| April 2, 2007
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| April 4, 2007
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| August 27, 2018
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| October 23, 2019
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| June 19, 2020
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| March 5, 2007
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| May 9, 2009 (Final data collection date for primary outcome measure)
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| Percentage of Participants With a Modified American College of Rheumatology 20% (ACR 20) Response at Week 12 [ Time Frame: Baseline and Week 12 ] A modified American College of Rheumatology 20% (ACR 20) response was defined as a participant who met the following 3 criteria for improvement from Baseline: • ≥ 20% improvement in 78 tender joint count (includes 10 additional joints often involved in psoriatic arthritis: the first carpometacarpal [CMC] and the distal interphalangeal [DIP] joints of the fingers); • ≥ 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. Participants with no post-baseline ACR scores were considered non-responders.
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| Proportion of subjects in each treatment group who achieve ACR criteria for 20% improvement at Day 85/Early termination visit compared with baseline
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- Number of Participants With Adverse Events During the Treatment Phase [ Time Frame: 12 weeks ]
The severity of each adverse event (AE) was graded based upon the participant's symptoms according to National Cancer Institute (NCI) Common Toxicity Criteria (CTCAE, Version 3.0), on a scale from 1 (Mild AE) to 5 (Death due to AE). Severe AEs are defined as NCI CTCAE grade 3 or higher. AEs related to study drug are those determined by the investigator as suspected to be related to study drug where a temporal relationship of the adverse event to study drug administration made a causal relationship possible, and other medications, therapeutic interventions, or underlying conditions did not provide a sufficient explanation for the observed event. A serious adverse event (SAE) is any AE which: - Resulted in death - Was life-threatening - Required inpatient hospitalization or prolongation of existing hospitalization - Resulted in persistent or significant disability/incapacity - Was a congenital anomaly/birth defect - Constituted an important medical event.
- Percentage of Participants With a Psoriatic Arthritis Response Criteria (PsARC) Response at Week 12 [ Time Frame: Baseline and Week 12 ]
A PsARC response is defined as improvement from Baseline in at least 2 of the following 4 measures, at least 1 of which must be tender joint count or swollen joint count, and no worsening in any of the 4 measures, according to the following: • At least 30% improvement in the 78 tender joint count, • At least 30% improvement in the 76 swollen joint count, • At least 20% improvement in the 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; • At least 20% improvement in the physician global assessment of disease activity, measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest. Participants with no post-baseline PsARC scores were considered non-responders.
- Percentage of Participants With a Modified ACR 50 Response at Week 12 [ Time Frame: Baseline and Week 12 ]
A modified American College of Rheumatology 50% (ACR 50) response was defined as a participant who met the following 3 criteria for improvement from Baseline: • ≥ 50% improvement in 78 tender joint count (includes 10 additional joints often involved in psoriatic arthritis: the first carpometacarpal [CMC] and the distal interphalangeal [DIP] joints of the fingers); • ≥ 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. Participants with no post-baseline ACR scores were considered non-responders.
- Percentage of Participants With a Modified ACR 70 Response at Week 12 [ Time Frame: Baseline and Week 12 ]
A modified American College of Rheumatology 70% (ACR 70) response was defined as a participant who met the following 3 criteria for improvement from Baseline: • ≥ 70% improvement in 78 tender joint count (includes 10 additional joints often involved in psoriatic arthritis: the first carpometacarpal [CMC] and the distal interphalangeal [DIP] joints of the fingers); • ≥ 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. Participants with no post-baseline ACR scores were considered non-responders.
- Percentage of Participants With Good or Moderate European League Against Rheumatism (EULAR) Response Based on Disease Activity Score (DAS28)-CRP(4) at Week 12 [ Time Frame: Baseline and Week 12 ]
The DAS28 measures the severity of disease at a specific time. DAS28-CRP(4) is derived from the following 4 variables: • 28 tender joint count, (TJC; does not include the DIP joints, the hip joint, or the joints below the knee) • 28 swollen joint count (SJC) • C-reactive protein (CRP) • Patient's global assessment of disease activity (GH) according to the formula: DAS28-CRP(4) = 0.56*√(TJC28) + 0.28*(SJC28) + 0.36*ln(CRP+1) + 0.014*GH + 0.96. DAS28 scores range from 0 to 9.4, where higher scores indicate more disease activity. A EULAR response reflects an improvement in disease activity based on the DAS-28 score. A Good Response is defined as an improvement (decrease) in the DAS28 > 1.2 from Baseline and a DAS28 score ≤ 3.2. A Moderate Response is defined as either: • an improvement (decrease) in the DAS28 > 0.6 and ≤ 1.2 and a DAS28 score ≤ to 5.1 or, • an improvement (decrease) in the DAS28 > 1.2 and a DAS28 score > 3.2
- Percentage of Participants With Good or Moderate EULAR Response Based on DAS28-CRP(3) at Week 12 [ Time Frame: Baseline and Week 12 ]
The DAS28 measures the severity of disease at a specific time. DAS28-CRP(3) is derived from the following 3 variables: • 28 tender joint count, (does not include the DIP joints, the hip joint, or the joints below the knee) • 28 swollen joint count • C-reactive protein (CRP) according to the formula: DAS28-CRP(3) = [0.56*√(TJC28) + 0.28*√(SJC28) + 0.36*ln(CRP+1)] * 1.10 + 1.15. DAS28 scores range from 0 to 9.4, where higher scores indicate more disease activity. A EULAR response reflects an improvement in disease activity based on the DAS-28 score. A Good Response is defined as an improvement (decrease) in the DAS28 > 1.2 from Baseline and attainment of a DAS28 score ≤ 3.2. A Moderate Response is defined as either: • an improvement (decrease) in the DAS28 > 0.6 and ≤ 1.2 and a DAS28 score ≤ to 5.1 or, • an improvement (decrease) in the DAS28 > 1.2 and a DAS28 score > 3.2
- Percentage of Participants With DAS28-CRP(4) Score of Mild Disease Activity or In Remission at Week 12 [ Time Frame: Week 12 ]
The DAS28-CRP(4) measures the severity of disease derived from the following 4 variables: • 28 tender joint count, (does not include the DIP joints, the hip joint, or the joints below the knee) • 28 swollen joint count • C-reactive protein (CRP) • Patient's global assessment of disease activity. DAS28-CRP(4) scores range from 0 to 9.4, where higher scores indicate more disease activity. Mild disease severity is defined as a DAS28-CRP(4) score of ≤ 3.2. In remission is defined as a DAS28-CRP(4) score of ≤ 2.6.
- Percentage of Participants With DAS28-CRP(3) Score of Mild Disease Activity or In Remission at Week 12 [ Time Frame: Week 12 ]
The DAS28-CRP(3) measures the severity of disease derived from the following 3 variables: • 28 tender joint count (does not include the DIP joints, the hip joint, or the joints below the knee) • 28 swollen joint count • C-reactive protein (CRP) DAS28-CRP(3) scores range from 0 to 9.4, where higher scores indicate more disease activity. Mild disease severity is defined as a DAS28-CRP(3) score of ≤ 3.2. In remission is defined as a DAS28-CRP(3) score of ≤ 2.6.
- Number of Participants Who Withdrew Prematurely Due to Lack of Efficacy [ Time Frame: Baseline to Week 12 ]
The number of participants who withdrew prematurely from the treatment phase due to lack of efficacy, including flare of psoriasis, flare of psoriatic arthritis or worsening or not responding to study treatment.
- Number of Participants With Adverse Events Leading to a Dose Reduction [ Time Frame: Baseline to Week 12 ]
The number of participants who were dose reduced during the treatment phase due to adverse events.
- Maximal ACR Response During the Treatment Phase [ Time Frame: ACR was measured at Baseline and Weeks 2, 4, 6, 8, 10, and 12 ]
The ACR-N index score was calculated for each participant at each time point in the study according to the following definition: ACR-N = the lowest of the following 3 values: - percent improvement from Baseline in the 76 swollen joint count, - percent improvement from Baseline in the 78 tender joint count - median percent improvement from Baseline in the following 5 measures ◦ 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. The maximal ACR-N for each participant during the 12-week treatment period was calculated, and represents the maximal ACR response achieved.
- Time to ACR 20 Response During the Treatment Phase [ Time Frame: Baseline to Week 12 ]
The Kaplan-Meier estimates of time to ACR 20 response was calculated for participants who had an ACR 20 response at any time during the treatment phase.
- Time to ACR 50 Response During the Treatment Phase [ Time Frame: Baseline to Week 12 ]
The Kaplan-Meier estimates of time to ACR 50 response was calculated for participants who had an ACR 50 response at any time during the treatment phase.
- Time to ACR 70 Response During the Treatment Phase [ Time Frame: Baseline to Week 12 ]
The Kaplan-Meier estimates of time to ACR 70 response was calculated for participants who had an ACR 70 response at any time during the treatment phase.
- Change From Baseline in Dactylitis Severity Score at Week 12 [ Time Frame: Baseline and Week 12 ]
Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated on a scale from 0 (no dactylitis) to 3 (severe dactylitis). The dactylitis severity score is the sum of the individual scores for each digit and ranges from 0 to 60.
- Percentage of Participants With Enthesitis [ Time Frame: Baseline and Week 12 ]
Enthesitis is inflammation of the entheses, the sites where tendons or ligaments insert into the bone. Enthesitis is characterized by swelling, pain, and tenderness around the calcaneous, and occasionally by effusion in the bursa associated with this joint. The enthesitis assessment is an evaluation of inflammation at the insertions of the Achilles tendon into the calcaneous and of the plantar fascia into the calcaneous. Inflammation at 1 or more insertions on either the right or left side constituted a positive assessment.
- Time to Relapse of Psoriatic Arthritis During the Observational Follow-up Phase [ Time Frame: From Week 12 to end of 28-day observational follow-up (1) and from the date of maximal ACR during the 12-week Treatment Phase until the end of the 28-day observational follow-up phase (2). ]
Relapse of psoriatic arthritis was defined as a 50% loss of the maximal ACR improvement during the Observation Phase in participants who received apremilast and achieved at least an ACR 20 at their Final Treatment Phase/Early Termination Visit. The time to relapse during the Observational Phase was calculated from the time of maximum ACR reduction and from the date of the Final Treatment Phase visit. Participants classified as responders who did not relapse were censored at the day of the last follow-up.
- Number of Participants Who Relapsed During the Observational Follow-up Phase [ Time Frame: 28-day observational follow-up period following Week 12 ]
Relapse of psoriatic arthritis was defined as a 50% loss of the maximal ACR improvement during the Observation Phase in participants who received apremilast and achieved at least an ACR 20 at their Final Treatment Phase/Early Termination Visit.
- Change From Baseline in Short Form 36 (SF-36) Summary Physical and Mental Component Scores at Week 12 [ Time Frame: Baseline and Week 12 ]
The Medical Outcome SF 36-Item Health Survey, Version 2 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 summary physical health score included the following subscales: physical functioning, role-physical, bodily pain, and general health. The summary mental health score included other subscales: vitality, social functioning, role-emotional, and mental health. Norm-based scores were used in analyses, calibrated so that 50 is the average score and the standard deviation equals 10, where higher scores are associated with better functioning/quality of life. Each domain is scored by summing the individual items and transforming the scores into a 0 to 100 scale. A higher change from baseline indicates an improvement in better health results or functioning.
- Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 12 [ Time Frame: Baseline and Week 12 ]
The DLQI is a validated, self-administered, 10-item questionnaire that measures the impact of skin disease on participants' quality of life, based on recall over the past week. Domains include symptoms, feelings, daily activities, leisure, work, personal relationships, and treatment. Each question is answered on a scale from 0 (not at all) to 3 (very much). The total score ranges from 0 to 30 where a higher score indicates that a participant's dermatological condition has a greater impact on their daily life.
- Change From Baseline in the Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12 [ Time Frame: Baseline and Week 12 ]
The HAQ-DI is a self-administered instrument consisting of 20 questions in eight categories of functioning which represent a comprehensive set of functional activities - dressing, rising, eating, walking, hygiene, reach, grip, and usual activities. Each item asks over the past week whether a particular task can be performed. For each item, there is a four-level difficulty scale that is scored from 0 to 3, representing normal (no difficulty) (0), some difficulty (1), much difficulty (2), and unable to do (3). The eight category scores are averaged into an overall HAQ-DI score on a scale from zero (no disability) to three (completely disabled).
- Change From Baseline in the Functional Assessment of Chronic Illness Therapy for Fatigue (FACIT-F) at Week 12 [ Time Frame: Baseline and Week 12 ]
The FACIT-Fatigue is a 13 item self-administered questionnaire that assesses both the physical and functional consequences of fatigue based on recall during the past 7 days. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The total score ranges from 0 to 52 with higher scores representing less fatigue.
- Number of Participants With Adverse Events During the Extension Phase [ Time Frame: Weeks 12 to 24 (Extension Phase) ]
The severity of each adverse event (AE) was graded based upon the participant's symptoms according to National Cancer Institute (NCI) Common Toxicity Criteria (CTCAE, Version 3.0), on a scale from 1 (Mild AE) to 5 (Death due to AE). Severe AEs are defined as NCI CTCAE grade 3 or higher. AEs related to study drug are those determined by the investigator as suspected to be related to study drug where a temporal relationship of the adverse event to study drug administration made a causal relationship possible, and other medications, therapeutic interventions, or underlying conditions did not provide a sufficient explanation for the observed event. A serious adverse event (SAE) is any AE which: - Resulted in death - Was life-threatening - Required inpatient hospitalization or prolongation of existing hospitalization - Resulted in persistent or significant disability/incapacity - Was a congenital anomaly/birth defect - Constituted an important medical event.
- Percentage of Participants With a Psoriatic Arthritis Response Criteria (PsARC) Response at Week 24 [ Time Frame: Baseline and Week 24 ]
A PsARC response is defined as improvement from Baseline in at least 2 of the following 4 measures, at least 1 of which must be tender joint count or swollen joint count, and no worsening in any of the 4 measures: • At least 30% improvement in the 78 tender joint count, • At least 30% improvement in the 76 swollen joint count, • At least 20% improvement in the 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; • At least 20% improvement in the physician global assessment of disease activity, measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest. Participants with missing data were considered non-responders.
- Percentage of Participants With a Modified ACR 20 Response at Week 24 [ Time Frame: Baseline (Day 1), Week 12 (Day 85) and Week 24 ]
A modified ACR 20 response was defined as a participant who met the following 3 criteria for improvement: • ≥ 20% improvement in 78 tender joint count (includes 10 additional joints often involved in psoriatic arthritis: the first carpometacarpal [CMC] and the distal interphalangeal [DIP] joints of the fingers); • ≥ 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 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. Response at Week 24 was measured as improvement from Baseline (Day 1) and from Week 12 (Day 85). Participants with no post-baseline ACR scores were considered non-responders.
- Percentage of Participants With a Modified ACR 50 Response at Week 24 [ Time Frame: Baseline (Day 1), Week 12 (Day 85) and Week 24 ]
A modified ACR 50 response was defined as a participant who met the following 3 criteria for improvement: • ≥ 50% improvement in 78 tender joint count (includes 10 additional joints often involved in psoriatic arthritis: the first carpometacarpal [CMC] and the distal interphalangeal [DIP] joints of the fingers); • ≥ 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 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. Response at Week 24 was measured as improvement from Baseline (Day 1) and from Week 12 (Day 85). Participants with no post-baseline ACR scores were considered non-responders.
- Percentage of Participants With a Modified ACR 70 Response at Week 24 [ Time Frame: Baseline (Day 1) and Week 24 ]
A modified ACR 70 response was defined as a participant who met the following 3 criteria for improvement: • ≥ 70% improvement in 78 tender joint count (includes 10 additional joints often involved in psoriatic arthritis: the first carpometacarpal [CMC] and the distal interphalangeal [DIP] joints of the fingers); • ≥ 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 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. Response at Week 24 was measured as improvement from Baseline (Day 1). Participants with no post-baseline ACR scores were considered non-responders.
- Percentage of Participants With Good or Moderate EULAR Response Based on DAS28-CRP(4) at Week 24 [ Time Frame: Baseline and Week 24 ]
The DAS28 measures the severity of disease at a specific time. DAS28-CRP(4) is derived from the following 4 variables: • 28 tender joint count, (does not include the DIP joints, the hip joint, or the joints below the knee) • 28 swollen joint count • C-reactive protein • Patient's global assessment of disease activity according to the formula: DAS28-CRP(4) = 0.56*√(TJC28) + 0.28*(SJC28) + 0.36*ln(CRP+1) + 0.014*GH + 0.96. DAS28 scores range from 0 to 9.4, where higher scores indicate more disease activity. A EULAR response reflects an improvement in disease activity based on the DAS-28 score. A Good Response is defined as an improvement (decrease) in the DAS28 > 1.2 from Baseline and attainment of a DAS28 score ≤ 3.2. A Moderate Response is defined as either: • an improvement (decrease) in the DAS28 > 0.6 and ≤ 1.2 and a DAS28 score ≤ to 5.1 or, • an improvement (decrease) in the DAS28 > 1.2 and a DAS28 score > 3.2
- Percentage of Participants With Good or Moderate EULAR Response Based on DAS28-CRP(3) at Week 24 [ Time Frame: Baseline and Week 24 ]
The DAS28 measures the severity of disease at a specific time. DAS28-CRP(3) is derived from the following 3 variables: • 28 tender joint count, (does not include the DIP joints, the hip joint, or the joints below the knee) • 28 swollen joint count • C-reactive protein (CRP) according to the formula: DAS28-CRP(3) = [0.56*√(TJC28) + 0.28*√(SJC28) + 0.36*ln(CRP+1)] * 1.10 + 1.15. DAS28 scores range from 0 to 9.4, where higher scores indicate more disease activity. A EULAR response reflects an improvement in disease activity based on the DAS-28 score. A Good Response is defined as an improvement (decrease) in the DAS28 > 1.2 from Baseline and attainment of a DAS28 score ≤ 3.2. A Moderate Response is defined as either: • an improvement (decrease) in the DAS28 > 0.6 and ≤ 1.2 and a DAS28 score ≤ to 5.1 or, • an improvement (decrease) in the DAS28 > 1.2 and a DAS28 score > 3.2
- Maximal ACR Response During the Extension Period [ Time Frame: ACR was measured at Baseline and Weeks 16, 20 and 24 ]
The ACR-N index score was calculated for each participant at each time point in the study according to the following definition: ACR-N = the lowest of the following 3 values: • percent improvement from Baseline in the 76 swollen joint count, • percent improvement from Baseline in the 78 tender joint count • median percent improvement from Baseline in the following 5 measures ◦ 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. The maximal ACR-N for each participant during the 12-week extension period was calculated, and represents the maximal ACR response achieved.
- Time to ACR 20 Response During the Study [ Time Frame: Baseline to Week 24 ]
Time to ACR 20 was measured from the first dose of apremilast to the first time a participant achieved an ACR 20 response in the treatment or extension phase. The Kaplan-Meier estimates of time to ACR 20 response were calculated for participants who had an ACR 20 response at any time during the study.
- Time to ACR 50 Response During the Treatment and Extension Phase [ Time Frame: Baseline to Week 24 ]
Time to ACR 50 response was measured from the first dose of apremilast to the first time a participant achieved an ACR 50 response in the treatment or extension phase. The Kaplan-Meier estimates of time to ACR 50 response were calculated for participants who had an ACR 50 response at any time during the study.
- Time to ACR 70 Response During the Treatment and Extension Phase [ Time Frame: Baseline to Week 24 ]
Time to ACR 70 response was measured from the first dose of apremilast to the first time a participant achieved an ACR 70 response in the treatment or extension phase. The Kaplan-Meier estimates of time to ACR 70 response were calculated for participants who had an ACR 70 response at any time during the study.
- Change From Baseline and Week 12 in Dactylitis Severity Score at Week 24 [ Time Frame: Baseline, Week 12 and Week 24 ]
Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated on a scale from 0 (no dactylitis) to 3 (severe dactylitis). The dactylitis severity score is the sum of the individual scores for each digit and ranges from 0 to 60. Change in the dactylitis severity score was assessed from Baseline (Day 1) and from Week 12 (Day 85).
- Percentage of Participants With Enthesitis in the Extension Phase [ Time Frame: Week 12 and Week 24 ]
Enthesitis is inflammation of the entheses, the sites where tendons or ligaments insert into the bone. Enthesitis is characterized by swelling, pain, and tenderness around the calcaneous, and occasionally by effusion in the bursa associated with this joint. The enthesitis assessment is an evaluation of inflammation at the insertions of the Achilles tendon into the calcaneous and of the plantar fascia into the calcaneous. Inflammation at 1 or more insertions on either the right or left side constituted a positive assessment.
- Time to Relapse of Psoriatic Arthritis After Extension Phase [ Time Frame: From Week 24 to the end of the 28-day follow-up (1) and from the date of maximal ACR until the end of the 28-day follow-up phase (2). ]
Relapse of psoriatic arthritis was defined as a 50% loss of the maximal ACR improvement during the Follow-up Phase in participants who achieved at least an ACR 20 at their Final Extension Phase (Week 24)/Early Termination Visit. The time to relapse during the Follow-up Phase was calculated from the time of maximum ACR reduction and from the date of the Final Extension Phase visit. Participants classified as responders who did not relapse were censored at the day of the last follow-up.
- Number of Participants Who Relapsed After the Extension Phase [ Time Frame: Week 24 to Week 28 (28-day follow-up period) ]
Relapse of psoriatic arthritis was defined as a 50% loss of the maximal ACR improvement during the Follow-up Phase in participants who achieved at least an ACR 20 at their Final Extension Phase/Early Termination Visit.
- Change From Baseline and Week 12 in SF-36 at Week 24 [ Time Frame: Baseline (Day 1), Week 12 (Day 85) and Week 24 ]
The Medical Outcome SF 36-Item Health Survey, Version 2 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 summary physical health score included the following subscales: physical functioning, role-physical, bodily pain, and general health. The summary mental health score included other subscales: vitality, social functioning, role-emotional, and mental health. Norm-based scores were used in analyses, calibrated so that 50 is the average score and the standard deviation equals 10, where higher scores are associated with better functioning/quality of life. Each domain is scored by summing the individual items and transforming the scores into a 0 to 100 scale. A higher change from baseline indicates an improvement in better health results or functioning.
- Change From Baseline and Week 12 in Dermatology Life Quality Index (DLQI) at Week 24 [ Time Frame: Baseline (Day 1), Week 12 (Day 85) and Week 24 ]
The DLQI is a validated, self-administered, 10-item questionnaire that measures the impact of skin disease on participants' quality of life, based on recall over the past week. Domains include symptoms, feelings, daily activities, leisure, work, personal relationships, and treatment. Each question is answered on a scale from 0 (not at all) to 3 (very much) The total score ranges from 0 to 30 where a higher score indicates that a participant's dermatological condition has a greater impact on their daily life.
- Change From Baseline and Week 12 in the Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 24 [ Time Frame: Baseline (Day 1), Week 12 (Day 85) and Week 24 ]
The HAQ-DI is a self-administered instrument consisting of 20 questions in eight categories of functioning which represent a comprehensive set of functional activities - dressing, rising, eating, walking, hygiene, reach, grip, and usual activities. Each item asks over the past week whether a particular task can be performed. For each item, there is a four-level difficulty scale that is scored from 0 to 3, representing normal (no difficulty) (0), some difficulty (1), much difficulty (2), and unable to do (3). The eight category scores are averaged into an overall HAQ-DI score on a scale from zero (no disability) to three (completely disabled).
- Change From Baseline in the Functional Assessment of Chronic Illness Therapy for Fatigue (FACIT-F) at Week 24 [ Time Frame: Baseline (Day 1), Week 12 (Day 85) and Week 24 ]
The FACIT-Fatigue is a 13 item self-administered questionnaire that assesses both the physical and functional consequences of fatigue based on recall during the past 7 days. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The total score ranges from 0 to 52 with higher scores representing less fatigue.
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- Type, frequency, severity and relationship of adverse events to CC-10004;
- Number of subjects who prematurely discontinue study medication due to any adverse event;
- Frequency of clinically significant changes in physical examination, vital signs, ECG and/or laboratory findings
- Frequency of subjects unable to withstand dose titration
- Frequency of subjects who discontinue participation in the treatment phase due to inability to withstand over adverse effects of the study medication;
- Proportion of subjects in each treatment group who meet PsARC at Day 85/early termination
- Proportion of subjects in each treatment group who achieve an ACR 50 and ACR 70 at Day 85/early termination
- Change in DAS of subjects in each treatment group at D85/early termination
- Change in PASI score at Day 85/ET
- Proportion of subjects in each treatment group who achieve >= PASI 50 at D85/ET
- Maximal ACR response during treatment
- Maximal PASI response during treatment
- Time to achieve ACR 20/50/70
- Time to achieve PASI 50
- Change in dactylitis severity score in subjects in each treatment group at D85/ET
- Proportion of subjects with and without enthesitis in each treatment group at D85/ET
- Time to relapse of psoriasis during observational follow up
- Time to relapse of psoriatic arthritis during observational follow up
- Proportion of subjects who relapse during observational follow up
- Change from baseline in QOL assessment scores at D85/ET
- Change in peripheral blood T cell, B cell and NK cell subsets
- Change in synovitis and change in inflammatory markers in synovial tissue at D85/ET
- Change in epidermal thickness and change in inflammatory markers in psoriatic skin biopsies at D85/ET
- Pharmacokinetic profile including AUC, Cmax, Tmax and relationship of PK to PD and clinical outcomes
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| Not Provided
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| Not Provided
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| Phase II Study of Apremilast (CC-10004) in Adults With in Psoriatic Arthritis
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| A Phase II, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, Efficacy and Safety Study of Two Dose Regimens of CC-10004 in Subjects With Active Psoriatic Arthritis
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| This study is to look at the preliminary efficacy and safety of 2 dose regimens of apremilast (20 mg twice a day and 40 mg once a day) versus placebo in patients with active psoriatic arthritis.
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| Prior to the implementation of Amendment 1/UK3 the study consisted of 3 phases - pre-randomization up to 35 days, up to 84 days placebo-controlled treatment and a 28-day observational follow up. After the implementation of Amendment 1/UK3, the study consisted of 4 phases - pre-randomization up to 35 days, up to 84 days treatment in the placebo controlled treatment phase, up to 84 days treatment in the active treatment extension phase and a 28 day follow up. Participants who completed the treatment phase prior to implementation of amendment 1/UK3 did not have the option of entering the extension phase.
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| Interventional
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| Phase 2
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Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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| Psoriatic Arthritis
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- Experimental: Apremilast 40 mg QD
Participants received 40 mg apremilast orally once a day (QD) for 12 weeks in the Treatment Phase. Participants who entered the Extension Phase continued to receive 40 mg apremilast QD for an additional 12 weeks.
The dose of apremilast was titrated starting at 10 mg QD during Days 1 to 3 followed by 20 mg QD during Days 4 to 7 and then 40 mg QD thereafter. A single dose reduction to 20 mg per day was allowed for participants who experienced intolerable adverse effects from study medication. Intervention: Drug: Apremilast
- Experimental: Apremilast 20 mg BID
Participants received 20 mg apremilast orally twice a day (BID) for 12 weeks in the Treatment Phase. Participants who entered the Extension Phase continued to receive 20 mg apremilast BID for an additional 12 weeks. The dose of apremilast was titrated starting at 10 mg QD during Days 1 to 3 followed by 20 mg QD during Days 4 to 7 and then 20 mg BID thereafter. A single dose reduction to 20 mg per day was allowed for participants who experienced intolerable adverse effects from study medication.
Intervention: Drug: Apremilast
- Placebo Comparator: Placebo
Participants received matching placebo to apremilast orally BID for 12 weeks during the Treatment Phase. Participants who entered the Extension Phase were re-randomized on Day 85 to receive either 40 mg apremilast QD or 20 mg apremilast BID for 12 weeks.
Intervention: Drug: Placebo
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- Schett G, Wollenhaupt J, Papp K, Joos R, Rodrigues JF, Vessey AR, Hu C, Stevens R, de Vlam KL. Oral apremilast in the treatment of active psoriatic arthritis: results of a multicenter, randomized, double-blind, placebo-controlled study. Arthritis Rheum. 2012 Oct;64(10):3156-67. doi: 10.1002/art.34627.
- Strand V, Schett G, Hu C, Stevens RM. Patient-reported Health-related Quality of Life with apremilast for psoriatic arthritis: a phase II, randomized, controlled study. J Rheumatol. 2013 Jul;40(7):1158-65. doi: 10.3899/jrheum.121200. Epub 2013 Apr 15.
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| Completed
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| 204
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| 132
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| May 9, 2009
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| May 9, 2009 (Final data collection date for primary outcome measure)
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Inclusion Criteria:
Exclusion Criteria:
History of any clinically significant cardiac, endocrinologic, pulmonary, neurologic, psychiatric, hepatic, renal, hematologic, immunologic, or other major diseases
- Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study
- Pregnant or lactating female
- History of active Mycobacterium tuberculosis infection (any subspecies) within 3 years prior to the screening visit. Infections that occurred > 3 years prior to entry must have been effectively treated.
- History of incompletely treated latent Mycobacterium tuberculosis infection (as indicated by a positive Purified Protein Derivative [PPD] skin test or in vitro test [T SPOT®.TB, QuantiFERON Gold®])
- Clinically significant abnormality on the chest x-ray (CXR) at screening
- Current erythrodermic, guttate, or pustular forms of psoriasis
- History of infected joint prosthesis within the past 5 years
- Systemic therapy for psoriasis and/or psoriatic arthritis (except for methotrexate, ≤ 10 mg/day prednisone or equivalent, and NSAIDs) including, but not limited to, sulfasalazine, leflunomide, chloroquine, hydroxychloroquine, gold compounds, parenteral corticosteroids (including intra-articular), penicillamine, cyclosporine, oral retinoids, mycophenolate mofetil, thioguanine, hydroxyurea, sirolimus, tacrolimus, azathioprine, and fumaric acid esters within 28 days of randomization and throughout the study
- Topical therapy for the treatment of psoriasis including, but not limited to topical steroids, topical vitamin A or D analog preparations, tacrolimus, pimecrolimus, or anthralin within 14 days of randomization (Note: Topical background therapy for treatment of psoriasis is allowed, except within 24 hours of a study visit, as follows: mild or moderate potency corticosteroids for treatment of the palms, face, scalp, axillae, plantar surfaces, and groin in accordance with the manufacturer's suggested usage. Nonmedicated emollients [eg, Eucerin®] and tar shampoo are also allowed.)
- Phototherapy (ultraviolet light A [UVA], narrow-band ultraviolet light B [NB-UVB], psoralens and long-wave ultraviolet radiation [PUVA]) within 28 days prior to randomization
- Etanercept use within 56 days prior to randomization
- Adalimumab, efalizumab, or infliximab use within 84 days prior to randomization
- Alefacept use within 168 days (24 weeks) prior to randomization
- Use of intra-articular corticosteroids within 28 days prior to randomization
- Use of any investigational medication within 28 days prior to randomization or 5 half-lives if known (whichever is longer)
- Any clinically significant abnormality on 12-lead electrocardiogram (ECG) at screening
- High-risk factor(s) for, or a history of, human immunodeficiency virus (HIV), hepatitis B, or hepatitis C virus infection
- History of malignancy within previous 5 years (except for treated basal-cell skin carcinoma(s) and/or fewer than 3 treated squamous-cell skin carcinomas)
- Evidence of skin conditions at the time of screening visit that would interfere with evaluations of the effect of study medication on psoriasis
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| Sexes Eligible for Study: |
All |
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| 18 Years and older (Adult, Older Adult)
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| No
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| Contact information is only displayed when the study is recruiting subjects
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| Belgium, Canada, Germany, Netherlands, United Kingdom
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| NCT00456092
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| CC-10004-PSA-001
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| Yes
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| Not Provided
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| Plan to Share IPD: |
Yes |
| Plan Description: |
De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request |
| Supporting Materials: |
Study Protocol |
| Supporting Materials: |
Statistical Analysis Plan (SAP) |
| Supporting Materials: |
Informed Consent Form (ICF) |
| Supporting Materials: |
Clinical Study Report (CSR) |
| Time Frame: |
Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study. |
| Access Criteria: |
Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below. |
| URL: |
http://www.amgen.com/datasharing |
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| Amgen
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| Not Provided
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| Amgen
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| Celgene Corporation
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| Not Provided
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| Amgen
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| June 2020
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