PALACE 3: Efficacy and Safety Study of Apremilast to Treat Active Psoriatic Arthritis

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT01212770
First received: September 29, 2010
Last updated: April 22, 2014
Last verified: April 2014
  Purpose

The purpose of this study is to determine whether apremilast is safe and effective in the treatment of patients with psoriatic arthritis, specifically in improving signs and symptoms of psoriatic arthritis (tender and swollen joints, pain, physical function) in treated patients.


Condition Intervention Phase
Psoriatic Arthritis
Drug: Apremilast
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Efficacy and Safety Study of Two Doses Of Apremilast (CC-10004) In Subjects With Active Psoriatic Arthritis And A Qualifying Psoriasis Lesion

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% (ACR20) 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% (ACR20) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met:

    • ≥ 20% improvement in 78 tender joint count;
    • ≥ 20% improvement in 76 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 100 mm VAS);
      • Physician's global assessment of disease activity (measured on a 100 mm VAS);
      • Patient'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 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 With an 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% (ACR20) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met:

    • ≥ 20% improvement in 78 tender joint count;
    • ≥ 20% improvement in 76 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 100 mm VAS);
      • Physician's global assessment of disease activity (measured on a 100 mm VAS);
      • Patient'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 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 36-item Short Form Health Survey (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). 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.

  • Percentage of Participants With a Modified Psoriatic Arthritis Response Criteria (PsARC) Response at Week 16 [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]

    Modified PsARC response is defined as improvement in at least 2 of the 4 measures, at least one of which must be tender joint count or swollen joint count, and no worsening in any of the 4 measures:

    • 78 tender joint count,
    • 76 swollen joint count,
    • Patient 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 global assessment of disease activity, measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest.

    Improvement or worsening in joint counts is defined as decrease or increase, respectively, from baseline by ≥ 30%, and improvement or worsening in global assessments is defined as decrease or increase, respectively, from baseline by ≥ 20 mm VAS.


  • Percentage of Participants Achieving a ≥ 75% Improvement in Psoriasis Area and Severity Index Score (PASI75) at Week 16 [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]

    The percentage of participants with Baseline psoriasis body surface area (BSA) involvement ≥ 3% who achieved 75% or greater improvement from Baseline in Psoriasis Area and Severity Index (PASI) score after 16 weeks of treatment.

    The Psoriasis Area and Severity Index (PASI) score is a combination of the intensity of psoriasis, assessed by erythema (reddening), induration (plaque thickness) and desquamation (scaling) scored on a scale from 0 (none) to 4 (very severe), together with the percentage of the area affected, rated on a scale from 0 (no involvement) to 6 (90% to 100% involvement). PASI scoring is performed at four body areas, the head, arms, trunk, and legs. The total PASI score ranges from 0 to 72. The higher the total score, the more severe the disease.


  • Change From Baseline in Patient's Assessment of Pain at Week 16 [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]
    The participant was asked 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.

  • Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at Week 16 [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]

    The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone):

    1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right.

    The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses.


  • Change From Baseline in Dactylitis Severity Score at Week 16 [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]
    Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present.

  • Change From Baseline in 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),
    • Patient's Global Assessment of Disease Activity measured on a 10 cm visual analog scale (VAS), where 0 cm = lowest disease activity and 10 cm = highest;
    • Physician's Global Assessment of Disease Activity -measured on a 10 cm VAS, where 0 cm = lowest disease activity and 10 cm = 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 (DAS28) 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
    • 28 swollen joint count, which do not include the distal interphalangeal (DIP) joints, the hip joint, or the joints below the knee;
    • C-reactive protein (CRP)
    • Patient's global assessment of disease activity.

    DAS28(CRP) scores range from 0 to approximately 10, with the upper bound dependent on the highest possible level of CRP. 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.


  • 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 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.

  • Change From Baseline in 36-item Short Form Health Survey (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.

  • Percentage of Participants With a Modified Psoriatic Arthritis Response Criteria (PsARC) Response at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]

    Modified PsARC response is defined as improvement in at least 2 of the 4 measures, at least one of which must be tender joint count or swollen joint count, and no worsening in any of the 4 measures:

    • 78 tender joint count,
    • 76 swollen joint count,
    • Patient 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 global assessment of disease activity, measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest.

    Improvement or worsening in joint counts is defined as decrease or increase, respectively, from baseline by ≥ 30%, and improvement or worsening in global assessments is defined as decrease or increase, respectively, from baseline by ≥ 20 mm VAS.


  • Percentage of Participants Achieving a ≥ 75% Improvement in Psoriasis Area and Severity Index Score (PASI75) at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]

    The percentage of participants with Baseline psoriasis body surface area (BSA) involvement ≥ 3% who achieved 75% or greater improvement from Baseline in Psoriasis Area and Severity Index (PASI) score after 24 weeks of treatment.

    The Psoriasis Area and Severity Index (PASI) score is a combination of the intensity of psoriasis, assessed by erythema (reddening), induration (plaque thickness) and desquamation (scaling) scored on a scale from 0 (none) to 4 (very severe), together with the percentage of the area affected, rated on a scale from 0 (no involvement) to 6 (90% to 100% involvement). PASI scoring is performed at four body areas, the head, arms, trunk, and legs. The total PASI score ranges from 0 to 72. The higher the total score, the more severe the disease.


  • Change From Baseline in Patient's Assessment of Pain at Week 24 [ Time Frame: Baseline and week 24 ] [ Designated as safety issue: No ]
    The participant was asked 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.

  • Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at Week 24 [ Time Frame: Baseline and week 24 ] [ Designated as safety issue: No ]

    The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone):

    1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right.

    The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses.


  • Change From Baseline in Dactylitis Severity Score at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet will be rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present.

  • Change From Baseline in 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),
    • Patient's Global Assessment of Disease Activity measured on a 10 cm visual analog scale (VAS), where 0 cm = lowest disease activity and 10 cm = highest;
    • Physician's Global Assessment of Disease Activity -measured on a 10 cm VAS, where 0 cm = lowest disease activity and 10 cm = 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 (DAS28) 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)
    • Patient's global assessment of disease activity.

    DAS28(CRP) scores range from 0 to approximately 10, with the upper bound dependent on the highest possible level of CRP. 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.


  • 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 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 With MASES Improvement ≥ 20% at Week 16 [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]

    Percentage of participants with pre-existing enthesopathy whose MASES improved by ≥ 20% from Baseline after 16 weeks of treatment. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone):

    1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right.

    The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses.


  • Percentage of Participants With Dactylitis Improvement ≥ 1 Point at Week 16 [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]

    Percentage of participants with pre-existing dactylitis whose dactylitis severity score improved by ≥ 1 after 16 weeks of treatment.

    Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present.


  • Percentage of Participants With Good or Moderate European League Against Rheumatism (EULAR) Response at Week 16 [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]

    A EULAR response reflects an improvement in disease activity and an attainment of a lower degree of disease activity based on the DAS-28 score.

    A Good Response is defined as an improvement (decrease) in the DAS28 of more than 1.2 compared with Baseline and attainment of a DAS28 score less than or equal to 3.2.

    A Moderate Response is defined as either:

    • an improvement (decrease) in the DAS28 of greater than 0.6 and less than or equal to 1.2 and attainment of a DAS28 score of less than or equal to 5.1 or,
    • an improvement (decrease) in the DAS28 of more than 1.2 and attainment of a DAS28 score of greater than 3.2.

  • Percentage of Participants With MASES Improvement ≥ 20% at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]

    Percentage of participants with pre-existing enthesopathy whose MASES improved by ≥ 20% from Baseline after 24 weeks of treatment. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone):

    1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right.

    The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses.


  • Percentage of Participants With Dactylitis Improvement ≥ 1 Point at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]

    Percentage of participants with pre-existing dactylitis whose dactylitis severity score improved by ≥ 1 after 24 weeks of treatment.

    Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present.


  • Percentage of Participants With Good or Moderate EULAR Response at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]

    EULAR response reflects an improvement in disease activity and an attainment of a lower degree of disease activity based on the DAS-28 score.

    A Good Response is defined as an improvement (decrease) in the DAS28 of more than 1.2 compared with Baseline and attainment of a DAS28 score less than or equal to 3.2.

    A Moderate Response is defined as either:

    • an improvement (decrease) in the DAS28 of greater than 0.6 and less than or equal to 1.2 and attainment of a DAS28 score of less than or equal to 5.1 or,
    • an improvement (decrease) in the DAS28 of more than 1.2 and attainment of a DAS28 score of greater than 3.2.

  • Percentage of Participants With a 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% (ACR50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met:

    • ≥ 50% improvement in 78 tender joint count;
    • ≥ 50% improvement in 76 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 100 mm VAS);
      • Physician's global assessment of disease activity (measured on a 100 mm VAS);
      • Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI));
      • C-Reactive Protein.

  • Percentage of Participants With an 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% (ACR70) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met:

    • ≥ 70% improvement in 78 tender joint count;
    • ≥ 70% improvement in 76 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 100 mm VAS);
      • Physician's global assessment of disease activity (measured on a 100 mm VAS);
      • Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI));
      • C-Reactive Protein.

  • Percentage of Participants With an 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% (ACR50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met:

    • ≥ 50% improvement in 78 tender joint count;
    • ≥ 50% improvement in 76 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 100 mm VAS);
      • Physician's global assessment of disease activity (measured on a 100 mm VAS);
      • Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI));
      • C-Reactive Protein.

  • Percentage of Participants With a 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% (ACR70) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met:

    • ≥ 70% improvement in 78 tender joint count;
    • ≥ 70% improvement in 76 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 100 mm VAS);
      • Physician's global assessment of disease activity (measured on a 100 mm VAS);
      • Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI));
      • C-Reactive Protein.

  • Percentage of Participants Achieving a MASES Score of Zero at Week 16 [ Time Frame: Week 16 ] [ Designated as safety issue: No ]

    Percentage of participants with pre-existing enthesopathy whose MASES improves to 0 after 16 weeks of treatment. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone):

    1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right.

    The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses.


  • Percentage of Participants Achieving a Dactylitis Score of Zero at Week 16 [ Time Frame: Week 16 ] [ Designated as safety issue: No ]

    Percentage of participants with pre-existing dactylitis whose dactylitis severity score improves to zero after 16 weeks of treatment.

    Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present.


  • Percentage of Participants Achieving a MASES Score of Zero at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]

    Percentage of participants with pre-existing enthesopathy whose MASES improves to 0 after 24 weeks of treatment. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone):

    1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right.

    The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses.


  • Percentage of Participants Achieving a Dactylitis Score of Zero at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]

    Percentage of participants with pre-existing dactylitis whose dactylitis severity score improves to zero after 24 weeks of treatment.

    Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present.


  • Percentage of Participants With an 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% (ACR20) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met:

    • ≥ 20% improvement in 78 tender joint count;
    • ≥ 20% improvement in 76 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 100 mm VAS);
      • Physician's global assessment of disease activity (measured on a 100 mm VAS);
      • Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI));
      • C-Reactive Protein.

    Two-sided 95% confidence interval is based on the Clopper-Pearson method.


  • 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 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 SF-36 Physical Functioning Scale Score 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.

  • Percentage of Participants With a Modified PsARC Response at Week 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]

    Modified PsARC response is defined as improvement in at least 2 of the 4 measures, at least one of which must be tender joint count or swollen joint count, and no worsening in any of the 4 measures:

    • 78 tender joint count,
    • 76 swollen joint count,
    • Patient 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 global assessment of disease activity, measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest.

    Improvement or worsening in joint counts is defined as decrease or increase, respectively, from baseline by ≥ 30%, and improvement or worsening in global assessments is defined as decrease or increase, respectively, from baseline by ≥ 20 mm VAS.

    Two-sided 95% confidence interval is based on the Clopper-Pearson method.


  • Percentage of Participants Achieving a ≥ 75% Improvement in Psoriasis Area and Severity Index Score (PASI75) at Week 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]

    The percentage of participants with Baseline psoriasis body surface area (BSA) involvement ≥ 3% who achieved 75% or greater improvement from Baseline in Psoriasis Area and Severity Index (PASI) score after 52 weeks.

    The Psoriasis Area and Severity Index (PASI) score is a combination of the intensity of psoriasis, assessed by erythema (reddening), induration (plaque thickness) and desquamation (scaling) scored on a scale from 0 (none) to 4 (very severe), together with the percentage of the area affected, rated on a scale from 0 (no involvement) to 6 (90% to 100% involvement). PASI scoring is performed at four body areas, the head, arms, trunk, and legs. The total PASI score ranges from 0 to 72. The higher the total score, the more severe the disease.

    Two-sided 95% confidence interval is based on the Clopper-Pearson method.


  • Change From Baseline in the Patient Assessment of Pain at Week 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]
    The participant was asked 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.

  • Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at Week 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]

    The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone):

    1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right.

    The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses.


  • Change From Baseline in the Dactylitis Severity Score at Week 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]
    Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet will be rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present.

  • Change From Baseline in the CDAI Score 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),
    • Patient's Global Assessment of Disease Activity measured on a 10 cm visual analog scale (VAS), where 0 cm = lowest disease activity and 10 cm = highest;
    • Physician's Global Assessment of Disease Activity -measured on a 10 cm VAS, where 0 cm = lowest disease activity and 10 cm = 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 DAS28 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
    • 28 swollen joint count, which do not include the DIP joints, the hip joint, or the joints below the knee;
    • C-reactive protein (CRP)
    • Patient's global assessment of disease activity.

    DAS28(CRP) scores range from 0 to approximately 10, with the upper bound dependent on the highest possible level of CRP. 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.


  • 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 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 With MASES Improvement ≥ 20% at Week 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]

    Percentage of participants with pre-existing enthesopathy whose MASES improved by ≥ 20% from Baseline after 52 weeks. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone):

    1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right.

    The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses.

    Two-sided 95% confidence interval is based on the Clopper-Pearson method.


  • Percentage of Participants With Dactylitis Improvement ≥ 1 Point at Week 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]

    Percentage of participants with pre-existing dactylitis whose dactylitis severity score improved by ≥ 1 after 52 weeks.

    Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severiy score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present.

    Two-sided 95% confidence interval is based on the Clopper-Pearson method.


  • Percentage of Participants Achieving Good or Moderate EULAR Response at Week 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]

    A EULAR response reflects an improvement in disease activity and an attainment of a lower degree of disease activity based on the DAS-28 score.

    A Good Response is defined as an improvement (decrease) in the DAS28 of more than 1.2 compared with Baseline and attainment of a DAS28 score less than or equal to 3.2.

    A Moderate Response is defined as either:

    • an improvement (decrease) in the DAS28 of greater than 0.6 and less than or equal to 1.2 and attainment of a DAS28 score of less than or equal to 5.1 or,
    • an improvement (decrease) in the DAS28 of more than 1.2 and attainment of a DAS28 score of greater than 3.2.

    Two-sided 95% confidence interval is based on the Clopper-Pearson method.


  • Percentage of Participants With an 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% (ACR50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met:

    • ≥ 50% improvement in 78 tender joint count;
    • ≥ 50% improvement in 76 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 100 mm VAS);
      • Physician's global assessment of disease activity (measured on a 100 mm VAS);
      • Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI));
      • C-Reactive Protein.

    Two-sided 95% confidence interval is based on the Clopper-Pearson method.


  • Percentage of Participants With an 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% (ACR70) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met:

    • ≥ 70% improvement in 78 tender joint count;
    • ≥ 70% improvement in 76 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 100 mm VAS);
      • Physician's global assessment of disease activity (measured on a 100 mm VAS);
      • Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI));
      • C-Reactive Protein.

    Two-sided 95% confidence interval is based on the Clopper-Pearson method.


  • Percentage of Participants Achieving a MASES Score of Zero at Week 52 [ Time Frame: Week 52 ] [ Designated as safety issue: No ]

    Percentage of participants with pre-existing enthesopathy whose MASES improves to 0 after 24 weeks. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone):

    1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right.

    The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses.

    Two-sided 95% confidence interval is based on the Clopper-Pearson method.


  • Percentage of Participants Achieving a Dactylitis Score of Zero at Week 52 [ Time Frame: Week 52 ] [ Designated as safety issue: No ]

    Percentage of participants with pre-existing dactylitis whose dactylitis severity score improves to zero after 52 weeks.

    Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present.

    Two-sided 95% confidence interval is based on the Clopper-Pearson method.


  • Number of Participants With Adverse Events [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]

Enrollment: 505
Study Start Date: September 2010
Estimated Study Completion Date: December 2016
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 either 20 mg or 30 mg apremilast twice daily (early escape). At Week 24, participants remaining on placebo were re-randomized to 20 mg or 30 mg apremilast for up to 4.5 years.
Drug: Placebo
Placebo tablets
Experimental: Apremilast 20 mg
Participants initially randomized to receive 20 mg apremilast tablets twice daily during the 24-week placebo-controlled phase continued to receive 20 mg apremilast tablets twice daily for up to 4.5 years in the active treatment / long-term safety phase.
Drug: Apremilast
Apremilast tablets
Other Names:
  • CC-10004
  • Otezla
Placebo Comparator: Apremilast 30 mg
Participants initially randomized to receive 30 mg apremilast tablets twice daily during the 24-week placebo-controlled phase continued to receive 30 mg apremilast tablets twice daily for up to 4.5 years in the active treatment / long-term safety phase.
Drug: Apremilast
Apremilast tablets
Other Names:
  • CC-10004
  • Otezla

Detailed Description:

Psoriatic arthritis (PsA) is an inflammatory arthritis that occurs in 6-39% of psoriasis patients. The immunopathogenesis of PsA, which mirrors but is not identical to that seen in psoriatic plaques, reflects a complex interaction among resident dendritic, fibroblastic and endothelial cells, and inflammatory cells attracted to the synovium by cytokines and chemokines. Apremilast (CC-10004) is a novel oral agent that modulates multiple inflammatory pathways through targeted phosphodiesterase type 4 (PDE4) enzyme inhibition. Therefore, apremilast has the potential to be effective in the treatment of PsA.

  Eligibility

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

Inclusion Criteria:

  • Males or females, aged ≥ 18 years at time of consent.
  • Have a diagnosis of Psoriatic Arthritis (PsA, by any criteria) of ≥ 6 months duration.
  • Meet the Classification Criteria for Psoriatic Arthritis (CASPAR) at time of screening.
  • Must have been inadequately treated by disease-modifying antirheumatic drugs (DMARDs)
  • May not have axial involvement alone
  • Concurrent treatment allowed with methotrexate, leflunomide, or sulfasalazine
  • Have ≥ 3 swollen AND ≥ 3 tender joints.
  • Males & females must use contraception
  • Stable dose of nonsteroidal anti-inflammatory drugs (NSAIDs), narcotics and low dose oral corticosteroids allowed.
  • Have at least one ≥ 2 cm psoriasis lesion

Exclusion Criteria:

  • Pregnant or breast feeding.
  • History of allergy to any component of the investigational product Hepatitis B surface antigen and/or Hepatitis C antibody positive at screening.
  • Therapeutic failure on > 3 agents for PsA or > 1 biologic tumor necrosis factor (TNF) blocker
  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: NCT01212770

  Show 67 Study Locations
Sponsors and Collaborators
Celgene Corporation
Investigators
Study Director: Douglas Hough, MD Celgene Corporation
  More Information

No publications provided

Responsible Party: Celgene Corporation
ClinicalTrials.gov Identifier: NCT01212770     History of Changes
Other Study ID Numbers: CC-10004-PSA-004
Study First Received: September 29, 2010
Results First Received: April 22, 2014
Last Updated: April 22, 2014
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
United States: Food and Drug Administration
Canada: Health Canada
Finland: Finnish Medicines Agency
Germany: Federal Institute for Drugs and Medical Devices
Italy: The Italian Medicines Agency
Lithuania: State Medicine Control Agency - Ministry of Health
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Romania: National Medicines Agency
Russia: Pharmacological Committee, Ministry of Health
Slovakia: State Institute for Drug Control
South Korea: Korea Food and Drug Administration (KFDA)
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Switzerland: Swissmedic
United Kingdom: Medicines and Healthcare Products Regulatory Agency
France: Agence Nationale de Sécurité du Médicament et des produits de santé

Keywords provided by Celgene Corporation:
Psoriatic Arthritis
Psoriasis
Arthritis
inflammation
skin condition
inflammatory cells
apremilast
CC-10004
phosphodiesterase type 4

Additional relevant MeSH terms:
Arthritis
Arthritis, Psoriatic
Joint Diseases
Musculoskeletal Diseases
Spondylarthropathies
Spondylarthritis
Spondylitis
Spinal Diseases
Bone Diseases
Psoriasis
Skin Diseases, Papulosquamous
Skin Diseases
Thalidomide
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents

ClinicalTrials.gov processed this record on July 22, 2014