PALACE 2: Efficacy and Safety Study of Apremilast to Treat Active Psoriatic Arthritis

Psoriatic Arthritis Clinical Trial

— PALACE2  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01212757
• Other study ID #: CC-10004-PSA-003
• Secondary ID: 2010-018386-32
• Status: Completed
• Phase: Phase 3
• Start date: September 27, 2010
• Est. completion date: January 25, 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.

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: 488
• Est. completion date: January 25, 2017
• Est. primary completion date: July 26, 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) 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.

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 + 20 mg Apremilast
Placebo + 20 mg Apremilast
• Placebo + 30 mg Apremilast
Placebo + 30 mg Apremilast

Locations

Country	Name	City	State
Belgium	CHU Brugmann	Bruxelles
Belgium	UZ Gent	Ghent
Belgium	UZ Leuven	Leuven
Belgium	University Hospital of Liege CHU Liege	Liège
Bulgaria	17 Diagnostic and Consulting Centre Sofia EOOD	Sofia
Bulgaria	Diagnostic and Consulting Centre 7	Sofia
Bulgaria	Diagnostic-Consultative Center Sveta Anna	Sofia
Bulgaria	Multiprofile Hospital for Active Treatment Sv. Ivan Rilski	Sofia
Bulgaria	University Multiprofile Hospital for Active Treatment ACIBADEM City Clinic Sofia	Sofia
Bulgaria	Diagnostic and Consulting Centre 4	Varna
Canada	Anna Jaroszynska Private Practice	Burlington	Ontario
Canada	Rheumatology Research Associates	Edmonton	Alberta
Canada	William Bensen's Private Practice	Hamilton	Ontario
Canada	North Bay Dermatology Center	North Bay	Ontario
Canada	Rheumatology Research Associates	Ottawa	Ontario
Canada	Wilderman Medical Clinic	Thornhill	Ontario
Canada	PerCuro Clinical Research	Victoria	British Columbia
Canada	Darryl Toth's Private Practice	Windsor	Ontario
Czechia	Revmatologie s.r.o.	Brno
Czechia	MEDIPONT PLUS s.r.o..	Ceske Budejovice
Czechia	L.K.N. Arthrocentrum s.r.o.	Hlucin
Czechia	ARTMEDI UPD s.r.o.	Hostivice
Czechia	Affidea Praha s.r.o	Praha 11
Czechia	Revmatologicky ustav	Praha 2
Czechia	Revmatologicka Ambulance	Praha 4
Czechia	Revmatologicka Ambulance	Sokolov
Czechia	PV - MEDICAL, s.r.o.	Zlin
Estonia	Parnu Hospital	Pärnu
Estonia	East Tallinn Central Hospital	Tallinn
Estonia	North Estonia Regional Hospital	Tallinn
Estonia	Clinical Research Centre Ltd	Tartu
Estonia	Tartu University Hospital	Tartu
France	Hopital Universitaire Dupuytren	Limoges
France	Fondation Hôpital Saint-Joseph	Paris
France	Groupe Hospitalier Pitié- Salpétrière	Paris
France	Hopital Lariboisiere	Paris
France	Centre Hospitalier Lyon Sud	Pierre Benite
Germany	Charite - Universitätsmedizin Berlin	Berlin
Germany	Klinikum der Johann-Wolfgang Goethe-Universität	Frankfurt
Germany	Praxis Karin Rockwitz	Goslar
Germany	Synexus Clinical Research GmbH	Leipzig
Hungary	Debreceni Egyetem Orvos- es Egeszsegtudomanyi Centrum	Debrecen
Hungary	Pest Megyei Flor Ferenc Korhaz	Kistarcsa
Hungary	Principal SMO Kft.	Makó
Italy	Azienda Ospedaliera Universitaria San Martino	Genova
Italy	Ospedale Luigi Sacco	Milano
Italy	Seconda Universita degli Studi di Napoli	Napoli
Italy	IRCCS Policlinico San Matteo	Pavia
Italy	Universita di Pisa	Pisa
Italy	Ospedale Civile Maggiore Borgo Trento	Verona
Poland	NZOZ Osteo-Medic sc A. Racewicz J. Supronik	Bialystok
Poland	Niepubliczny Zaklad Opieki Zdrowotnej REUMED	Lublin
Poland	Instytut Reumatologii im. prof. dr hab. med. Eleonory Reicher	Warsaw
Poland	Wojskowy Instytut Medyczny	Warszawa
Poland	Synexus SCM Sp. z o.o.	Wroclaw
Russian Federation	City Clinical Hospital #1 n.a. N.I.Pirogov	Moscow
Russian Federation	City Clinical Hospital #5	Nizhniy Novgorod
Russian Federation	St.Petersburg State Medical Academy n. a. I.I.Mechnikov	St. Petersburg
Russian Federation	Yaroslavl Regional Clinical Hospital	Yaroslavl
South Africa	Nelson Mandela School Of Medicine	Durban
South Africa	Greenacres Hospital	Port Elizabeth
South Africa	Jacaranda Hospital	Pretoria
Spain	Hospital Universitario de Canarias	La Laguna
Spain	Hospital General Carlos Haya	Málaga
Spain	Hospital Sierrallana	Torrelavega
Taiwan	Chung Shan Medical University Hospital	Taichung
Taiwan	Taichung Veterans General Hospital	Taichung
Taiwan	Cathay General Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei
Taiwan	National Taiwan University Hospital	Tapei
United Kingdom	Basingstoke and North Hampshire Hospital	Basingstoke
United Kingdom	Cannock Chase Hospital	Cannock
United Kingdom	Chapel Allerton Hospital	Leeds
United Kingdom	Poole Hospital	Poole
United Kingdom	Great Western Hospital	Swindon
United States	Michael Bukhalo MD SC	Arlington Hts	Illinois
United States	Arthritis and Rheumatology of Georgia	Atlanta	Georgia
United States	Associated Internal Medical Specialist, PC	Battle Creek	Michigan
United States	Arthritis Care and Diagnostic Center	Dallas	Texas
United States	Baylor Research Institute	Dallas	Texas
United States	Metroplex Clinical Research Center	Dallas	Texas
United States	Denver Arthritis Clinic	Denver	Colorado
United States	Centre For Rheumatology, Immun. And Arthritis	Fort Lauderdale	Florida
United States	Rheumatology and Immunotherapy Center	Franklin	Wisconsin
United States	Vital Research	Greensboro	North Carolina
United States	Unifour Medical Research Associatets LLC	Hickory	North Carolina
United States	Research West Incorporated	Kalispell	Montana
United States	Advanced Rheumatology	Lansing	Michigan
United States	Mayo Clinic	Rochester	Minnesota
United States	University of Rochester Medical Center	Rochester	New York
United States	DMI Research	Saint Petersburg	Florida
United States	Luckster Enterprises	San Antonio	Texas
United States	Seattle Rheumatology Associates	Seattle	Washington
United States	Tacoma Center for Arthritis Research, PS	Tacoma	Washington
United States	University of South Florida	Tampa	Florida
United States	New England Research Associates, LLC	Trumbull	Connecticut
United States	Clinical and Translational Research Center of Alabama, PC	Tuscaloosa	Alabama
United States	Rheumatic Disease Associates	Willow Grove	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

United States,  Belgium,  Bulgaria,  Canada,  Czechia,  Estonia,  France,  Germany,  Hungary,  Italy,  Poland,  Russian Federation,  South Africa,  Spain,  Taiwan,  United Kingdom, 

References & Publications (1)

Cutolo M, Myerson GE, Fleischmann RM, Lioté F, Díaz-González F, Van den Bosch F, Marzo-Ortega H, Feist E, Shah K, Hu C, Stevens RM, Poder A. A Phase III, Randomized, Controlled Trial of Apremilast in Patients with Psoriatic Arthritis: Results of the PALACE 2 Trial. J Rheumatol. 2016 Sep;43(9):1724-34. doi: 10.3899/jrheum.151376. Epub 2016 Jul 15. — 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 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	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 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.	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. A positive change from baseline score indicates an improvement.	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	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 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 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 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: 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.	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: 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.	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: 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.	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 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 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 a 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	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 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 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.	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 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 During the Placebo-Controlled Phase	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	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 TEAEs During the Apremilast-Exposure Period	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	Week 0 to week 260; overall median duration of exposure to apremilast 20 mg and 30 mg BID was 198 weeks