Moderate Rheumatoid Arthritis (RA) With Etanercept (Enbrel)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT01313208
First received: March 10, 2011
Last updated: May 7, 2014
Last verified: May 2014
  Purpose

This study is designed to evaluate the effectiveness of adding etanercept to disease modifying anti-rheumatic drug (DMARD) therapy in patients with moderately active Rheumatoid Arthritis (RA).


Condition Intervention Phase
Rheumatoid Arthritis
Drug: etanercept
Drug: Placebo
Drug: DMARD Therapy
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Etanercept in Subjects With Moderately Active Rheumatoid Arthritis Despite DMARD Therapy

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • Percentage of Participants Achieving DAS28 Low Disease Activity at Week 12 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]

    Low disease activity is defined by a disease activity score (28 joint) calculated using the C-reactive protein formula (DAS28-CRP) of less than 3.2. 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; • C-Reactive Protein (CRP) level • Patient's global assessment of disease activity measured on a likert scale from 0 (no activity at all) to 10 (worst activity).

    The DAS28 score ranges from zero up to approximately ten. DAS28 scores above 5.1 indicate high disease activity.



Secondary Outcome Measures:
  • Percentage of Participants Achieving DAS28 Remission at Week 12 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]

    Remission is defined by a DAS28 score less than 2.6. 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;
    • C-reactive protein (CRP)
    • Patient's global assessment of disease activity measured on a likert scale from 0 (no activity at all) to 10 (worst activity).

    The DAS28 score ranges from zero to ten. DAS28 above 5.1 indicates high disease activity.


  • Percentage of Participants Achieving DAS28 Low Disease Activity at All Other Timepoints [ Time Frame: Baseline and Weeks 2, 4, 8, 16, 20 and 24 ] [ Designated as safety issue: No ]

    Low disease activity is defined by a disease activity score (28 joint) calculated using the C-reactive protein formula (DAS28-CRP) of less than 3.2. 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;
    • C-Reactive Protein (CRP) level
    • Patient's global assessment of disease activity measured on a likert scale from 0 (no activity at all) to 10 (worst activity).

    The DAS28 score ranges from zero up to approximately ten. DAS28 scores above 5.1 indicate high disease activity.


  • Percentage of Participants Achieving DAS28 Remission at All Other Timepoints [ Time Frame: Baseline and Weeks 2, 4, 8, 16, 20 and 24 ] [ Designated as safety issue: No ]

    Remission is defined by a DAS28 score less than 2.6. 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;
    • C-reactive protein (CRP)
    • Patient's global assessment of disease activity measured on a likert scale from 0 (no activity at all) to 10 (worst activity).

    The DAS28 score ranges from zero to ten. A DAS28 above 5.1 indicates high disease activity.


  • Percentage of Participants With American College of Rheumatology (ACR) 20 Response at Each Timepoint [ Time Frame: Baseline and Weeks 2, 4, 8, 12, 16, 20 and 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: ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); ◦ Patient's global assessment of disease activity (measured on a likert scale from 0 to 10); ◦ Physician's global assessment of disease activity (measured on a likert scale from 0 to 10); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]); ◦ C-Reactive Protein level.

  • Percentage of Participants With American College of Rheumatology (ACR) 50 Response at Each Timepoint [ Time Frame: Baseline and Weeks 2, 4, 8, 12, 16, 20 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:

      • Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]);
      • Patient's global assessment of disease activity (measured on a likert scale from 0 to 10);
      • Physician's global assessment of disease activity (measured on a likert scale from 0 to 10);
      • Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]);
      • C-reactive protein (CRP) level.

  • Percentage of Participants With American College of Rheumatology (ACR) 70 Response at Each Timepoint [ Time Frame: Baseline and Weeks 2, 4, 8, 12, 16, 20 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:

      • Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]);
      • Patient's global assessment of disease activity (measured on a likert scale from 0 to 10);
      • Physician's global assessment of disease activity (measured on a likert scale from 0 to 10);
      • Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]);
      • C-reactive protein (CRP) level.

  • Percentage of Participants With RAPID3 Remission or Low Severity at Each Time Point [ Time Frame: Baseline and Weeks 4, 12, and 24 ] [ Designated as safety issue: No ]
    The Multi-Dimensional Health Assessment Questionnaire (MDHAQ) is adapted from the standard HAQ and is used for the computation of the Routine Assessment of Patient Index Data 3 (RAPID3). The RAPID 3 includes the 3 Core Data Set measures of physical function, pain, and patient global estimate. The score for physical function ranges from 0 to 10 and is calculated by adding the ten activities of daily living, each scored from 0 to 3 by the patient (0="without any difficulty", 1="with some difficulty", 2="with much difficulty", and 3="unable to do") and dividing the total raw score by 3. Pain and global estimate of health are measured on a likert scale from 0 to 10, both scored 0 (best) to 10 (worst). The three 0-10 scores for physical function, pain, and global assesment of health are added together for a composite score of 0 to 30. The RAPID3 composite score includes 4 categories: High Severity > 12, Moderate Severity = 6.1 - 12, Low severity = 3.1 - 6, and Remission ≤ 3.

  • Percentage of Participants Achieving Count Remission at Each Time Point [ Time Frame: Baseline and Weeks 2, 4, 8, 12, 16, 20 and 24 ] [ Designated as safety issue: No ]
    Count remission is achieved when a participant satisfies all of the following at any given time point: - 68 tender joint count ≤ 1, - 66 swollen joint count ≤ 1, - C-reactive protein (CRP) (in mg/dL) ≤1, and - patient global assessment of disease activity ≤ 1 (measured on a likert scale from 0 to 10 ranging from "no activity at all" to "worst activity imaginable").

  • Percentage of Participants Achieving CDAI Remission at Each Time Point [ Time Frame: Baseline and Weeks 2, 4, 8, 12, 16, 20 and 24 ] [ Designated as safety issue: No ]

    The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the:

    • 28 tender joint count (TJC),
    • 28 swollen joint count (SJC),
    • Patient's Global Assessment of Disease Activity measured on a likert scale from 0 to 10, where 0 = lowest disease activity and 10 = highest;
    • Physician's Global Assessment of Disease Activity measured on a Likert scale from 0 to 10, where 0 = lowest disease activity and 10 = highest.

    The CDAI score ranges from 0-76 where lower scores indicate less disease activity. CDAI remission is defined as a score ≤ 2.8.


  • Percentage of Participants Achieving CDAI Low Disease Activity at Each Time Point [ Time Frame: Baseline and Weeks 2, 4, 8, 12, 16, 20 and 24 ] [ Designated as safety issue: No ]

    The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the:

    • 28 tender joint count (TJC),
    • 28 swollen joint count (SJC),
    • Patient's Global Assessment of Disease Activity measured on a Likert scale form 0 to 10, where 0 = lowest disease activity and 10 = highest;
    • Physician's Global Assessment of Disease Activity -measured on a Likert scale from 0 to 10, where 0 = lowest disease activity and 10 = highest. The CDAI score ranges from 0 to 76 where lower scores indicate less disease activity. CDAI low disease activity is defined as a score ≤ 10.

  • Clinical Disease Activity Index (CDAI) Score at Each Time Point [ Time Frame: Baseline and Weeks 2, 4, 8, 12, 16, 20 and 24 ] [ Designated as safety issue: No ]

    The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the:

    • 28 tender joint count (TJC),
    • 28 swollen joint count (SJC),
    • Patient's Global Assessment of Disease Activity measured on a Likert scale from 0 to 10 where 0 = lowest disease activity and 10 = highest;
    • Physician's Global Assessment of Disease Activity (measured on a Likert scale from 0 to 10 where 0 = lowest disease activity and 10 = highest).

    The CDAI score ranges from 0 to 76 where lower scores indicate less disease activity.


  • Percentage of Participants Achieving SDAI Remission at Each Time Point [ Time Frame: Baseline and Weeks 2, 4, 8, 12, 16, 20 and 24 ] [ Designated as safety issue: No ]

    The simplified disease activity index (SDAI) is a composite measure that sums the total number of:

    • 28 tender joint counts,
    • 28 swollen joint counts,
    • Patient's Global Assessment of Disease Activity measured on a Likert scale from 0 to 10 where 0= lowest disease activity and 10 = highest;
    • Physician's Global Assessment of Disease Activity measured on a Likert scale from 0 to 10, where 0 = lowest disease activity and 10 = highest, and
    • C-reactive protein (CRP) in mg/dL.

    The SDAI score ranges from 0 to approximately 86 where lower scores indicate less disease activity. SDAI remission is defined as a score ≤ 3.3.


  • Percentage of Participants Achieving SDAI Low Disease Activity at Each Time Point [ Time Frame: Baseline and Weeks 2, 4, 8, 12, 16, 20 and 24 ] [ Designated as safety issue: No ]
    The simplified disease activity index (SDAI) is a composite measure that sums the total number of: - 28 tender joint counts, - 28 swollen joint counts, - Patient's Global Assessment of Disease Activity measured on a Likert scale from 0 to 10 where 0 = lowest disease activity and 10 = highest; - Physician's Global Assessment of Disease Activity measured on a Likert scale from 0 to 10 where 0 = lowest disease activity and 10 = highest, and - C-reactive protein (CRP) in mg/dL. The SDAI score ranges from 0 to approximately 86 where lower scores indicate less disease activity. SDAI low disease activity is defined as a score ≤ 11.

  • Simplified Clinical Disease Activity Index (SDAI) Score at Each Time Point [ Time Frame: Baseline and Weeks 2, 4, 8, 12, 16, 20 and 24 ] [ Designated as safety issue: No ]

    The simplified disease activity index (SDAI) is a composite measure that sums the total number of:

    • 28 tender joint counts,
    • 28 swollen joint counts,
    • Patient's Global Assessment of Disease Activity measured on a Likert scale from 0 to 10, where 0 = lowest disease activity and 10 = highest;
    • Physician's Global Assessment of Disease Activity measured on a Likert scale from 0 to 10, where 0 = lowest disease activity and 10 = highest, and
    • C-reactive protein (CRP) in mg/dL.

    The SDAI score ranges from 0 to approximately 86 where lower scores indicate less disease activity.


  • Tender 28-Joint Count (TJC28) at Each Time Point [ Time Frame: Baseline and Weeks 2, 4, 8, 12, 16, 20 and 24 ] [ Designated as safety issue: No ]
    Twenty-eight joints were assessed and classified as tender/not tender by pressure and joint manipulation on physical examination.

  • Swollen 28-Joint Count (SJC28) at Each Time Point [ Time Frame: Baseline and Weeks 2, 4, 8, 12, 16, 20 and 24 ] [ Designated as safety issue: No ]
    Twenty-eight joints were assessed and classified as swollen/not swollen by pressure and joint manipulation on physical examination.

  • Patient Global Assessment of Joint Pain at Each Time Point [ Time Frame: Baseline and Weeks 2, 4, 8, 12, 16, 20 and 24 ] [ Designated as safety issue: No ]
    The severity of the participant's joint pain was assessed using a visual analog scale (VAS). The participant was asked to draw a mark through a 100 mm horizontal line to indicate how much pain they were experiencing "today", from '0' (no pain at all) on the left end of the line to 100 (worst pain imaginable) on the right end of the line.

  • Patient's Global Assessment of Disease Activity at Each Time Point [ Time Frame: Baseline and Weeks 2, 4, 8, 12, 16, 20 and 24 ] [ Designated as safety issue: No ]
    The participant's global assessment of their arthritis disease activity was assessed by the participant circling a number from 0 to 10 on a horizontal Likert scale ranging from "No Activity at All" (score = 0) to "Worst Activity Imaginable" (score = 10).

  • Physician Global Assessment of Disease Activity at Each Time Point [ Time Frame: Baseline and Weeks 2, 4, 8, 12, 16, 20 and 24 ] [ Designated as safety issue: No ]
    The global assessment of the participant's arthritis was assessed by the physician circling a number from 0 to 10 on a horizontal Likert scale ranging from "No Activity at All" (score = 0) to "Worst Activity Imaginable" (score = 10).

  • Change From Baseline in the Disability Index of the Health Assessment Questionnaire (HAQ-DI) at Each Time Point [ Time Frame: Baseline and Weeks 2, 4, 8, 12, 16, 20 and 24 ] [ Designated as safety issue: No ]
    The HAQ-DI asks about the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and errands and chores). Responses in each functional area 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 to 3, where zero represents no disability and three very severe, high-dependency disability.

  • C-reactive Protein Levels at Each Time Point [ Time Frame: Baseline and Weeks 2, 4, 8, 12, 16, 20 and 24 ] [ Designated as safety issue: No ]
    C-Reactive Protein (CRP) was measured from blood samples by a central laboratory as a marker for inflammation.

  • Short Form 36 Health Survey (SF-36) Physical Functioning Domain Score at Each Time Point [ Time Frame: Baseline and Weeks 4, 12 and 24 ] [ Designated as safety issue: No ]
    The SF-36 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). The individual domain scores are calculated and transformed to range from 0 to 100, with higher scores indicating a better level of functioning. The physical functioning subscale assesses limitations in physical activities because of health problems. Least Squares means are from a mixed-effect model for repeated measurements (MMRM).

  • Short Form 36 Health Survey (SF-36) Vitality Domain Score at Each Time Point [ Time Frame: Baseline and Weeks 4, 12 and 24 ] [ Designated as safety issue: No ]
    The SF-36 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). The individual domain scores are calculated and transformed to range from 0 to 100, with higher scores indicating a better level of functioning. The vitality sub-score assesses energy and fatigue. Least Squares means are from a mixed-effect model for repeated measurements (MMRM).

  • Short Form 36 Health Survey (SF-36) Role-Physical Domain Score at Each Time Point [ Time Frame: Baseline and Weeks 4, 12 and 24 ] [ Designated as safety issue: No ]
    The SF-36 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). The individual domain scores are calculated and transformed to range from 0 to 100, with higher scores indicating a better level of functioning. The role-physical subscale assesses limitations in usual role activities because of physical health problems. Least squares means are from a mixed-effect model for repeated measurements (MMRM).

  • Short Form 36 Health Survey (SF-36) Bodily Pain Domain Score at Each Time Point [ Time Frame: Baseline and Weeks 4, 12 and 24 ] [ Designated as safety issue: No ]
    The SF-36 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). The individual domain scores are calculated and transformed to range from 0 to 100, with higher scores indicating a better level of functioning (less pain). Least squares means are from a mixed-effect model for repeated measurements (MMRM).

  • Short Form 36 Health Survey (SF-36) General Health Perceptions Domain Score at Each Time Point [ Time Frame: Baseline and Weeks 4, 12 and 24 ] [ Designated as safety issue: No ]
    The SF-36 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). The individual domain scores are calculated and transformed to range from 0 to 100, with higher scores indicating a better quality of life. Least squares means are from a mixed-effect model for repeated measurements (MMRM).

  • Short Form 36 Health Survey (SF-36) Social Functioning Domain Score at Each Time Point [ Time Frame: Baseline and Weeks 4, 12 and 24 ] [ Designated as safety issue: No ]
    The SF-36 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). The individual domain scores are calculated and transformed to range from 0 to 100, with higher scores indicating a better level of functioning. The social functioning subscale assesses limitations in social activities because of physical or emotional problems. Least Squares means are from a mixed-effect model for repeated measurements (MMRM).

  • Short Form 36 Health Survey (SF-36) Role-Emotional Domain Score at Each Time Point [ Time Frame: Baseline and Weeks 4, 12 and 24 ] [ Designated as safety issue: No ]
    The SF-36 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). The individual domain scores are calculated and transformed to range from 0 to 100, with higher scores indicating a better quality of life. The role-emotional subscale assesses limitations in usual role activities because of emotional problems. Least squares means are from a mixed-effect model for repeated measurements (MMRM).

  • Short Form 36 Health Survey (SF-36) Mental Health Domain Score at Each Time Point [ Time Frame: Baseline and Weeks 4, 12 and 24 ] [ Designated as safety issue: No ]
    The SF-36 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). The individual domain scores are calculated and transformed to range from 0 to 100, with higher scores indicating a better quality of life. The mental health sub-score assesses general mental health (psychological distress and well-being). Least squares means are from a mixed-effect model for repeated measurements (MMRM).

  • Work Productivity and Activity Impairment Questionnaire (WPAI): Percent Work Time Missed (Absenteeism) at Each Time Point [ Time Frame: Baseline and Weeks 4, 12 and 24 ] [ Designated as safety issue: No ]
    This self-administered questionnaire is designed to address impairment to the work productivity and activity of participants due to rheumatoid arthritis in the past 7 days. Percent of work time missed is derived from the number of hours of work missed due to rheumatoid arthritis symptoms as a percentage of total hours that should have been worked. A higher percentage indicates more hours missed. Least squares means are from a mixed-effect model for repeated measurements (MMRM).

  • Work Productivity and Activity Impairment Questionnaire (WPAI): Percent Impairment While Working (Presenteeism) at Each Time Point [ Time Frame: Baseline and Weeks 4, 12 and 24 ] [ Designated as safety issue: No ]
    This self-administered questionnaire is designed to address impairment to the work productivity and activity of participants due to rheumatoid arthritis in the past 7 days. Percent impairment while working was derived from the participant's assessment of the degree to which rheumatoid arthritis affected their productivity while working. A higher percentage indicates greater impairment and less productivity. Least squares means are from a mixed-effect model for repeated measurements (MMRM).

  • Work Productivity and Activity Impairment Questionnaire (WPAI): Percent Activity Impairment at Each Time Point [ Time Frame: Baseline and Weeks 4, 12 and 24 ] [ Designated as safety issue: No ]
    This self-administered questionnaire is designed to address impairment to the work productivity and activity of participants due to rheumatoid arthritis. Percent activity impairment is derived from the patient's assessment of the degree to which rheumatoid arthritis affected their regular daily activities. A higher percentage indicates greater impairment and less productivity. Least squares means are from a mixed-effect model for repeated measurements (MMRM).

  • Work Productivity and Activity Impairment Questionnaire (WPAI): Percent Overall Work Impairment at Each Time Point [ Time Frame: Baseline and Weeks 4, 12 and 24 ] [ Designated as safety issue: No ]
    This self-administered questionnaire is designed to address impairment to the work productivity and activity of participants due to rheumatoid arthritis in the past 7 days. Percent overall work impairment takes into account both hours missed due to rheumatoid arthritis symptoms and the participant's assessment of the degree to which rheumatoid arthritis affected their productivity while working. A higher percentage indicates greater impairment and less productivity. Least squares means are from a mixed-effect model for repeated measurements (MMRM).

  • Participant Assessment of Fatigue at Each Time Point [ Time Frame: Baseline and Weeks 2, 4, 8, 12, 16, 20 and 24 ] [ Designated as safety issue: No ]
    The participant's assessment of fatigue was collected using a single-item 100 mm visual analogue scale. The participant was asked to draw a vertical line through a horizontal line to indicate the degree of fatigue they experienced because of their condition over the past week. The horizontal line is 100 mm in length with '0' and 'no fatigue' on the left end of the line and '100' and 'extreme fatigue' on the right end of the line. Least squares means are from a mixed-effect model for repeated measurements (MMRM).

  • Medical Outcomes Study (MOS) Sleep Disturbance Scale at Each Time Point [ Time Frame: Baseline and Weeks 4, 12 and 24 ] [ Designated as safety issue: No ]
    The MOS-Sleep comprises 12 items and measures key sleep structures across 6 domains. These domains are Sleep Disturbance (4 items), Sleep Adequacy (2 items), Sleep Quantity (1 item), Daytime Somnolence (3 items), Snoring (1 item), and Shortness of Breath (1 item). Sleep Disturbance measures the ability to fall asleep and to maintain restful sleep. In MOS Sleep norm-based scoring, all scales are scored on the same metric, where 50 is the mean for the general U.S. population and 10 is the standard deviation. Higher scores indicate more severe sleep problems. Least Squares means are from a mixed-effect model for repeated measurements (MMRM).

  • Medical Outcomes Study (MOS) Sleep Shortness of Breath or Headache Scale at Each Time Point [ Time Frame: Baseline and Weeks 4, 12 and 24 ] [ Designated as safety issue: No ]
    The MOS-Sleep comprises 12 items and measures key sleep structures across 6 domains. These domains are Sleep Disturbance (4 items), Sleep Adequacy (2 items), Sleep Quantity (1 item), Daytime Somnolence (3 items), Snoring (1 item), and Awakening short of breath or with a headache, (1 item). In MOS Sleep norm-based scoring, all scales are scored on the same metric, where 50 is the mean for the general U.S. population and 10 is the standard deviation. Higher scores indicate more severe sleep problems. Least Squares means are from a mixed-effect model for repeated measurements (MMRM).

  • Medical Outcomes Study (MOS) Sleep Snoring Scale at Each Time Point [ Time Frame: Baseline and Weeks 4, 12 and 24 ] [ Designated as safety issue: No ]
    The MOS-Sleep comprises 12 items and measures key sleep structures across 6 domains. These domains are Sleep Disturbance (4 items), Sleep Adequacy (2 items), Sleep Quantity (1 item), Daytime Somnolence (3 items), Snoring (1 item), and Shortness of Breath (1 item). In MOS Sleep norm-based scoring, all scales are scored on the same metric, where 50 is the mean for the general U.S. population and 10 is the standard deviation. Higher scores indicate more severe sleep problems. Least Squares means are from a mixed-effect model for repeated measurements (MMRM).

  • Medical Outcomes Study (MOS) Sleep Adequacy Scale at Each Time Point [ Time Frame: Baseline and Weeks 4, 12 and 24 ] [ Designated as safety issue: No ]
    The MOS-Sleep comprises 12 items and measures key sleep structures across 6 domains. These domains are Sleep Disturbance (4 items), Sleep Adequacy (2 items), Sleep Quantity (1 item), Daytime Somnolence (3 items), Snoring (1 item), and Awakening short of breath or with a headache, (1 item). Sleep Adequacy measures sleep sufficiency in terms of whether the participant sleeps enough to provide restoration of wakefulness. In MOS Sleep norm-based scoring, all scales are scored on the same metric, where 50 is the mean for the general U.S. population and 10 is the standard deviation. For sleep adequacy a higher score indicates better sleep quality. Least Squares means are from a mixed-effect model for repeated measurements (MMRM).

  • Medical Outcomes Study (MOS) Sleep Daytime Somnolence Scale at Each Time Point [ Time Frame: Baseline and Weeks 4, 12 and 24 ] [ Designated as safety issue: No ]
    The MOS-Sleep comprises 12 items and measures key sleep structures across 6 domains. These domains are Sleep Disturbance (4 items), Sleep Adequacy (2 items), Sleep Quantity (1 item), Daytime Somnolence (3 items), Snoring (1 item), and Awakening short of breath or with a headache, (1 item). Daytime somnolence measures drowsiness or sleepiness during the day. In MOS Sleep norm-based scoring, all scales are scored on the same metric, where 50 is the mean for the general U.S. population and 10 is the standard deviation. Higher scores indicate more severe sleep problems. Least Squares means are from a mixed-effect model for repeated measurements (MMRM).

  • Medical Outcomes Study (MOS) Sleep Problems Index I at Each Time Point [ Time Frame: Baseline and Weeks 4, 12 and 24 ] [ Designated as safety issue: No ]
    The MOS-Sleep comprises 12 items and measures key sleep structures across 6 domains. These domains are Sleep Disturbance (4 items), Sleep Adequacy (2 items), Sleep Quantity (1 item), Daytime Somnolence (3 items), Snoring (1 item), and Awakening short of breath or with a headache, (1 item). The scale also produces two indices. The Sleep Problems Index-I is drawn from 6 items in the four domains including Sleep Disturbance (2 items), Sleep Adequacy (2 items), Shortness of Breath (1 item), and Daytime Somnolence (1 item). In MOS Sleep norm-based scoring, all scales are scored on the same metric, where 50 is the mean for the general U.S. population and 10 is the standard deviation. Higher scores indicate more severe sleep problems. Least Squares means are from a mixed-effect model for repeated measurements (MMRM).

  • Medical Outcomes Study (MOS) Sleep Problems Index II at Each Time Point [ Time Frame: Baseline and Weeks 4, 12 and 24 ] [ Designated as safety issue: No ]
    The MOS-Sleep comprises 12 items and measures key sleep structures across 6 domains. These domains are Sleep Disturbance (4 items), Sleep Adequacy (2 items), Sleep Quantity (1 item), Daytime Somnolence (3 items), Snoring (1 item), and Awakening short of breath or with a headache, (1 item). The scale also produces two indices. Index-II uses 9 items from four domains including Sleep Disturbance (4 items), Sleep Adequacy (2 items), Shortness of Breath (1 item), and Daytime Somnolence (2 items). In MOS Sleep norm-based scoring, all scales are scored on the same metric, where 50 is the mean for the general U.S. population and 10 is the standard deviation. Higher scores indicate more severe sleep problems. Least Squares means are from a mixed-effect model for repeated measurements (MMRM).


Enrollment: 210
Study Start Date: March 2011
Study Completion Date: May 2013
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo

Participants received placebo subcutaneous injections once a week for 12 weeks and then open-label etanercept 50 mg subcutaneous injection once weekly for the next 12 weeks.

All participants continued their disease modifying anti-rheumatic drug (DMARD) treatment throughout the 24-week study period.

Drug: etanercept
Administered by subcutaneous injection once weekly.
Other Name: Enbrel
Drug: Placebo
Placebo subcutaneous injection
Drug: DMARD Therapy
Standard-of-care DMARD therapy, including methotrexate, sulfasalazine, leflunomide, minocycline, and/or hydroxychloroquine
Experimental: Etanercept

Participants received etanercept 50 mg subcutaneous injection once weekly for 12 weeks and then open-label etanercept 50 mg subcutaneous injection for the next 12 weeks.

All participants continued their DMARD treatment throughout the 24-week study period.

Drug: etanercept
Administered by subcutaneous injection once weekly.
Other Name: Enbrel
Drug: DMARD Therapy
Standard-of-care DMARD therapy, including methotrexate, sulfasalazine, leflunomide, minocycline, and/or hydroxychloroquine

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female ≥18 and ≤80 years of age at time of screening
  • Diagnosed with rheumatoid arthritis as determined by meeting 1987 American College of Rheumatology (ACR) classification criteria and has had rheumatoid arthritis for at least 6 months
  • Moderate rheumatoid arthritis during screening, as defined by a disease activity score (28 joint) calculated using the C-reactive protein formula (DAS28-CRP) > 3.2 and ≤ 5.1
  • Active rheumatoid arthritis defined as ≥ 3 swollen joints (out of 28 joints examined) and ≥ 3 tender/painful joints (out of 28 joints examined) at screening and baseline. (A full 66/68 count joint count will be performed at baseline, but only joints in the 28-count joint count will be considered for eligibility. The 28-joint count consists of the finger joints excluding the distal interphalangeal joints, the wrists, elbows, shoulders, and knees)
  • Must be currently taking a DMARD such as methotrexate, sulfasalazine, leflunomide, minocycline, and/or hydroxychloroquine

Exclusion Criteria:

  • Prosthetic joint infection within 5 years of screening or native joint infection within 1 year of screening
  • Class IV rheumatoid arthritis according to ACR revised response criteria
  • Any active infection (including chronic or localized infections) for which anti-infectives were indicated within 28 days prior to first investigational product dose
  • Previously used more than one experimental biologic DMARD. Patient with prior use of no more than one experimental biologic is permitted if the subject received no more than 8 weeks of treatment. The use of the experimental biologic must not have occurred within 2 months of the first dose of investigational product
  • Previously used more than one commercially available biologic DMARD. Subject with prior use of no more than one commercially available biologic is permitted if the patient received no more than 8 weeks of treatment and did not discontinue because of lack of effect. The use of the biologic must not have occurred within 2 months of the first dose of investigational product. Acceptable prior use of biologics include the following examples:
  • No more than 4 injections of adalimumab
  • No more than 8 (50 mg) injections of etanercept
  • No more than 2 infusions of infliximab
  • No more than 2 infusions of abatacept
  • Additional 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: NCT01313208

  Show 47 Study Locations
Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
No publications provided

Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT01313208     History of Changes
Other Study ID Numbers: 20070561
Study First Received: March 10, 2011
Results First Received: May 7, 2014
Last Updated: May 7, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

Keywords provided by Amgen:
RA
Enbrel
DMARD
Joint Count
Rheumatoid Arthritis
Etanercept
disease modifying anti-rheumatic drug

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

ClinicalTrials.gov processed this record on October 19, 2014