of study is Month 24 or early termination.

  • Change From Month 6 in Health Assessment Questionnaire Pain Visual Analog Scale (VAS) [ Time Frame: Month 6, 12, 18 and 24 ] [ Designated as safety issue: No ]
    The HAQ pain visual analog scale (VAS) is a measure of pain on a continuous 100 point scale. Participants were asked to indicate how much pain they had in the past week as a result of their illness on a horizontal line from 0 (no pain) to 100 (severe pain). End of study is Month 24 or early termination.

  • Change From Month 6 in Short Form 36 Health Survey (SF-36) [ Time Frame: Month 6, 12, 18 and 24 ] [ Designated as safety issue: No ]

    The SF-36 assesses the general quality of life (QOL) of participants by evaluating the domains of physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. The questionnaire consists of 36 questions that are completed by the participant.

    The SF-36 is split into two major components: physical health and mental health. Under physical health are the following four domains: physical health, bodily pain, physical functioning and physical role limitations. Under the mental health domain there are four domains; mental health, vitality, social functioning, and emotional role limitation. The individual domain scores are aggregated to derive a physical-component summary score and a mental-component summary score which range from 0 to 100, with higher scores indicating a better level of functioning.

    End of study is month 24 or early termination.


  • Change From Month 6 in Work Productivity and Activity Impairment (WPAI) [ Time Frame: Month 6, 12, 18 and 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. For each measure change from Month 6 is reported; a negative change score indicates improvement. End of study is month 24 or early termination.

  • Change From Month 6 in Treatment Satisfaction Questionnaire for Medication (TSQM) [ Time Frame: Month 6, 12, 18 and 24 ] [ Designated as safety issue: No ]
    The Treatment Satisfaction Questionnaire for Medication is a 14-item self-administered questionnaire which measures patients' experiences with their medication on four dimensions: effectiveness, side effects, convenience and global satisfaction. Optional responses are: Extremely Dissatisfied (1), Very Dissatisfied (2), Dissatisfied (3), Somewhat Satisfied (4), Satisfied (5), Very Satisfied (6), and Extremely Satisfied (7). For each dimension, responses are added and transformed to a scale from 0 - 100, where higher scores indicate greater satisfaction. Change from Month 6 is reported for each dimension; a positive change score indicates improvement. End of study is Month 24 or early termination.

  • Number of Participants With Adverse Events (AEs) [ Time Frame: 25 months ] [ Designated as safety issue: No ]
    A serious adverse event (SAE) is defined by regulatory authorities as one that: • is fatal • is life threatening • requires in-patient hospitalization or prolongation of existing hospitalization • results in persistent or significant disability/incapacity • is a congenital anomaly/birth defect • other significant medical hazard.


Enrollment: 258
Study Start Date: June 2008
Study Completion Date: February 2013
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Etanercept + Methotrexate
After six months of treatment with 50 mg/week subcutaneous etanercept added to existing methotrexate therapy of at least 15 mg/week (or 10 mg/week in case of documented intolerance to higher doses) participants were randomized to continue both etanercept plus methotrexate for an additional 18 months.
Biological: Etanercept
Commercially available etanercept administered subcutaneously at 50 mg/week.
Other Name: Enbrel®
Drug: Methotrexate
Commercially available methotrexate administed orally, subcutaneously or intramuscularly 15 mg/week (or 10 mg/week in case of documented intolerance to higher doses)
Experimental: Etanercept Only
After six months of treatment with 50 mg/week subcutaneous etanercept added to existing methotrexate therapy of at least 15 mg/week (or 10 mg/week in case of documented intolerance to higher doses) participants were randomized to discontinue methotrexate (tapered over 6 weeks) and continue etanercept alone for an additional 18 months.
Biological: Etanercept
Commercially available etanercept administered subcutaneously at 50 mg/week.
Other Name: Enbrel®
Drug: Methotrexate
Commercially available methotrexate administed orally, subcutaneously or intramuscularly 15 mg/week (or 10 mg/week in case of documented intolerance to higher doses)

Detailed Description:

This noninferiority study was a multicenter, open-label, randomized trial of patients with rheumatoid arthritis (RA). Patients who did not have an adequate response to methotrexate (MTX) had etanercept (50 mg/week subcutaneously [SC]) added to existing MTX therapy of at least 15 mg/week (or 10 mg/week in case of documented intolerance to higher doses of MTX) at baseline and were followed for 6 months. After 6 months of therapy, participants were randomized in a 1:1 ratio to one of the 2 treatment arms: either discontinue MTX (tapered over 6 weeks) and continue etanercept alone or continue both etanercept plus MTX for an additional 18 months.

  Eligibility

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

Inclusion Criteria:

  • 18 years of age or older at the baseline visit
  • An American College of Rheumatology(ACR) diagnosis of rheumatoid arthritis with onset of symptoms of at least 6 months
  • Active disease of at least 3 swollen joints from the Disease Activity Severity 28 at the baseline visit
  • A Disease Activity Severity 28 score of ≥ 3.2 at the baseline visit
  • Have not previously received etanercept therapy
  • Able to start etanercept therapy per the approved product monograph
  • Able to continue methotrexate therapy per the approved product monograph and have received a dose of at least 15 mg/wk (or 10 mg/wk in the case of documented intolerance to higher doses) for at least 12 weeks and this dose has been stable at least 4 weeks before the baseline visit
  • The patient or legally acceptable representative must provide written informed consent for participation in the study before any study specific procedures are performed

Exclusion Criteria:

  • Patients who have a positive purified protein derivative (PPD) skin test and who do not have a documented course of anti-tuberculosis therapy. Patients with a positive PPD skin test (equal to or greater than 5 mm), a negative chest x-ray at screening which should be repeated if indicated during of the study, at low risk based on exposure and travel and have initiated a course of anti-tuberculosis therapy of which at least 8 weeks have been completed would be eligible for the study. The full course of anti-tuberculosis therapy must be completed
  • Patients who have previously received infliximab or adalimumab
  • Active infections within 2 weeks of the baseline visit or during the study period
  • Any history of human immunodeficiency (HIV) infection, untreated tuberculosis, multiple sclerosis, congestive heart failure, hepatitis B, hepatitis C, cytopenia, prior or current use of cyclophosphamide or malignancy (other than basal cell carcinoma or squamous cell carcinoma of the skin, or in situ carcinoma of the cervix) in the past 5 years
  • Women who are pregnant or lactating or of childbearing potential who are not using adequate contraception
  • Receipt of any investigational therapy within 4 weeks of the initiation of study medication or during the study period
  • Presence of any significant and uncontrolled medical condition, which in the investigator's opinion precludes the use of etanercept, as outlined in the product monograph
  • Participants not available for follow-up assessment or unable to comply with study procedures
  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: NCT00654368

Locations
Canada, British Columbia
Research Site
Vancouver, British Columbia, Canada, V5Z 3Y1
Research Site
Victoria, British Columbia, Canada, V8V 3P9
Research Site
Victoria, British Columbia, Canada, V8P 5P6
Canada, Manitoba
Research Site
Winnipeg, Manitoba, Canada, R3A 1M3
Canada, New Brunswick
Research Site
Quispamsis, New Brunswick, Canada, E2E 4J8
Canada, Newfoundland and Labrador
Research Site
St. John's, Newfoundland and Labrador, Canada, A1C 5B8
Research Site
St. John's, Newfoundland and Labrador, Canada, A1A 5E8
Canada, Nova Scotia
Research Site
Sydney, Nova Scotia, Canada, B1S 3N1
Canada, Ontario
Research Site
Bowmanville, Ontario, Canada, L1C 1P6
Research Site
Brampton, Ontario, Canada, L6T 3J1
Research Site
Burlington, Ontario, Canada, L7R 4B7
Research Site
Hamilton, Ontario, Canada, L8N 1Y2
Research Site
London, Ontario, Canada, N6A 4V2
Research Site
Mississauga, Ontario, Canada, L5M 2V8
Research Site
Newmarket, Ontario, Canada, L3Y 3R7
Research Site
Ottawa, Ontario, Canada, K1S 1C2
Research Site
St Catharines, Ontario, Canada, L2N 7E4
Research Site
Toronto, Ontario, Canada, M9B 6H8
Research Site
Toronto, Ontario, Canada, M5G 1X5
Canada, Quebec
Research Site
Laval, Quebec, Canada, H7T 2P5
Research Site
Montreal, Quebec, Canada, H3T 1E2
Research Site
Montreal, Quebec, Canada, H2L 1S6
Research Site
Montreal, Quebec, Canada, H3Z 2Z3
Research Site
Rimouski, Quebec, Canada, G5L 8W1
Research Site
Saint Leonard, Quebec, Canada, H1R 1X8
Research Site
Saint-Eustache, Quebec, Canada, J7P 4J2
Canada, Saskatchewan
Research Site
Saskatoon, Saskatchewan, Canada, S7K 0H6
Canada
Research Site
Quebec, Canada, G1V 3M7
Sponsors and Collaborators
Amgen
Wyeth is now a wholly owned subsidiary of Pfizer
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
No publications provided

Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT00654368     History of Changes
Other Study ID Numbers: 20070301
Study First Received: April 3, 2008
Results First Received: February 10, 2014
Last Updated: July 14, 2014
Health Authority: Canada: Institutional Review Board

Keywords provided by Amgen:
Amgen

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Methotrexate
TNFR-Fc fusion protein
Immunoglobulin G
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
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

ClinicalTrials.gov processed this record on October 16, 2014