Study of Apremilast to Evaluate the Safety and Effectiveness for Patients With Rheumatoid Arthritis

This study has been terminated.
(Study is terminated due to lack of efficacy)
Sponsor:
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT01285310
First received: November 19, 2010
Last updated: August 13, 2014
Last verified: August 2014
  Purpose

The purpose of this study is to determine whether Apremilast is safe and effective in the treatment of patients with rheumatoid arthritis, specifically in improving signs and symptoms of rheumatoid arthritis (tender and swollen joints, pain, physical function and structure) in treated patients who have had an inadequate response to Methotrexate.


Condition Intervention Phase
Rheumatoid Arthritis
Drug: Apremilast 30 mg
Drug: Apremilast 20 mg
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study, To Compare the Efficacy and Safety of Two Doses of Apremilast (CC-10004) in Subjects With Active Rheumatoid Arthritis Who Have Had an Inadequate Response to Methotrexate

Resource links provided by NLM:


Further study details as provided by Celgene Corporation:

Primary Outcome Measures:
  • Percentage of Participants With an American College of Rheumatology 20% Improvement (ACR 20) Response at Week 16 [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]

    Percentage of participants with an American College of Rheumatology 20% Improvement (ACR 20) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met:

    • ≥ 20% improvement in 68 tender joint count;
    • ≥ 20% improvement in 66 swollen joint count; and
    • ≥ 20% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index ([HAQ-DI]); C-Reactive Protein.


Secondary Outcome Measures:
  • Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 16 [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]
    The Health Assessment Questionnaire - Disability Index (HAQ-DI) was a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.

  • Percentage of Participants With an American College of Rheumatology 20% Improvement (ACR 20) Response at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]

    Percentage of participants with an American College of Rheumatology 20% Improvement (ACR 20) response. A participant was a responder if the following 3 criteria for improvement from baseline were met:

    • ≥ 20% improvement in 68 tender joint count;
    • ≥ 20% improvement in 66 swollen joint count; and
    • ≥ 20% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index ([HAQ-DI]); C-Reactive Protein

  • Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    The Health Assessment Questionnaire - Disability Index (HAQ-DI) is a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.

  • Change From Baseline in the Medical Outcome Study Short Form 36-item (SF-36) Physical Functioning Domain at Week 16 [ Time Frame: Baseline and Week 16 ] [ 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). The concepts measured by the SF-36 are not specific to any age, disease, or treatment group, allowing comparison of relative burden of different diseases and the relative benefit of different treatments. Norm-based scores were used in analyses, calibrated so that 50 is the average score and the standard deviation equals 10. Higher scores indicate a higher level of functioning. The physical functioning domain assesses limitations in physical activities because of health problems. A positive change from baseline score indicates an improvement.

  • Change From Baseline in the Clinical Disease Activity Index (CDAI) at Week 16 [ Time Frame: Baseline and Week 16 ] [ 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),
    • Subject's Global Assessment of Disease Activity measured on a 100 mm visual analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest;
    • Physician's Global Assessment of Disease Activity -measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest.

    The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI:

    Remission: ≤ 2.8; Low Disease Activity: > 2.8 and ≤ 10; Moderate Disease Activity: > 10 and ≤ 22; High Disease Activity: > 22


  • Percentage of Participants Who Achieve Low Disease Activity or Remission Based on the Clinical Disease Activity Index (CDAI) ≤ 10 at Week 16 [ Time Frame: Baseline and Week 16 ] [ 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),
    • Subject's Global Assessment of Disease Activity measured on a 100 mm visual analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest;
    • Physician's Global Assessment of Disease Activity -measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest.

    The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI:

    Remission: ≤ 2.8; Low Disease Activity: > 2.8 and ≤ 10; Moderate Disease Activity: > 10 and ≤ 22; High Disease Activity: > 22


  • Change From Baseline in Disease Activity Score 28 (DAS28) (Using C-Reactive Protein) (CRP) at Week 16 [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]

    The DAS28 measures the severity of disease at a specific time and is derived from the following variables:

    • 28 tender joint count (TJC28)
    • 28 swollen joint count (SJC28), which do not include the distal interphalangeal (DIP) joints, the hip joint, or the joints below the knee;
    • C-reactive protein (CRP)
    • Subject's global assessment of disease activity (SGA )

    DAS28 values range from 2.0 to 10.0 while higher values mean a higher disease activity.

    A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission.


  • Percentage Change From Baseline in the Tender Joint Count at Week 16 [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]
    Joint tenderness is the presence of pain in a joint when pressure is applied by the examiner to elicit tenderness. The 68 tender joint count evaluates the following joints: upper-temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, meta-carpophalangeal, proximal interphalangeal and distal interphalangeal; lower: hip, knee, ankle, midtarsal, metatarsophalangeal and proximal interphalangeal.

  • Percentage Change From Baseline in the Swollen Joint Count at Week 16 [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]
    Joint swelling is soft tissue swelling that is detectable along the joint margins and is assessed by inspection and direct palpation of the joint, by the examiner. The ACR 66 swollen joint count evaluates the following joints: upper-temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, metacarpophalangeal, proximal interphalangeal and distal interphalangeal; lower: knee, ankle, midtarsal, metatarsophalangeal and proximal interphalangeal.

  • Percentage Change From Baseline in the Subject Assessment of Pain at Week 16 [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]
    The Subject Assessment of Pain was measured asking the participant to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents "no pain," and the right-hand boundary (score = 100 mm) represents "pain as severe as can be imagined." The distance from the mark to the left-hand boundary was recorded in millimeters.

  • Percentage Change From Baseline in the Subject Global Assessment of Disease Activity at Week 16 [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]
    The Subject Global Assessment of Disease Activity was measured asking the participant to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents " lowest disease activity," and the right-hand boundary (score = 100 mm) represents " highest disease activity." The distance from the mark to the left-hand boundary was recorded in millimeters.

  • Percentage Change From Baseline in the Physician Global Assessment of Disease Activity at Week 16 [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]
    The Physician Global Assessment of Disease Activity was measured asking the physician to assess the subject's current arthritis disease activity by placing a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents " lowest disease activity," and the right-hand boundary (score = 100 mm) represents " highest disease activity." The distance from the mark to the left-hand boundary was recorded in millimeters.

  • Percentage Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 16 [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]
    The Health Assessment Questionnaire - Disability Index (HAQ-DI) was a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.

  • Percentage Change From Baseline in the High Sensitivity C-Reactive Protein (CRP) at Week 16 [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]
    C-Reactive Protein (CRP) is a substance produced by the liver that increases in the presence of inflammation in the body. An elevated CRP level is identified with blood tests and is considered a non-specific "marker" for disease.

  • Percentage Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Week 16 [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]

    The erythrocyte sedimentation rate (ESR) is a blood test that can reveal inflammatory activity. The subject's blood is placed in a tall, thin tube, red erythrocytes gradually settle to the bottom. Inflammation can cause the cells to clump together. Because these clumps of cells are denser than individual cells, they settle to the bottom more quickly.

    The ESR test measures the distance red blood cells fall in a test tube in one hour. The farther the red blood cells have descended, the greater the inflammatory response.


  • Change From Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 16 [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]

    The FACIT-Fatigue scale was a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue.

    A positive change from baseline score indicates an improvement.


  • Percentage of Participants Who Achieve an Improvement of ≥ 0.22 Units From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 16 [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]
    The Health Assessment Questionnaire - Disability Index (HAQ-DI) was a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.

  • Percentage of Participants Who Achieve an Improvement of at Least 4 Units From Baseline in the Functional Assessment of Chronic Illness Therapy -Fatigue (FACIT-Fatigue) at Week 16 [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]

    The FACIT-Fatigue scale was a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue.

    A positive change from baseline score indicates an improvement.


  • Percentage of Participants Who Achieve the European League Against Rheumatism (EULAR) Response Criteria Using CRP at Week 16 [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]

    EULAR response criteria classify each participant as a good, moderate or non-responder to treatment based on the degree of improvement from baseline and the level of disease activity at the endpoint. EULAR response is derived using the individual subject's DAS28 as the measure of severity of disease.

    Good or moderate response is defined as follows: Good response: DAS28 at the time point ≤ 3.2 and improvement from baseline > 1.2 Moderate response: DAS28 at the time point > 3.2 and improvement from baseline > 1.2, or DAS28 at the time point ≤ 5.1 and improvement from baseline > 0.6 and ≤ 1.2


  • Percentage of Participants With an American College of Rheumatology 50% Improvement (ACR 50) Response at Week 16 [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]

    Percentage of participants with an American College of Rheumatology 50% Improvement (ACR50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met:

    • ≥ 50% improvement in 68 tender joint count;
    • ≥ 50% improvement in 66 swollen joint count; and
    • ≥ 50% improvement in at least 3 of the 5 following parameters:

    Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [(HAQ-DI)]); C-Reactive Protein.


  • Percentage of Participants With an American College of Rheumatology 70% Improvement (ACR 70) Response at Week 16 [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]

    Percentage of participants with an American College of Rheumatology 70% Improvement (ACR70) response. A participant was a responder if the following 3 criteria for improvement from baseline were met:

    • ≥ 70% improvement in 68 tender joint count;
    • ≥ 70% improvement in 66 swollen joint count; and
    • ≥ 70% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index ([HAQ-DI]); C-Reactive Protein

  • Percentage of Participants With an American College of Rheumatology 50% Improvement (ACR 50) Response at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]

    Percentage of participants with an American College of Rheumatology 50% Improvement (ACR 50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met:

    • ≥ 50% improvement in 68 tender joint count;
    • ≥ 50% improvement in 66 swollen joint count; and
    • ≥ 50% improvement in at least 3 of the 5 following parameters:

    Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [(HAQ-DI)]); C-Reactive Protein.


  • Percentage of Participants With an American College of Rheumatology 70% Improvement (ACR 70) Response at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]

    Percentage of participants with an American College of Rheumatology 70% Improvement (ACR 70) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met:

    • ≥ 70% improvement in 68 tender joint count;
    • ≥ 70% improvement in 66 swollen joint count; and
    • ≥ 70% improvement in at least 3 of the 5 following parameters:

    Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [(HAQ-DI)]); C-Reactive Protein.


  • Change From Baseline in the Medical Outcome Study Short Form 36-item (SF-36) Physical Functioning Domain 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, calibrated so that 50 is the average score and the standard deviation equals 10. Higher scores indicate a higher level of functioning. The physical functioning domain assesses limitations in physical activities because of health problems. A positive change from Baseline score indicates an improvement.

  • Change From Baseline in the Clinical Disease Activity Index (CDAI) at Week 24 [ Time Frame: Baseline and Week 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),
    • Subject's Global Assessment of Disease Activity measured on a 100 mm visual analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest;
    • Physician's Global Assessment of Disease Activity -measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest.

    The CDAI score ranges from 0-76 where lower scores indicate less disease activity.The following thresholds of disease activity have been defined for the CDAI:

    Remission: ≤ 2.8; Low Disease Activity: > 2.8 and ≤ 10; Moderate Disease Activity: > 10 and ≤ 22; High Disease Activity: > 22


  • Percentage of Participants Who Achieve Low Disease Activity or Remission Based on the Clinical Disease Activity Index (CDAI) ≤ 10 at Week 24 [ Time Frame: Baseline and Week 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),
    • Subject's Global Assessment of Disease Activity measured on a 100 mm visual analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest;
    • Physician's Global Assessment of Disease Activity -measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest.

    The CDAI score ranges from 0-76 where lower scores indicate less disease activity.The following thresholds of disease activity have been defined for the CDAI:

    Remission: ≤ 2.8; Low Disease Activity: > 2.8 and ≤ 10; Moderate Disease Activity: > 10 and ≤ 22; High Disease Activity: > 22


  • Change From Baseline in Disease Activity Score 28 (DAS28) Using CRP at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]

    The DAS28 measures the severity of disease at a specific time and is derived from the following variables:

    • 28 tender joint count
    • 28 swollen joint count, which do not include the DIP joints, the hip joint, or the joints below the knee;
    • C-reactive protein (CRP)
    • Subject's Global Assessment of Disease Activity.

    DAS28 values range from 2.0 to 10.0 while higher values mean a higher disease activity.

    A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission.


  • Percentage Change From Baseline in the Tender Joint Count at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    Joint tenderness is the presence of pain in a joint when pressure is applied by the examiner to elicit tenderness. The 68 tender joint count evaluates the following joints: upper-temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, meta-carpophalangeal, proximal interphalangeal and distal interphalangeal; lower: hip, knee, ankle, midtarsal, metatarsophalangeal and proximal interphalangeal.

  • Percentage Change From Baseline in the Swollen Joint Count at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    Joint swelling is soft tissue swelling that is detectable along the joint margins and is assessed by inspection and direct palpation of the joint, by the examiner. The ACR 66 swollen joint count evaluates the following joints: upper-temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, metacarpophalangeal, proximal interphalangeal and distal interphalangeal; lower: knee, ankle, midtarsal, metatarsophalangeal and proximal interphalangeal.

  • Percentage Change From Baseline in the Subject Assessment of Pain at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    The Subject Assessment of Pain was measured asking the participant to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents "no pain," and the right-hand boundary (score = 100 mm) represents "pain as severe as can be imagined." The distance from the mark to the left-hand boundary was recorded in millimeters.

  • Percentage Change From Baseline in the Subject Global Assessment of Disease Activity at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    The Subject Global Assessment of Disease Activity was measured asking the participant to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents " lowest disease activity," and the right-hand boundary (score = 100 mm) represents " highest disease activity." The distance from the mark to the left-hand boundary was recorded in millimeters.

  • Percentage Change From Baseline in the Physician Global Assessment of Disease Activity at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    The Physician Global Assessment of Disease Activity was measured asking the physician to assess the subject's current arthritis disease activity by placing a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents " lowest disease activity," and the right-hand boundary (score = 100 mm) represents " highest disease activity." The distance from the mark to the left-hand boundary was recorded in millimeters.

  • Percentage Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    The Health Assessment Questionnaire - Disability Index (HAQ-DI) was a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.

  • Percentage Change From Baseline in the High Sensitivity C-Reactive Protein (CRP) at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    C-Reactive Protein (CRP) is a substance produced by the liver that increases in the presence of inflammation in the body. An elevated CRP level is identified with blood tests and is considered a non-specific "marker" for disease.

  • Percentage Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]

    The erythrocyte sedimentation rate (ESR) is a blood test that can reveal inflammatory activity. The subject's blood is placed in a tall, thin tube, red erythrocytes gradually settle to the bottom. Inflammation can cause the cells to clump together. Because these clumps of cells are denser than individual cells, they settle to the bottom more quickly.

    The ESR test measures the distance red blood cells fall in a test tube in one hour. The farther the red blood cells have descended, the greater the inflammatory response.


  • Change From Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]

    The FACIT-Fatigue scale was a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue.

    A positive change from baseline score indicates an improvement.


  • Percentage of Participants Who Achieve an Improvement of ≥ 0.22 Units From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    The Health Assessment Questionnaire - Disability Index (HAQ-DI) is a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.

  • Percentage of Participants Who Achieve an Improvement of at Least 4 Units From Baseline in the Functional Assessment of Chronic Illness Therapy -Fatigue (FACIT-Fatigue) at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]

    The FACIT-Fatigue scale is a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue.

    A positive change from baseline score indicates an improvement.


  • Percentage of Participants Who Achieve the European League Against Rheumatism (EULAR) Response Criteria Using CRP at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]

    EULAR response criteria classify each participant as a good, moderate or non-responder to treatment based on the degree of improvement from baseline and the level of disease activity at the endpoint. EULAR response is derived using the individual subject's DAS28 as the measure of severity of disease.

    Good or moderate response is defined as follows: Good response: DAS28 at the time point ≤ 3.2 and improvement from baseline > 1.2 Moderate response: DAS28 at the time point > 3.2 and improvement from baseline > 1.2, or DAS28 at the time point ≤ 5.1 and improvement from baseline > 0.6 and ≤ 1.2


  • Percentage of Participants With an American College of Rheumatology 20% Improvement (ACR 20) Response at Week 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]

    Percentage of participants with an American College of Rheumatology 20% Improvement (ACR 20) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met:

    • ≥ 20% improvement in 68 tender joint count;
    • ≥ 20% improvement in 66 swollen joint count; and
    • ≥ 20% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index ([HAQ-DI]); C-Reactive Protein.

  • Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]
    The Health Assessment Questionnaire - Disability Index (HAQ-DI) was a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.

  • Change From Baseline in the Medical Outcome Study Short Form 36-item (SF-36) Physical Functioning Domain at Week 52 [ Time Frame: Baseline and Week 52 ] [ 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, calibrated so that 50 is the average score and the standard deviation equals 10. Higher scores indicate a higher level of functioning. The physical functioning domain assesses limitations in physical activities because of health problems. A positive change from Baseline score indicates an improvement.

  • Change From Baseline in the Clinical Disease Activity Index (CDAI) at Week 52 [ Time Frame: Baseline and Week 52 ] [ 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),
    • Subject's Global Assessment of Disease Activity measured on a 100 mm visual analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest;
    • Physician's Global Assessment of Disease Activity -measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest.

    The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI:

    Remission: ≤ 2.8; Low Disease Activity: > 2.8 and ≤ 10; Moderate Disease Activity: > 10 and ≤ 22; High Disease Activity: > 22


  • Percentage of Participants Who Achieve Low Disease Activity or Remission Based on the Clinical Disease Activity Index (CDAI) ≤ 10 at Week 52 [ Time Frame: Baseline and Week 52 ] [ 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),
    • Subject's Global Assessment of Disease Activity measured on a 100 mm visual analog scale (VAS),, where 0 mm = lowest disease activity and 100 mm = highest;
    • Physician's Global Assessment of Disease Activity -measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest.

    The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI:

    Remission: ≤ 2.8; Low Disease Activity: > 2.8 and ≤ 10; Moderate Disease Activity: > 10 and ≤ 22; High Disease Activity: > 22


  • Change From Baseline in the Disease Activity Score 28 (DAS 28) Using CRP at Week 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]

    The DAS28 measures the severity of disease at a specific time and is derived from the following variables:

    • 28 tender joint count (TJC28)
    • 28 swollen joint count (SJC28), which do not include the distal interphalangeal (DIP) joints, the hip joint, or the joints below the knee;
    • C-reactive protein (CRP)
    • Subject's global assessment of disease activity (SGA).

    DAS28 values range from 2.0 to 10.0 while higher values mean a higher disease activity.

    A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission.


  • Percentage Change From Baseline in the Tender Joint Count at Week 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]
    Joint tenderness is the presence of pain in a joint when pressure is applied by the examiner to elicit tenderness. The 68 tender joint count evaluates the following joints: upper-temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, meta-carpophalangeal, proximal interphalangeal and distal interphalangeal; lower: hip, knee, ankle, midtarsal, metatarsophalangeal and proximal interphalangeal.

  • Percentage Change From Baseline in the Swollen Joint Count at Week 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]
    Joint swelling is soft tissue swelling that is detectable along the joint margins and is assessed by inspection and direct palpation of the joint, by the examiner. The ACR 66 swollen joint count evaluates the following joints: upper-temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, metacarpophalangeal, proximal interphalangeal and distal interphalangeal; lower: knee, ankle, midtarsal, metatarsophalangeal and proximal interphalangeal.

  • Percentage Change From Baseline in the Subject Assessment of Pain at Week 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]
    The Subject Assessment of Pain was measured asking the participant to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents "no pain," and the right-hand boundary (score = 100 mm) represents "pain as severe as can be imagined." The distance from the mark to the left-hand boundary was recorded in millimeters.

  • Percentage Change From Baseline in the Subject Global Assessment of Disease Activity at Week 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]
    The Subject Global Assessment of Disease Activity was measured asking the participant to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents " lowest disease activity," and the right-hand boundary (score = 100 mm) represents " highest disease activity." The distance from the mark to the left-hand boundary was recorded in millimeters.

  • Percentage Change From Baseline in the Physician Global Assessment of Disease Activity at Week 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]
    The Physician Global Assessment of Disease Activity was measured asking the physician to assess the subject's current arthritis disease activity by placing a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents " lowest disease activity," and the right-hand boundary (score = 100 mm) represents " highest disease activity." The distance from the mark to the left-hand boundary was recorded in millimeters.

  • Percentage Change From Baseline in the Health Assessment Questionnaire - Disability Index (HAQ-DI) Score at Week 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]
    The Health Assessment Questionnaire - Disability Index (HAQ-DI) was a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.

  • Percentage Change From Baseline in the High Sensitivity C-Reactive Protein (CRP) at Week 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]
    C-Reactive Protein (CRP) is a substance produced by the liver that increases in the presence of inflammation in the body. An elevated CRP level is identified with blood tests and is considered a non-specific "marker" for disease.

  • Percentage Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Week 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]

    The erythrocyte sedimentation rate (ESR) is a blood test that can reveal inflammatory activity. The subject's blood is placed in a tall, thin tube, red erythrocytes gradually settle to the bottom. Inflammation can cause the cells to clump together. Because these clumps of cells are denser than individual cells, they settle to the bottom more quickly.

    The ESR test measures the distance red blood cells fall in a test tube in one hour. The farther the red blood cells have descended, the greater the inflammatory response.


  • Change From Baseline in the FACIT-Fatigue Scale Score at Week 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]

    The FACIT-Fatigue scale was a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue.

    A positive change from baseline score indicates an improvement.


  • Percentage of Participants Who Achieve an Improvement of ≥ 0.22 Units From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]
    The Health Assessment Questionnaire - Disability Index (HAQ-DI) was a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.

  • Percentage of Participants With an American College of Rheumatology 50% Improvement (ACR 50) Response at Week 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]

    Percentage of participants with an American College of Rheumatology 50% Improvement (ACR 50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met:

    • ≥ 50% improvement in 68 tender joint count;
    • ≥ 50% improvement in 66 swollen joint count; and
    • ≥ 50% improvement in at least 3 of the 5 following parameters:

    Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [(HAQ-DI)]); C-Reactive Protein.


  • Percentage of Participants With an American College of Rheumatology 70% Improvement (ACR 70) Response at Week 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]

    Percentage of participants with an American College of Rheumatology 70% Improvement (ACR 70) response. A participant was a responder if the following 3 criteria for improvement from baseline were met:

    • ≥ 70% improvement in 68 tender joint count;
    • ≥ 70% improvement in 66 swollen joint count; and
    • ≥ 70% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index ([HAQ-DI]); C-Reactive Protein

  • Percentage of Participants Who Achieve an Improvement of at Least 4 Units From Baseline in the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) at Week 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]
    The FACIT-Fatigue scale is a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue. A positive change from baseline score indicates an improvement.

  • Percentage of Participants Who Achieve the European League Against Rheumatism (EULAR) Response Criteria Using CRP at Week 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]

    The EULAR response criteria classify each subject as a good, moderate or non-responder to treatment based on the degree of improvement from baseline and the level of disease activity at the endpoint. EULAR response is derived using the individual subject's DAS28 as the measure of severity of disease.

    Good or moderate response is defined as follows: Good response: DAS28 at the time point ≤ 3.2 and improvement from baseline > 1.2 Moderate response: DAS28 at the time point > 3.2 and improvement from baseline > 1.2, or DAS28 at the time point ≤ 5.1 and improvement from baseline > 0.6 and ≤ 1.2


  • Percentage of Participants With an American College of Rheumatology 20% Improvement (ACR 20) Response at Year 2 [ Time Frame: Baseline and Year 2 ] [ Designated as safety issue: No ]

    Percentage of participants with an American College of Rheumatology 20% Improvement (ACR 20) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met:

    • ≥ 20% improvement in 68 tender joint count;
    • ≥ 20% improvement in 66 swollen joint count; and
    • ≥ 20% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index ([HAQ-DI]); C-Reactive Protein.

    The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.


  • Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Year 2 [ Time Frame: Baseline and Year 2 ] [ Designated as safety issue: No ]

    The Health Assessment Questionnaire - Disability Index (HAQ-DI) is a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.

    The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.


  • Change From Baseline in the Medical Outcome Study Short Form 36-item (SF-36) Physical Functioning Domain at Year 2 [ Time Frame: Baseline and Year 2 ] [ Designated as safety issue: No ]

    The Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) was 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). The concepts measured by the SF-36 are not specific to any age, disease, or treatment group, allowing comparison of relative burden of different diseases and the relative benefit of different treatments. Norm-based scores were used in analyses, calibrated so that 50 is the average score and the standard deviation equals 10. Higher scores indicate a higher level of functioning. The physical functioning domain assesses limitations in physical activities because of health problems. A positive change from baseline score indicates an improvement.

    The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.


  • Change From Baseline in the Clinical Disease Activity Index (CDAI) at Year 2 [ Time Frame: Baseline and Year 2 ] [ 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),
    • Subject's Global Assessment of Disease Activity measured on a 10 mm visual analog scale (VAS), where 0 mm = lowest disease activity and 10 mm = highest;
    • Physician's Global Assessment of Disease Activity -measured on a 10 mm VAS, where 0 mm = lowest disease activity and 10 mm = highest.

    The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI:

    Remission: ≤ 2.8 Low Disease Activity: > 2.8 and ≤ 10 Moderate Disease Activity: > 10 and ≤ 22 High Disease Activity: > 22

    The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.


  • Percentage of Participants Who Achieve Low Disease Activity or Remission Based on the Clinical Disease Activity Index (CDAI) ≤ 10 at Year 2 [ Time Frame: Baseline and Year 2 ] [ 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),
    • Subject's Global Assessment of Disease Activity measured on a 10 mm visual analog scale (VAS), where 0 mm = lowest disease activity and 10 mm = highest;
    • Physician's Global Assessment of Disease Activity -measured on a 10 mm VAS, where 0 mm = lowest disease activity and 10 mm = highest.

    The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI:

    Remission: ≤ 2.8 Low Disease Activity: > 2.8 and ≤ 10 Moderate Disease Activity: > 10 and ≤ 22 High Disease Activity: > 22

    The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.


  • Change From Baseline in Disease Activity Score 28 (DAS28) (Using C-Reactive Protein) (CRP) at Year 2 [ Time Frame: Baseline and Year 2 ] [ Designated as safety issue: No ]

    The DAS 28 measures the severity of disease at a specific time and is derived from the following variables:

    • 28 tender joint count (TJC28)
    • 28 swollen joint count (SJC28), which do not include the distal interphalangeal (DIP) joints, the hip joint, or the joints below the knee;
    • C-reactive protein (CRP)
    • Subject's global assessment of disease activity (SGA ). A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission.

    DAS28 values range from 2.0 to 10.0 while higher values mean a higher disease activity.

    The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.


  • Percentage Change From Baseline in the Individual American College of Rheumatology Components at Year 2 [ Time Frame: Baseline and Year 2 ] [ Designated as safety issue: No ]

    The Individual ACR Components were defined as follows:

    1. Tender Joint Count (out of 68 joints)
    2. Swollen Joint Count (out of 66 joints)
    3. Subject Assessment of Pain (0 to 100 mm VAS)
    4. Subject Global Assessment of Disease Activity (0 to 100 mm VAS)
    5. Physician Global Assessment of Disease Activity (0 to 100 mm VAS)
    6. HAQ-DI Score
    7. Acute Phase Reactant High Sensitivity C-Reactive Protein (hsCRP, mg/dL) Erythrocyte Sedimentation Rate (ESR)

    The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.


  • Change From Baseline in the Functional Assessment of Chronic Illness Therapy -Fatigue (FACIT-Fatigue) at Year 2 [ Time Frame: Baseline and Year 2 ] [ Designated as safety issue: No ]

    The FACIT-Fatigue scale is a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue.

    A positive change from baseline score indicates an improvement.

    The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.


  • Percentage of Participants Who Achieve an Improvement of ≥ 0.22 Units From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Year 2 [ Time Frame: Baseline and Year 2 ] [ Designated as safety issue: No ]

    The Health Assessment Questionnaire - Disability Index (HAQ-DI) was a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.

    The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.


  • Percentage of Participants With an American College of Rheumatology 50% Improvement (ACR 50) Response at Year 2 [ Time Frame: Baseline and Year 2 ] [ Designated as safety issue: No ]

    Percentage of participants with an American College of Rheumatology 50% Improvement (ACR 50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met:

    • ≥ 50% improvement in 68 tender joint count;
    • ≥ 50% improvement in 66 swollen joint count; and
    • ≥ 50% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [(HAQ-DI)]); C-Reactive Protein.

    The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.


  • Percentage of Participants With an American College of Rheumatology 70% Improvement (ACR 70) Response at Year 2 [ Time Frame: Baseline and Year 2 ] [ Designated as safety issue: No ]

    Percentage of participants with an American College of Rheumatology 70% Improvement (ACR 70) response. A participant was a responder if the following 3 criteria for improvement from baseline were met:

    • ≥ 70% improvement in 68 tender joint count;
    • ≥ 70% improvement in 66 swollen joint count; and
    • ≥ 70% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index ([HAQ-DI]); C-Reactive Protein

    The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.


  • Percentage of Participants Who Achieve an Improvement of at Least 4 Units From Baseline in the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) at Year 2 [ Time Frame: Baseline and Year 2 ] [ Designated as safety issue: No ]

    The FACIT-Fatigue scale was a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue.

    The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.


  • Percentage of Participants Who Achieve the European League Against Rheumatism (EULAR) Response Criteria Using CRP at Year 2 [ Time Frame: Baseline and Year 2 ] [ Designated as safety issue: No ]

    EULAR response criteria classify each participant as a good, moderate or non-responder to treatment based on the degree of improvement from baseline and the level of disease activity at the endpoint. EULAR response is derived using the individual subject's DAS28 as the measure of severity of disease.

    Good or moderate response is defined as follows: Good response: DAS28 at the time point ≤ 3.2 and improvement from baseline > 1.2 Moderate response: DAS28 at the time point > 3.2 and improvement from baseline > 1.2, or DAS28 at the time point ≤ 5.1 and improvement from baseline > 0.6 and ≤ 1.2

    The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.



Enrollment: 237
Study Start Date: December 2010
Study Completion Date: September 2012
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Apremilast 30 mg

Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo-controlled phase and continued to receive 30 mg apremilast tablets twice daily (BID) for up to Week 52 in the active treatment.

At week 52, participants were given the option to remain on active treatment for 1 additional year (extension phase) as assigned during the active treatment phase.

Drug: Apremilast 30 mg
Other Names:
  • CC-10004
  • Otezla
Experimental: Apremilast 20 mg

Participants initially randomized to receive 20 mg apremilast tablets twice daily in the 24-week placebo-controlled phase and continued to receive 20 mg apremilast tablets twice daily (BID) for up to Week 52 in the active treatment.

At week 52, participants were given the option to remain on active treatment for 1 additional year (extension phase) as assigned during the active treatment phase.

Drug: Apremilast 20 mg
Other Names:
  • CC-10004
  • Otezla
Placebo Comparator: Placebo
Participants initially randomized to receive placebo tablets twice daily in the 24-week placebo-controlled phase. Participants who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to 20 mg apremilast twice daily (early escape). At Week 24, participants remaining on placebo were transitioned onto to 20 mg apremilast tablets twice daily for up to 52 weeks. At week 52, they were given the option to remain on active treatment for 1 additional year (extension phase) as assigned during the active treatment phase.
Drug: Apremilast 20 mg
Other Names:
  • CC-10004
  • Otezla
Drug: Placebo

  Eligibility

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

Inclusion Criteria:

  • Must have a documented diagnosis of Rheumatoid Arthritis (1987 American College of Rheumatology Criteria) with onset of signs/symptoms of disease ≥ 4 months of duration from randomization.
  • Must be receiving treatment on an outpatient basis.
  • Must have active disease despite current methotrexate treatment as defined below:

    • ≥ 6 swollen joints (66 swollen joint count) AND
    • ≥ 6 tender joints (68 tender joint count)

      -. Must meet at least one of the four lab requirements below:

    • High Sensitivity C-Reactive Protein (hsCRP) ≥ 10 mg/L
    • Erythrocyte Sedimentation Rate (ESR) > 28 mm after the first 1 hour
    • Positive for Rheumatoid Factor (RF)
    • Positive for Anti-cyclic Citrullinated Peptide (anti-CCP) antibodies
  • For participants participating in the Magnetic Resonance Imaging (MRI) assessment:

    • Must have Rheumatoid Arthritis joint involvement, as assessed by swollen joint counts in: 1) at least two Metacarpophalangeal (MCP) swollen joints on the same hand, or 2) at least one swollen Metacarpophalangeal (MCP) joint and swollen wrist on the same hand.

  • Must have been treated with methotrexate for at least 4 months prior to randomization, and must be on stable dose. Participants will be required to maintain their stable dose through Week 52 of the study. Oral folate (folic acid) supplementation is required with a minimum dose of 5 mg/week, or instead leucovorin may be used up to 10 mg/week orally.

    • Non-steroidal anti-inflammatory drugs (NSAIDs) and pain medications are allowed, however, must be on stable regimen for at least 7 days prior to randomization and through Week 52 of the study.

  • Oral corticosteroids (if taken) are allowed, however, must be on stable dose of prednisone ≤ 10 mg/day or equivalent for at least 28 days prior to randomization and through Week 52 of the study.
  • Must meet the following laboratory criteria at screening:

    • White blood cell count ≥ 3000/mm^3 (≥ 3.0 x 10^9/L) and < 14,000/mm^3 (< 14 x 10^9/L)
    • Platelet count (≥ 100,000/μL ((≥ 100 x 10^9/L)
    • Serum creatinine ≤ 1.5 mg/dL (≤ 132.6 μmol/L)
    • Aspartate aminotransferase or serum glutamic oxaloacetic transaminase (AST/SGOT) and alanine aminotransferase or serum glutamic-pyruvic transaminase (ALT/ SGPT) ≤ 2 x upper limit of normal (ULN). If initial test shows Aspartate aminotransferase (AST) or alanine aminotransferase (SLT) or 2 times the upper limit of normal (ULN), one repeat test is allowed during the screening period.
    • Total bilirubin ≤ 2 mg/dL (≤ 34 μmol/L). If initial test result is > 2 mg/dL, one repeat test is allowed during the screening period.
    • Hemoglobin ≥ 9 g/dL (≥ 5.6 mmol/L)
    • Hemoglobin A1c ≤ 9.0%
    • Negative for hepatitis B surface antigen
    • Negative for hepatitis C antibody
  • Males who engage in activity in which conception is possible must use protocol described barrier contraception while on Investigational Product and for at least 28 days after the last dose of Investigational Product.
  • Females of childbearing potential (FCBP) must have a negative pregnancy test at Screening and Baseline. FCBP who engage in activity in which conception is possible must use protocol described contraception while on Investigational Product and for at least 28 days after taking the last dose or Investigational Product.

Exclusion Criteria:

  • Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following randomization.
  • Rheumatic autoimmune disease other than Rheumatoid Arthritis, including systemic lupus erythematosus, mixed connective tissue disease, scleroderma, polymyositis or significant systemic involvement secondary to Rheumatoid Arthritis (eg, vasculitis, pulmonary fibrosis or Felty syndrome). Sjögren syndrome secondary to Rheumatoid Arthritis is allowable.
  • Functional Class IV as defined by the American College of Rheumatology (ACR) Classification of Functional Status in Rheumatoid Arthritis.
  • Prior history of, or current, inflammatory joint disease other than Rheumatoid Arthritis (eg, gout, reactive arthritis, psoriatic arthritis, ankylosing spondylitis, Lyme disease).
  • Receiving treatment with Disease-modifying antirheumatic drugs (DMARDs) (other than methotrexate), including biologic Disease-modifying antirheumatic drugs (DMARDs)Previous use is only allowed after adequate washout prior to randomization.
  • Inadequate response to treatment with an anti-tumor necrosis factor (anti-TNF) agent. Patients who terminated previous anti-tumor necrosis factor (anti-TNF) treatment due to cost or safety reason, such as discomfort with the subcutaneous injections, may participate in this study after adequate washout.
  • Treatment with any investigational agent within four weeks (or five half-lives of the investigational drug, whichever is longer) of screening.
  • Previous treatment with any cell depleting therapies, including investigational agents.
  • Treatment with intravenous gamma globulin, plasmapheresis or Prosorba® column within 6 months of baseline.
  • Intra-articular or parenteral corticosteroids are not allowed within 6 weeks prior to randomization.
  • Any previous treatment with alkylating agents such as cyclophosphamide or chlorambucil, or with total lymphoid irradiation.
  • Pregnant women or nursing (breast feeding) mothers.
  • Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary (including severe or very severe chronic obstructive pulmonary disease), renal, hepatic, endocrine (including uncontrolled diabetes mellitus as defined by Hemoglobin A1c > 9.0%) or gastrointestinal (GI) disease.
  • Uncontrolled disease states, such as asthma, psoriasis or inflammatory bowel disease, where flares are commonly treated with oral or parenteral corticosteroids.
  • Known active current or history of recurrent bacterial, viral, fungal, mycobacterial or other infections (including but not limited to tuberculosis and atypical mycobacterial disease, Hepatitis B and C, and herpes zoster, but excluding onychomycosis) or any major episode of infection requiring hospitalization or treatment with IV or oral antibiotics within 4 weeks of screening.
  • History of positive Human Immunodeficiency Virus (HIV), or congenital or acquired immunodeficiency (eg, Common Variable Immunodeficiency Disease).
  • History of malignancy, including solid tumors and hematologic malignancies (except basal cell carcinoma of the skin that has been excised and cured).
  • History of alcohol, drug or chemical abuse within the 6 months prior to screening.
  • Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
  • Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
  • Any condition that in the investigator's opinion would interfere significantly with the efficacy evaluations, including the pain and joint assessments (eg, fibromyalgia).

For Magnetic Resonance Imaging (MRI) Only:

  • Receiving medication(s) or will require medication(s) during the study that impact on vascular flow (eg, nitrates, calcium channel blockers, ergot containing drugs) on the day of the Magnetic Resonance Imaging (MRI test and in the investigator's judgement the subject cannot hold back from taking these medications on the day of the Magnetic Resonance Imaging (MRI) prior to the Magnetic Resonance Imaging (MRI) test. The subject can continue taking the medication(s) at any time after the Magnetic Resonance Imaging (MRI) test is completed, as clinically indicated and scheduled. Exclusions of antihypertensive and migraine medications can be determined after discussion with the Sponsor.
  • Unable to undergo an Magnetic Resonance Imaging (MRI) examination, including but not limited to the presence of a pacemaker, defibrillator, or other implanted device such as anterior interbody cages, aneurysm clip, pedicle screws, or any other metal contained in the body (eg, such as tattoos that contain metallic pigment, or metal in the eyes from metal grinding [eg, a metal worker, etc]), or severe claustrophobia, or any other contraindication to an Magnetic Resonance Imaging (MRI) as per local imaging center guidelines.
  • Allergic or adverse reactions to gadolinium
  • Estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73m2 (based on the Modification of Diet in Renal Disease [MDRD] formula).
  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: NCT01285310

  Show 50 Study Locations
Sponsors and Collaborators
Celgene Corporation
Investigators
Study Director: Randall Stevens, MD Celgene Corporation
  More Information

No publications provided

Responsible Party: Celgene Corporation
ClinicalTrials.gov Identifier: NCT01285310     History of Changes
Other Study ID Numbers: CC-10004-RA-002, 2010-019926-15
Study First Received: November 19, 2010
Results First Received: April 22, 2014
Last Updated: August 13, 2014
Health Authority: United States: Food and Drug Administration
Czech Republic: State Institute for Drug Control
Germany: Federal Institute for Drugs and Medical Devices
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Spain: Agencia Española de Medicamentos y Productos Sanitarios

Keywords provided by Celgene Corporation:
Rheumatoid, Arthritis

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Apremilast
Thalidomide
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
Antirheumatic Agents
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Central Nervous System Agents
Immunosuppressive Agents
Immunologic Factors
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Angiogenesis Inhibitors

ClinicalTrials.gov processed this record on October 19, 2014