PALACE 2: Efficacy and Safety Study of Apremilast to Treat Active Psoriatic Arthritis
- Conditions
- Psoriatic Arthritis
- Interventions
- Drug: Placebo + 20 mg Apremilast
- Registration Number
- NCT01212757
- Lead Sponsor
- Amgen
- Brief Summary
The purpose of this study is to determine whether apremilast is safe and effective in the treatment of patients with psoriatic arthritis.
Apremilast is proposed to improve signs and symptoms of psoriatic arthritis (tender and swollen joints, pain, physical function) in treated patients.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 488
- 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) PsA 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.
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo + 20 mg Apremilast Placebo + 20 mg Apremilast Placebo + 20 mg Apremilast tablets administered twice daily for 24 weeks during the placebo-controlled phase followed by 20 mg Apremilast tablets administered twice daily for up to 4.5 years in the active treatment / long-term safety phase. Subjects who do not have at least 20% improvement in their swollen and tender joint counts at Week 16 will escape to 20 mg Apremilast twice daily at Week 16 Apremilast 30mg Apremilast 30mg 30 mg Apremilast tablets administered twice a day for 24 weeks during the placebo-controlled phase followed by 30 mg Apremilast tablets administered twice a day for up to 4.5 years in the active treatment / long-term safety phase orally twice daily Apremilast 20mg Apremilast 20mg 20 mg Apremilast tablets administered twice daily for 24 weeks during the placebo-controlled phase followed by 20 mg Apremilast tablets administered twice daily for up to 4.5 years in the active treatment / long-term safety phase Placebo + 30 mg Apremilast Placebo + 30 mg Apremilast Placebo + 30 mg Apremilast tablets administered twice daily for 24 weeks during the placebo-controlled phase followed by 30 mg Apremilast tablets administered twice daily for up to 4.5 years in the active treatment / long-term safety phase. Subjects who do not have at least 20% improvement in their swollen and tender joint counts at Week 16 will escape to 30 mg Apremilast twice daily at Week 16.
- Primary Outcome Measures
Name Time Method Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 16 Baseline and Week 16 Percentage of participants with an 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
Name Time Method Change From Baseline in Patient's Assessment of Pain at Week 16 Baseline and Week 16 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.
Percentage of Participants With an ACR 20 Response at Week 24 Baseline and Week 24 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 Maastricht Ankylosing Spondylitis Entheses Score (MASES) at Week 16 Baseline and Week 16 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 Patient Assessment of Pain at Week 52 Baseline and Week 52 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 Health Assessment Questionnaire- Disability Index (HAQ-DI) at Week 16 Baseline and Week 16 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 Health Assessment Questionnaire- Disability Index (HAQ-DI) at Week 24 Baseline and Week 24 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 Dactylitis Severity Score at Week 16 Baseline and Week 16 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 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 Baseline and Week 16 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 Baseline and Week 16 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 36-item Short Form Health Survey (SF-36) Physical Functioning Domain at Week 24 Baseline and Week 24 The Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) is a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). Norm-based scores were used in analyses, calibrated so that 50 is the average score and the standard deviation equals 10. Higher scores indicate a higher level of functioning. The physical functioning domain assesses limitations in physical activities because of health problems. A positive change from Baseline score indicates an improvement.
Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 24 Baseline and Week 24 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.
Percentage of Participants With a Modified Psoriatic Arthritis Response Criteria (PsARC) Response at Week 16 Baseline and Week 16 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 With Good or Moderate European League Against Rheumatism (EULAR) Response at Week 16 Baseline and Week 16 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 Baseline and Week 24 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.
Change From Baseline in the SF-36 Physical Functioning Scale Score at Week 52 Baseline and Week 52 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 an ACR 70 Response at Week 52 Baseline and Week 52 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.
Change From Baseline in 36-item Short Form Health Survey (SF-36) Physical Functioning Domain at Week 16 Baseline and Week 16 The Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) is a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). Norm-based scores were used in analyses, calibrated so that 50 is the average score and the standard deviation equals 10. Higher scores indicate a higher level of functioning. The physical functioning domain assesses limitations in physical activities because of health problems. A positive change from Baseline score indicates an improvement.
Change From Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 16 Baseline and Week 16 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.
Change From Baseline in Patient's Assessment of Pain at Week 24 Baseline and Week 24 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 Dactylitis Severity Score at Week 24 Baseline and Week 24 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 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 Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 24 Baseline and Week 24 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 Dactylitis Improvement ≥ 1 Point at Week 24 Baseline and Week 24 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 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 a ACR 70 Response at Week 24 Baseline and Week 24 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 a ACR 20 Response at Week 52 Baseline and Week 52 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 Baseline and Week 52 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 a Modified Psoriatic Arthritis Response Criteria (PsARC) Response at Week 24 Baseline and Week 24 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.
Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at Week 24 Baseline and Week 24 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 Disease Activity Score (DAS28) at Week 24 Baseline and Week 24 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.
Percentage of Participants With Dactylitis Improvement ≥ 1 Point at Week 16 Baseline and Week 16 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 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 Baseline and Week 24 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 Achieving a MASES Score of Zero at Week 24 Week 24 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 With MASES Improvement ≥ 20% at Week 52 Baseline and Week 52 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 Baseline and Week 52 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 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 With MASES Improvement ≥ 20% at Week 16 Baseline and Week 16 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 a ACR 50 Response at Week 16 Baseline and Week 16 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: o Patient's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); o Patient's global assessment of disease activity (measured on a 100 mm VAS); o Physician's global assessment of disease activity (measured on a 100 mm VAS); o Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); o C-Reactive Protein.
Percentage of Participants With an ACR 70 Response at Week 16 Baseline and Week 16 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: o Patient's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); o Patient's global assessment of disease activity (measured on a 100 mm VAS); o Physician's global assessment of disease activity (measured on a 100 mm VAS); o Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); o C-Reactive Protein.
Percentage of Participants Achieving a Dactylitis Score of Zero at Week 24 Week 24 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 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 a Modified PsARC Response at Week 52 Baseline and Week 52 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.
Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at Week 52 Baseline and Week 52 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 Baseline and Week 52 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 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 52 Week 52 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 With an ACR 50 Response at Week 24 Baseline and Week 24 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: o Patient's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); o Patient's global assessment of disease activity (measured on a 100 mm VAS); o Physician's global assessment of disease activity (measured on a 100 mm VAS); o Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); o C-Reactive Protein.
Percentage of Participants Achieving a MASES Score of Zero at Week 16 Week 16 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 Week 16 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 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 Baseline and Week 52 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 Baseline and Week 52 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.
Percentage of Participants Achieving Good or Moderate EULAR Response at Week 52 Baseline and Week 52 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.
Change From Baseline in the FACIT-Fatigue Scale Score at Week 52 Baseline and Week 52 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 Achieving a Dactylitis Score of Zero at Week 52 Week 52 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 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 Treatment Emergent Adverse Events During the Placebo-Controlled Phase Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants (placebo participants who remained on placebo through week 24 and participants randomized to the APR 20 mg BID or APR 30 mg BID) A treatment emergent adverse event (TEAE) is an AE with a start date on or after the date of the first dose of Investigational Product (IP). The severity of each adverse event (AE) and serious AE (SAE) was assessed by the investigator and graded based on a scale from Mild - mild symptoms to Severe AEs (non-serious or serious). 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 eventPercentage of Participants With an ACR 50 Response at Week 52 Baseline and Week 52 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.
Number of Participants With TEAEs During the Apremilast-Exposure Period Week 0 to week 260; overall median duration of exposure to apremilast 20 mg and 30 mg BID was 198 weeks A treatment emergent adverse event (TEAE) is an AE with a start date on or after the date of the first dose of Investigational Product (IP). The severity of each adverse event (AE) and serious AE (SAE) was assessed by the investigator and graded based on a scale from Mild - mild symptoms to Severe AEs (non-serious or serious). 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
Trial Locations
- Locations (96)
CHU Brugmann
🇧🇪Bruxelles, Belgium
Diagnostic and Consulting Centre 4
🇧🇬Varna, Bulgaria
East Tallinn Central Hospital
🇪🇪Tallinn, Estonia
North Estonia Regional Hospital
🇪🇪Tallinn, Estonia
Pest Megyei Flor Ferenc Korhaz
🇭🇺Kistarcsa, Hungary
Niepubliczny Zaklad Opieki Zdrowotnej REUMED
🇵🇱Lublin, Poland
Principal SMO Kft.
🇭🇺Makó, Hungary
City Clinical Hospital #5
🇷🇺Nizhniy Novgorod, Russian Federation
Advanced Rheumatology
🇺🇸Lansing, Michigan, United States
Research West Incorporated
🇺🇸Kalispell, Montana, United States
Vital Research
🇺🇸Greensboro, North Carolina, United States
Metroplex Clinical Research Center
🇺🇸Dallas, Texas, United States
Baylor Research Institute
🇺🇸Dallas, Texas, United States
Arthritis Care and Diagnostic Center
🇺🇸Dallas, Texas, United States
Seattle Rheumatology Associates
🇺🇸Seattle, Washington, United States
PerCuro Clinical Research
🇨🇦Victoria, British Columbia, Canada
Centre For Rheumatology, Immun. And Arthritis
🇺🇸Fort Lauderdale, Florida, United States
Tacoma Center for Arthritis Research, PS
🇺🇸Tacoma, Washington, United States
17 Diagnostic and Consulting Centre Sofia EOOD
🇧🇬Sofia, Bulgaria
Revmatologicka Ambulance
🇨🇿Sokolov, Czechia
North Bay Dermatology Center
🇨🇦North Bay, Ontario, Canada
Clinical and Translational Research Center of Alabama, PC
🇺🇸Tuscaloosa, Alabama, United States
Associated Internal Medical Specialist, PC
🇺🇸Battle Creek, Michigan, United States
Wilderman Medical Clinic
🇨🇦Thornhill, Ontario, Canada
Unifour Medical Research Associatets LLC
🇺🇸Hickory, North Carolina, United States
L.K.N. Arthrocentrum s.r.o.
🇨🇿Hlucin, Czechia
Affidea Praha s.r.o
🇨🇿Praha 11, Czechia
PV - MEDICAL, s.r.o.
🇨🇿Zlin, Czechia
Michael Bukhalo MD SC
🇺🇸Arlington Hts, Illinois, United States
Rheumatology and Immunotherapy Center
🇺🇸Franklin, Wisconsin, United States
Ospedale Luigi Sacco
🇮🇹Milano, Italy
Multiprofile Hospital for Active Treatment Sv. Ivan Rilski
🇧🇬Sofia, Bulgaria
University of Rochester Medical Center
🇺🇸Rochester, New York, United States
UZ Leuven
🇧🇪Leuven, Belgium
Synexus Clinical Research GmbH
🇩🇪Leipzig, Germany
ARTMEDI UPD s.r.o.
🇨🇿Hostivice, Czechia
William Bensen's Private Practice
🇨🇦Hamilton, Ontario, Canada
Revmatologie s.r.o.
🇨🇿Brno, Czechia
MEDIPONT PLUS s.r.o..
🇨🇿Ceske Budejovice, Czechia
Revmatologicky ustav
🇨🇿Praha 2, Czechia
Anna Jaroszynska Private Practice
🇨🇦Burlington, Ontario, Canada
Darryl Toth's Private Practice
🇨🇦Windsor, Ontario, Canada
Praxis Karin Rockwitz
🇩🇪Goslar, Germany
Centre Hospitalier Lyon Sud
🇫🇷Pierre Benite, France
Fondation Hôpital Saint-Joseph
🇫🇷Paris, France
Universita di Pisa
🇮🇹Pisa, Italy
Klinikum der Johann-Wolfgang Goethe-Universität
🇩🇪Frankfurt, Germany
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Luckster Enterprises
🇺🇸San Antonio, Texas, United States
New England Research Associates, LLC
🇺🇸Trumbull, Connecticut, United States
Arthritis and Rheumatology of Georgia
🇺🇸Atlanta, Georgia, United States
Rheumatic Disease Associates
🇺🇸Willow Grove, Pennsylvania, United States
UZ Gent
🇧🇪Ghent, Belgium
University Hospital of Liege CHU Liege
🇧🇪Liège, Belgium
Diagnostic and Consulting Centre 7
🇧🇬Sofia, Bulgaria
University Multiprofile Hospital for Active Treatment ACIBADEM City Clinic Sofia
🇧🇬Sofia, Bulgaria
Diagnostic-Consultative Center Sveta Anna
🇧🇬Sofia, Bulgaria
Rheumatology Research Associates
🇨🇦Ottawa, Ontario, Canada
Parnu Hospital
🇪🇪Pärnu, Estonia
Groupe Hospitalier Pitié- Salpétrière
🇫🇷Paris, France
Clinical Research Centre Ltd
🇪🇪Tartu, Estonia
Hopital Universitaire Dupuytren
🇫🇷Limoges, France
Tartu University Hospital
🇪🇪Tartu, Estonia
Debreceni Egyetem Orvos- es Egeszsegtudomanyi Centrum
🇭🇺Debrecen, Hungary
Hopital Lariboisiere
🇫🇷Paris, France
Charite - Universitätsmedizin Berlin
🇩🇪Berlin, Germany
Azienda Ospedaliera Universitaria San Martino
🇮🇹Genova, Italy
Seconda Universita degli Studi di Napoli
🇮🇹Napoli, Italy
IRCCS Policlinico San Matteo
🇮🇹Pavia, Italy
Instytut Reumatologii im. prof. dr hab. med. Eleonory Reicher
🇵🇱Warsaw, Poland
Ospedale Civile Maggiore Borgo Trento
🇮🇹Verona, Italy
NZOZ Osteo-Medic sc A. Racewicz J. Supronik
🇵🇱Bialystok, Poland
Wojskowy Instytut Medyczny
🇵🇱Warszawa, Poland
Synexus SCM Sp. z o.o.
🇵🇱Wroclaw, Poland
City Clinical Hospital #1 n.a. N.I.Pirogov
🇷🇺Moscow, Russian Federation
St.Petersburg State Medical Academy n. a. I.I.Mechnikov
🇷🇺St. Petersburg, Russian Federation
Yaroslavl Regional Clinical Hospital
🇷🇺Yaroslavl, Russian Federation
Nelson Mandela School Of Medicine
🇿🇦Durban, South Africa
Greenacres Hospital
🇿🇦Port Elizabeth, South Africa
Jacaranda Hospital
🇿🇦Pretoria, South Africa
Taichung Veterans General Hospital
🇨🇳Taichung, Taiwan
Hospital Universitario de Canarias
🇪🇸La Laguna, Spain
Hospital Sierrallana
🇪🇸Torrelavega, Spain
Hospital General Carlos Haya
🇪🇸Málaga, Spain
Chung Shan Medical University Hospital
🇨🇳Taichung, Taiwan
Cathay General Hospital
🇨🇳Taipei, Taiwan
Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan
National Taiwan University Hospital
🇨🇳Tapei, Taiwan
Cannock Chase Hospital
🇬🇧Cannock, United Kingdom
Basingstoke and North Hampshire Hospital
🇬🇧Basingstoke, United Kingdom
Poole Hospital
🇬🇧Poole, United Kingdom
Chapel Allerton Hospital
🇬🇧Leeds, United Kingdom
Great Western Hospital
🇬🇧Swindon, United Kingdom
Denver Arthritis Clinic
🇺🇸Denver, Colorado, United States
DMI Research
🇺🇸Saint Petersburg, Florida, United States
University of South Florida
🇺🇸Tampa, Florida, United States