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

Psoriatic Arthritis Clinical Trial

— PALACE 3  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01212770
• Other study ID #: CC-10004-PSA-004
• Status: Completed
• Phase: Phase 3
• Start date: September 30, 2010
• Est. completion date: February 9, 2017

Study information

• Verified date: April 2020
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether apremilast is safe and effective in the treatment of patients with psoriatic arthritis and a qualifying psoriasis lesion.

Apremilast is proposed to improve signs and symptoms of psoriatic arthritis (tender and swollen joints, pain, physical function) in treated patients.

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 information / eligibility

• Status: Completed
• Enrollment: 505
• Est. completion date: February 9, 2017
• Est. primary completion date: August 21, 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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) criteria for PsA at time of screening.

• Must have been inadequately treated by disease-modifying antirheumatic drugs (DMARDs)

• May not have axial involvement alone

• Concurrent Tx allowed with methotrexate, leflunomide, or sulfasalazine

• Have = 3 swollen AND = 3 tender joints.

• Males & Females must use contraception

• Stable dose of 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

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Psoriatic
• Psoriatic Arthritis

Intervention

Drug:
• Apremilast 20mg
Apremilast 20 mg twice daily, orally
• Apremilast 30mg
Apremilast 30 mg twice daily, orally
• Placebo

Locations

Country	Name	City	State
Australia	Royal Prince Alfred Hospital	Camperdown
Australia	Skin Cancer Foundation	Carlton
Australia	Coff's Clinical Trials	Coffs Harbour
Australia	Heidelberg Repatriation Hospital	Heidelberg
Australia	Menzies Centre for Population Health Research	Hobart
Australia	Optimus Clinical Research Pty. Ltd	Kogarah
Australia	Coastal Joint Care	Maroochydore
Australia	The Queen Elizabeth Hospital	Woodville
Canada	Niagara Peninsula Arthritis Centre Inc.	St Catharines	Ontario
Canada	Alpha Clinical Research, LLC	St John's	Newfoundland and Labrador
Canada	Manna Research	Toronto	Ontario
Canada	Arthritis Research Centre of Canada	Vancouver	British Columbia
Canada	PerCuro Clinical Research	Victoria	British Columbia
Canada	Arthritis Centre	Winnipeg	Manitoba
Canada	Manitoba Clinic	Winnipeg	Manitoba
Finland	Helsingin Reumakeskus Oy	Helsinki
Finland	Helsingin yliopistollinen keskussairaala	Helsinki
Finland	Finnish Medical Research Co	Pori
France	Centre Hospitalier Sud Francilien - Site Gilles de Corbeil	Corbeil Essonnes
France	Hôtel-Dieu	Nantes
France	Groupe Hospitalier Archet I et II	Nice
France	Hopital Larrey Universite Paul Sabatier	Toulouse
Germany	Charite - Universitätsmedizin Berlin	Berlin
Germany	Klinische Forschung Berlin - Buch GmbH	Berlin
Germany	Klinikum der Friedrich-Schiller-Universität Jena	Jena
Germany	Universitätsmedizin der Johannes Gutenberg-Universität Mainz	Mainz
Italy	Azienda Ospedaliero-Universitaria di Bologna - Policlinico S.Orsola-Malpighi	Bologna
Italy	Fondazione PTV Policlinico Tor Vergata	Roma
Korea, Republic of	Hallym University Sacred Heart Hospital	Anyang, Kyunggi
Korea, Republic of	Chungnam National University Hospital	DaeJeon
Korea, Republic of	Gachon University Gil Medical Center	Incheon
Korea, Republic of	Inha University Hosiptal	Incheon
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital	Seoul
Korea, Republic of	Ajou University Hospital	Suwon
Lithuania	Hospital of Lithuanian University Health and Sciences	Kaunas
Lithuania	Klaipeda University Hospital	Klaipeda
Lithuania	Panevezys Hospital	Panevezys
Lithuania	Siauliai Hospital	Siauliai
Poland	Gabinet Internistyczno-Reumatologiczny Piotr Adrian Klimiuk	Bialystok
Poland	Centrum Medyczne Silesiana Sp. z o.o.	Bytom
Poland	Malopolskie Centrum Medyczne S.C.	Kraków
Poland	Prywatna Praktyka Lekarska Pawel Hrycaj	Poznan
Poland	REUMATIKA-Centrum Reumatologii Niepubliczny Zaklad Opieki Zdrowotnej	Warszawa
Romania	Baia Mare, Emergency County Hospital "Dr. Constantin Opris"	Baia Mare
Romania	SC Duo Medical SRL	Bucharest
Romania	Sf. Maria Clinical Hospital	Bucharest
Romania	Emergency County Clinical Hospital	Cluj-Napoca
Romania	Sf Apostol Andrei Emergency Clinical County Hospital	Galati
Romania	C.M.I. Dr. Ciornohuz Adriana	Iasi
Russian Federation	Sverdlovsk Regional Clinical Hospital 1	Ekaterinburg
Russian Federation	Research Medical Complex Vashe Zdorovie	Kezch
Russian Federation	Research Institute of Clinical and Experimental Lymphology	Novosibirsk
Russian Federation	Penza Regional Clinical Hospital n.a. N.N. Burdenko	Penza
Russian Federation	City Hospital 26	St. Petersburg
Slovakia	Narodny ustav reumatickych chorob	Piestany
Slovakia	MUDr. Zuzana Cizmarikova, s.r.o.	Poprad,Spisska Sobota
Slovakia	REUMEX s.r.o.	Rimavska Sobota
Spain	Hospital Universitario a Coruna	A Coruña
Spain	Hospital de Basurto-Osakidetza	Bilbao
Spain	Hospital Universitario Reina Sofia	Córdoba
Spain	Hospital Universitario Central de Asturias	Oviedo
Spain	Hospital Infanta Sofia	San Sebastian de los Reyes
Switzerland	HFR Fribourg - Hôpital Cantonal	Fribourg
Switzerland	Chuv Bh-04	Lausanne
Switzerland	Kantonsspital St. Gallen	St. Gallen
United Kingdom	Haywood Hospital	Burslem
United Kingdom	Southampton General Hospital	Southampton
United States	Austin Dermatology Associates	Austin	Texas
United States	Austin Regional Clinic	Austin	Texas
United States	Bakersfield Dermatology and Skin Cancer Medical Group	Bakersfield	California
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Joao Nascimento, MD	Bridgeport	Connecticut
United States	STAT Research, Inc.	Dayton	Ohio
United States	In Vivo Clinical Research	Doral	Florida
United States	Duke University Medical Center	Durham	North Carolina
United States	Center for Clinical Studies	Houston	Texas
United States	Houston Medical Research	Houston	Texas
United States	Dawes Fretzin Clinical Research Group, LLC	Indianapolis	Indiana
United States	West Tennessee Research Institute	Jackson	Tennessee
United States	Dermatology Research Associates	Los Angeles	California
United States	DermResearch, PLLC	Louisville	Kentucky
United States	Suncoast Clinical Research	New Port Richey	Florida
United States	Rheumatology Associates of Long Island	Orlando	Florida
United States	Desert Medical Advances	Palm Desert	California
United States	Elite Clinical Studies, LLC	Phoenix	Arizona
United States	Advent Clinical Research	Pinellas Park	Florida
United States	Rockford Orthopedic Associates, LLC	Rockford	Illinois
United States	Texas Research Center	Sugar Land	Texas
United States	Catalina Pointe Clinical Research Incorporated	Tucson	Arizona
United States	Clinical Pharmacology Study Group	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Finland,  France,  Germany,  Italy,  Korea, Republic of,  Lithuania,  Poland,  Romania,  Russian Federation,  Slovakia,  Spain,  Switzerland,  United Kingdom, 

References & Publications (1)

Edwards CJ, Blanco FJ, Crowley J, Birbara CA, Jaworski J, Aelion J, Stevens RM, Vessey A, Zhan X, Bird P. Apremilast, an oral phosphodiesterase 4 inhibitor, in patients with psoriatic arthritis and current skin involvement: a phase III, randomised, contro — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 16	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.	Baseline and Week 16
Secondary	Change From Baseline in Health Assessment Questionnaire- Disability Index (HAQ-DI) at 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.	Baseline and Week 16
Secondary	Percentage of Participants With an ACR 20 Response at 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.	Baseline and Week 24
Secondary	Change From Baseline in Health Assessment Questionnaire- Disability Index (HAQ-DI) at 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.	Baseline and Week 24
Secondary	Change From Baseline in 36-item Short Form Health Survey (SF-36) Physical Functioning Domain at 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.	Baseline and Week 16
Secondary	Percentage of Participants With a Modified Psoriatic Arthritis Response Criteria (PsARC) Response at 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.	Baseline and Week 16
Secondary	Percentage of Participants Achieving a = 75% Improvement in Psoriasis Area and Severity Index Score (PASI75) at Week 16	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.	Baseline and Week 16
Secondary	Change From Baseline in Patient's Assessment of Pain at 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.	Baseline and Week 16
Secondary	Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at 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.	Baseline and Week 16
Secondary	Change From Baseline in Dactylitis Severity Score at Week 16	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.	Baseline and Week 16
Secondary	Change From Baseline in Clinical Disease Activity Index (CDAI) at 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.	Baseline and Week 16
Secondary	Change From Baseline in the Disease Activity Score (DAS28) at 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.	Baseline and Week 16
Secondary	Change From Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at 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.	Baseline and Week 16
Secondary	Change From Baseline in 36-item Short Form Health Survey (SF-36) Physical Functioning Domain at 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.	Baseline and Week 24
Secondary	Percentage of Participants With a Modified Psoriatic Arthritis Response Criteria (PsARC) Response at 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.	Baseline and Week 24
Secondary	Percentage of Participants Achieving a = 75% Improvement in Psoriasis Area and Severity Index Score (PASI75) at Week 24	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.	Baseline and Week 24
Secondary	Change From Baseline in Patient's Assessment of Pain at 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.	Baseline and week 24
Secondary	Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at 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.	Baseline and week 24
Secondary	Change From Baseline in Dactylitis Severity Score at 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 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.	Baseline and Week 24
Secondary	Change From Baseline in Clinical Disease Activity Index (CDAI) at 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.	Baseline and Week 24
Secondary	Change From Baseline in the Disease Activity Score (DAS28) at 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.	Baseline and Week 24
Secondary	Change From Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at 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.	Baseline and Week 24
Secondary	Percentage of Participants With MASES Improvement = 20% at 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.	Baseline and Week 16
Secondary	Percentage of Participants With Dactylitis Improvement = 1 Point at 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 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.	Baseline and Week 16
Secondary	Percentage of Participants With Good or Moderate European League Against Rheumatism (EULAR) Response at 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.	Baseline and Week 16
Secondary	Percentage of Participants With MASES Improvement = 20% at 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.	Baseline and Week 24
Secondary	Percentage of Participants With Dactylitis Improvement = 1 Point at 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 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.	Baseline and Week 24
Secondary	Percentage of Participants With Good or Moderate EULAR Response at 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.	Baseline and Week 24
Secondary	Percentage of Participants With a ACR 50 Response at 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: ? 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.	Baseline and Week 16
Secondary	Percentage of Participants With an ACR 70 Response at 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: ? 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.	Baseline and Week 16
Secondary	Percentage of Participants With an ACR 50 Response at 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: ? 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.	Baseline and Week 24
Secondary	Percentage of Participants With a ACR 70 Response at 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.	Baseline and Week 24
Secondary	Percentage of Participants Achieving a MASES Score of Zero at 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.	Week 16
Secondary	Percentage of Participants Achieving a Dactylitis Score of Zero at 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 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.	Week 16
Secondary	Percentage of Participants Achieving a MASES Score of Zero at 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.	Week 24
Secondary	Percentage of Participants Achieving a Dactylitis Score of Zero at 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 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.	Week 24
Secondary	Percentage of Participants With an ACR 20 Response at 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.	Baseline and Week 52
Secondary	Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at 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.	Baseline and Week 52
Secondary	Change From Baseline in the SF-36 Physical Functioning Scale Score at 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.	Baseline and Week 52
Secondary	Percentage of Participants With a Modified PsARC Response at 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.	Baseline and Week 52
Secondary	Percentage of Participants Achieving a = 75% Improvement in Psoriasis Area and Severity Index Score (PASI75) at Week 52	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.	Baseline and Week 52
Secondary	Change From Baseline in the Patient Assessment of Pain at 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.	Baseline and Week 52
Secondary	Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at 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.	Baseline and Week 52
Secondary	Change From Baseline in the Dactylitis Severity Score at 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 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.	Baseline and Week 52
Secondary	Change From Baseline in the CDAI Score at 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.	Baseline and Week 52
Secondary	Change From Baseline in the DAS28 at 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.	Baseline and Week 52
Secondary	Change From Baseline in the FACIT-Fatigue Scale Score at 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.	Baseline and Week 52
Secondary	Percentage of Participants With MASES Improvement = 20% at 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.	Baseline and Week 52
Secondary	Percentage of Participants With Dactylitis Improvement = 1 Point at 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 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.	Baseline and Week 52
Secondary	Percentage of Participants Achieving Good or Moderate EULAR Response at 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. Two-sided 95% confidence interval is based on the Clopper-Pearson method.	Baseline and Week 52
Secondary	Percentage of Participants With an ACR 50 Response at 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.	Baseline and Week 52
Secondary	Percentage of Participants With an ACR 70 Response at 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.	Baseline and Week 52
Secondary	Percentage of Participants Achieving a MASES Score of Zero at 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.	Week 52
Secondary	Percentage of Participants Achieving a Dactylitis Score of Zero at 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 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.	Week 52
Secondary	Number of Participants With Treatment Emergent Adverse Events (TEAEs) During the Placebo-Controlled Phase	A TEAE is an adverse event (AE) with a start date on or after the date of the first dose of investigational product (IP) and no later than 28 days after the last dose of IP. An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. A serious AE is any AE that results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or constitutes an important medical event. For both AEs and SAEs the investigator assessed the severity of the event according to the grading scale: Mild: asymptomatic or with mild symptoms, Moderate: symptoms causing moderate discomfort or Severe: symptoms causing severe discomfort or pain.	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)
Secondary	Number of Participants With Treatment Emergent Adverse Events During the Apremilast Exposure Period	A TEAE is an adverse event (AE) with a start date on or after the date of the first dose of investigational product (IP) and no later than 28 days after the last dose of IP. An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. A serious AE is any AE that results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or constitutes an important medical event. For both AEs and SAEs the investigator assessed the severity of the event according to the grading scale: Mild: asymptomatic or with mild symptoms, Moderate: symptoms causing moderate discomfort or Severe: symptoms causing severe discomfort or pain.	Week 0 to Week 260; median duration of exposure to apremilast 20 mg BID was 121.71 weeks and 232.50 weeks for apremilast 30 mg BID