Efficacy and Safety Study of Apremilast to Treat Active Psoriatic Arthritis

Psoriatic Arthritis Clinical Trial

— PALACE-1  

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: NCT01172938
• Other study ID #: CC-10004-PSA-002
• Status: Completed
• Phase: Phase 3
• Start date: June 2, 2010
• Est. completion date: October 27, 2016

Study information

• Verified date: June 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, specifically in improving 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: 504
• Est. completion date: October 27, 2016
• Est. primary completion date: April 27, 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) 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
Australia	Eastern Health Clinical School	Box Hill
Australia	Monash Medical Centre	Clayton	Victoria
Australia	Repatriation General Hospital	Daws Park
Australia	St Vincent's Hospital Melbourne	Fitzroy
Australia	Emeritus Research	Malvern
Austria	Medizinische Universitat Wien	Vienna
Austria	Ordination Wien Dr. Hanusch	Vienna
Austria	Kaiser-Franz-Josef Spital	Wien
Canada	Ultranova Skincare	Barrie	Ontario
Canada	MAC Research Incorporated	Hamilton	Ontario
Canada	K-W Musculoskeletal Research Inc.	Kitchener	Ontario
Canada	Saint Josephs Healthcare System	London	Ontario
Canada	Credit Valley Professional Building	Mississauga	Ontario
Canada	Hospital Maisonneuve - Rosemont	Montreal	Quebec
Canada	Institut de Rhumatologie de Montreal	Montreal	Quebec
Canada	The Arthritis Program Research Group Inc.	Newmarket	Ontario
Canada	Centre de Rhumatologie St-Louis	Sainte Foy	Quebec
Canada	Saskatoon Osteoporosis Centre	Saskatoon	Saskatchewan
Canada	Centre Hospitalier Universitaire de Sherbrooke-Hospital Fleurimont	Sherbrooke	Quebec
Canada	Nexus Clinical Research	St John's	Newfoundland and Labrador
Canada	St. Clare's Health Care Corporation of St. John's	St John's	Newfoundland and Labrador
Canada	Toronto Western Hospital	Toronto	Ontario
Canada	Probity Medical Research Inc	Waterloo	Ontario
Canada	Jude Rodrigues Private Practice	Windsor	Ontario
France	Ipros - Chr Orleans	Orleans
France	Hopital Purpan	Toulouse Cedex
Germany	Klinikum Duisburg, Wedau Kliniken	Duisburg
Germany	Friedrich-Alexander-Universiät Erlangen Nürnberg	Erlangen
Germany	Allgemeines Krankenhaus Eilbeck	Hamburg
Germany	Rheumazentrum Ruhrgebiet	Herne
Germany	Praxis Prof. Herbert Kellner	München
Hungary	Honvéd Kórház - Állami Egészségügyi Központ	Budapest
Hungary	Qualiclinic kft	Budapest
Hungary	Synexus Magyarország Kft.	Budapest
Hungary	MAV Korhaz es Rendelointezet Szolnok	Szolnok
Hungary	Veszprém Megyei Önkormányzat Csolnoky Ferenc Kórház-Rendelöintézet	Veszprém
New Zealand	P3 Research	Crofton Downs
New Zealand	Waikato hospital	Hamilton
New Zealand	Middlemore Clinical Trials	New Zealand
New Zealand	Queen Elizabeth Hospital for Rheumatic Disease	Rotorua
New Zealand	North Shore Hospital	Takapuna
New Zealand	Timaru Hospital	Timaru
Poland	Szpital Uniwersytecki im. Dr A.Jurasza	Bydgoszcz
Poland	Szpital Uniwersytecki nr 2 im. Dr Jana Biziela w Bydgoszczy	Bydgoszcz
Poland	Synexus SCM Sp. z o.o.	Gdynia
Poland	Synexus SCM Sp. z o.o.	Katowice
Poland	Wojewodzki Zespol Reumatologiczny	Sopot
Poland	Synexus SCM Sp. z o.o. Oddz. Warszawa	Warszawa
Russian Federation	Kemerovo State Medical Academy	Kemerovo
Russian Federation	Ryazan I.P. Pavlov State Medical University	Ryazan
Russian Federation	Departmental Hospital at Smolensk Station RZhD JSC	Smolensk
Russian Federation	Regional Clinical Hospital	Vladimir
Russian Federation	Voronezh Regional Clinical Hopsital #1, Voronezh State Medical Academy	Voronezh
South Africa	Groote Schuur Hospital	Cape Town
South Africa	Panorama Medical Centre	Cape Town
South Africa	Chelmsford Medical Centre 2	Durban
South Africa	Clinresco Centres Pty Ltd	Johannesburg
South Africa	The Park	Pinelands
Spain	Hospital General Universitario Gregorio Maranon	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Marques de Valdecilla	Santander
Spain	Hospital Clinico Universitario de Santiago	Santiago de Compostela
United Kingdom	Barnsley Hospital	Barnsley South Yorkshire
United Kingdom	Colchester General Hospital	Colchester
United Kingdom	West Suffolk Hospital	Edmunds
United States	Arthritis and Rheumatic Disease Specialties	Aventura	Florida
United States	Achieve Clinical Research LLC	Birmingham	Alabama
United States	Sonora Clinical Research, LLC	Boise	Idaho
United States	Coeur D'Alene Arthritis Clinic	Coeur d'Alene	Idaho
United States	Dermatology Treatment and Research Center	Dallas	Texas
United States	Altoona Center for Clinical Research	Duncansville	Pennsylvania
United States	Physicians East	Greenville	North Carolina
United States	Accurate Clinical Research Inc	Houston	Texas
United States	North Florida Dermatology	Jacksonville	Florida
United States	UCSD-Thornton Hospital	La Jolla	California
United States	Justus Fiechtner MD PC	Lansing	Michigan
United States	Arthritis and Osteoporosis Associates LLP	Lubbock	Texas
United States	St. Francis Hospital and Health Centers	Michigan City	Indiana
United States	Carolina Bone and Joint	Monroe	North Carolina
United States	Health Research of Oklahoma	Oklahoma City	Oklahoma
United States	Stanford University Medical Center	Palo Alto	California
United States	Arizona Research Center	Phoenix	Arizona
United States	University of Utah	Salt Lake City	Utah
United States	Seattle Rheumatology Associates	Seattle	Washington
United States	Arthritis Northwest Rheumatology	Spokane	Washington
United States	The Arthritis Center	Springfield	Illinois
United States	Tampa Medical Group Pa	Tampa	Florida
United States	Inland Rheumatology Clinical Trials	Upland	California
United States	Center for Clinical Studies	Webster	Texas
United States	Clinical Research Center of Reading, LLP	West Reading	Pennsylvania
United States	The Center for Rheumatology and Bone Research	Wheaton	Maryland
United States	Piedmont Medical Research Associates Inc	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Canada,  France,  Germany,  Hungary,  New Zealand,  Poland,  Russian Federation,  South Africa,  Spain,  United Kingdom, 

References & Publications (1)

Kavanaugh A, Mease PJ, Gomez-Reino JJ, Adebajo AO, Wollenhaupt J, Gladman DD, Hochfeld M, Teng LL, Schett G, Lespessailles E, Hall S. Longterm (52-week) results of a phase III randomized, controlled trial of apremilast in patients with psoriatic arthritis — 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 at Week 24. 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 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 to 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 SF-36 Physical Function 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 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 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.	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 Domain 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 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.	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 Adverse Events During the Placebo-Controlled 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). An AE is any noxious, unintended, or untoward medical occurrence, that may appear or worsen in a participant during the course of study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) was considered an AE. A serious AE (SAE) is any untoward adverse event that is fatal, life-threatening, results in persistent or significant disability or incapacity, requires or prolongs existing in-patient hospitalization, is a congenital anomaly or birth defect, or a condition that may jeopardize the patient or may require intervention to prevent one of the outcomes listed above.	Week 0 to Week 16 for placebo participants who entered early escape 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 Adverse Events During the Apremilast-Exposure Period	A TEAE is an 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 AE is any noxious, unintended, or untoward medical occurrence, that may appear or worsen in a participant during the course of study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) was considered an AE. A serious AE (SAE) is any untoward adverse event that is fatal, life-threatening, results in persistent or significant disability or incapacity, requires or prolongs existing in-patient hospitalization, is a congenital anomaly or birth defect, or a condition that may jeopardize the patient or may require intervention to prevent one of the outcomes listed above.	Baseline to Week 260; median total exposure to Apremilast was 170 weeks