Safety and Efficacy Study of Apremilast to Treat Psoriatic Arthritis

Psoriatic Arthritis Clinical Trial

Official title:

A Phase 3b, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Efficacy and Safety of Apremilast (CC-10004) Monotherapy in Subjects With Active Psoriatic Arthritis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01925768
• Other study ID #: CC-10004-PSA-006
• Status: Completed
• Phase: Phase 3
• Start date: September 4, 2013
• Est. completion date: November 17, 2016

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 for treating patients with psoriatic arthritis.

Description:

This is a Phase 3b, multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of apremilast monotherapy in subjects with active psoriatic arthritis.

Approximately 214 subjects will be randomized in a 1:1 ratio to either apremilast 30 mg BID (twice a day) or identically-appearing placebo, with approximately 107 subjects per treatment group.

This is a 113-week study. The subjects will spend 24 weeks in the double-blind, placebo-controlled treatment phase, followed by 28 weeks of active treatment phase (ie, up to Week 52 visit). The original treatment assignments (apremilast 30 mg BID (twice a day) or placebo) will remain blinded until all subjects have completed their Week 52 visit (or have discontinued). After the Week 52 visit, all subjects in the extension phase will continue to receive treatment with apremilast 30 mg BID (twice a day) until the end of the study (ie, up to Week 104 visit) or until early discontinuation from the trial.

The study will consist of 5 phases:

1. Screening Phase - up to 5 weeks

2. Randomized, Placebo-controlled, Double Blind Treatment Phase - Weeks 0 to 24

3. Active Treatment Phase - Week 24 to Week 52

4. Open-label Extension Phase - Week 52 to Week 104

5. Post-treatment Observational Follow-up Phase

Recruitment information / eligibility

• Status: Completed
• Enrollment: 219
• Est. completion date: November 17, 2016
• Est. primary completion date: February 25, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Males or females, 18 years and older at time of consent.

2. Must understand and voluntarily sign an informed consent document prior to any study related assessments/procedures being conducted.

3. Able to adhere to the study visit schedule and other protocol requirements.

4. Have a documented diagnosis of psoriatic arthritis (by any criteria) of at least 3 months' duration

5. Meet the classification criteria for psoriatic arthritis (CASPAR) at the time of screening.

6. Have at least 3 swollen AND at least 3 tender joints.

7. Must have high sensitivity C-Reactive Protein (hs-CRP) of at least 0.5 mg/dL at screening and at baseline.

8. Must be receiving treatment on an outpatient basis.

9. Must be tumor necrosis factor (TNF) blocker naive and other Biologic naïve for dermatologic and rheumatic conditions

10. Subjects taking disease modifying anti-rheumatoid drugs (DMARDs), with the exception of cyclosporine and leflunomide (see 7.3. Exclusion Criteria 20, 21), do not require a washout, however, they must discontinue the DMARD treatment at least one day prior to their baseline visit (ie, Visit 2, Day 0)

11. Subjects who have been previously treated with leflunomide will require a 12-week washout or treatment with the cholestyramine, per leflunomide prescribing label (ie. 8 g cholestyramine 3 times daily for 11 days.

12. Subjects who have been previously treated with cyclosporine will require a 4-week washout prior to randomization to participate in the study

13. If taking oral corticosteroids, must be on a stable dose of prednisone less than or equal to 10 mg/day or equivalent for at least 30 days prior to baseline visit (ie, Day 0)

14. If taking nonsteroidal anti-inflammatory drugs (NSAIDs) or narcotic analgesics, must be on stable dose for at least 30 days prior to baseline visit (ie, Day 0) and until they have completed the Week 24 study visit.

15. Must meet the following laboratory criteria:

• White blood cell count greater than 3000/mm^3 (greater than 3.0 X 10^9/L) and less than 14,000/mm^3 (less than 14 X 10^9/L)

• Platelet count at least 100,000/mm^3 (at least 100 X 10^9/L)

• Serum creatinine less than or equal to 1.5 mg/dL (less than or equal to 132.6 µmol/L)

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to twice upper limit of normal (ULN). If initial test shows ALT or AST greater than 2 times the ULN, one repeat test is allowed during the screening period.

• Total bilirubin less than or equal to 2 mg/dL (less than or equal to 34 µmol/L) or Albumin greater than LLN. If initial test result is greater than 2 mg/dL, one repeat test is allowed during the screening period.

• Hemoglobin at least 9 g/dL (at least 5.6 mmol/L)

• Hemoglobin A1c less than or equal to 9.0%

16. All females of childbearing potential (FCBP) must use one of the approved contraceptive options as described below while on investigational product and for at least 28 days after administration of the last dose of the investigational product.

At the time of study entry, and at any time during the study when a female subject of childbearing potential's contraceptive measures or ability to become pregnant changes, the investigator will educate the subject regarding contraception options and the correct and consistent use of effective contraceptive methods in order to successfully prevent pregnancy.

Females of childbearing potential must have a negative pregnancy test at Screening and Baseline. All FCBP subjects who engage in activity in which conception is possible must use one of the approved contraceptive options described below:

Option 1: Any one of the following highly effective methods: hormonal contraception (oral, injection, implant, transdermal patch, vaginal ring); intrauterine device (IUD); tubal ligation; or partner's vasectomy; OR Option 2: Male or female condom (latex condom or non latex condom NOT made out of natural [animal] membrane [for example, polyurethane]; PLUS one additional barrier method: (a) diaphragm with spermicide; (b) cervical cap with spermicide; or (c) contraceptive sponge with spermicide.

17. Male subjects (including those who have had a vasectomy) who engage in activity in which conception is possible must use barrier contraception (male latex condom or nonlatex condom NOT made out of natural [animal] membrane [for example, polyurethane]) while on investigational product and for at least 28 days after the last dose of investigational product.

Exclusion Criteria:

1. History of clinically significant (as determined by the investigator) cardiac, endocrine, pulmonary, neurologic, psychiatric, hepatic, renal, hematologic, immunologic disease, or other major uncontrolled disease.

2. Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.

3. Clinically significant abnormality on a 12-lead electrocardiogram (ECG) at Screening.

4. Pregnant or breast feeding.

5. History of allergy to any component of the investigational product.

6. Hepatitis B surface antigen positive at screening.

7. Hepatitis C antibody positive at screening.

8. History of positive human immunodeficiency virus (HIV), or congenital or acquired immunodeficiency (eg, Common Variable Immunodeficiency Disease).

9. Active tuberculosis or a history of incompletely treated tuberculosis.

10. Clinically significant abnormality based upon chest radiograph with at least posterior-anterior (PA) view (the radiograph must be taken within 12 weeks prior to Screening or during the Screening visit). An additional lateral view is strongly recommended but not required.

11. Active substance abuse or a history of substance abuse within 6 months prior to Screening.

12. Bacterial infections requiring treatment with oral or injectable antibiotics, or significant viral or fungal infections, within 4 weeks of Screening. Any treatment for such infections must have been completed and the infection cured, at least 4 weeks prior to Screening.

13. Malignancy or history of malignancy, except for:

1. treated [ie, cured] basal cell or squamous cell in situ skin carcinomas;

2. treated [ie, cured] cervical intraepithelial neoplasia [CIN] or carcinoma in situ of the cervix with no evidence of recurrence within the previous 5 years.

14. Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following randomization.

15. Erythrodermic, guttate, or generalized pustular psoriasis at randomization.

16. Rheumatic autoimmune disease other than PsA, including, but not limited to: systemic lupus erythematosis (SLE), mixed connective tissue disease (MCTD), scleroderma, polymyositis, or fibromyalgia.

17. Functional Class IV, as defined by the American College of Rheumatology (ACR) Classification of Functional Status in Rheumatoid Arthritis.

18. Prior history of or current inflammatory joint disease other than PsA (eg, gout, reactive arthritis, rheumatoid arthritis (RA), ankylosing spondylitis, Lyme disease).

19. Prior treatment with more than one non-biologic DMARD

20. Use of the following systemic therapy(ies) within 4 weeks of randomization:

cyclosporine or other calcineurin inhibitors, corticosteroids exceeding 10 mg daily prednisone equivalent, as well as other oral agents such as retinoids, mycophenolate, thioguanine, hydroxyurea, sirolimus, tacrolimus.

21. Use of leflunomide within 12 weeks of randomization, unless subject has taken cholestyramine, 8g TID (three times a day) x 11 days after stopping leflunomide.

22. Previous treatment with biologic agents for rheumatic diseases such as, but not limited to: adalimumab, abatacept, canakinumab, etanercept, golimumab, infliximab, rilonacept, certolizumab pegol, or tocilizumab.

23. Previous treatment with biologic agents for dermatologic diseases such as alefacept, anti-TNFs (eg etanercept, adalinumab) or ustekinumab.

24. Previous treatment with tofacitinib, Anti IL-17 agents or secukinumab

25. Previous treatment with any cell depleting therapies, including investigational agents (eg, rituximab, alemtuzumab, ocrelizumab, alemtuzumab, anti-CD4, anti-CD5, anti-CD3, anti-CD19, and anti-CD20).

26. Treatment with intravenous gamma globulin, plasmapheresis, or Prosorba® column

27. Any previous treatment with alkylating agents such as cyclophosphamide or chlorambucil, or with total lymphoid irradiation.

28. Prior treatment with any non-biologic DMARDS other than methotrexate, sulfasalazine, chloroquine, hydroxychloroquine, azathioprine, fumeric acid esters, cyclosporine, or leflunomide

29. Prior treatment with apremilast, or participation in a clinical study, involving apremilast

30. Use of any investigational drug within 4 weeks of randomization, or 5 pharmacokinetic/ pharmacodynamic half lives, if known (whichever is longer).

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Psoriatic
• Psoriatic Arthritis

Intervention

Drug:
• Apremilast 30 mg
30mg of Apremilast will be orally administered twice daily for 104 weeks
• Placebo
Identically appearing Placebo tablets will be orally administered twice daily for up to 24 weeks

Locations

Country	Name	City	State
Australia	Eastern Health Clinical School	Box Hill
Australia	Royal Prince Alfred Hospital	Camperdown
Australia	Menzies Centre for Population Health Research	Hobart,
Australia	Optimus Clinical Research Pty. Ltd	Kogarah
Australia	Coastal Joint Care	Maroochydore
Australia	Colin Bayliss Research and Teaching Unit	Victoria Park	Western Australia
Australia	Westmead Cancer Care Center	Westmead, NSW
Canada	MAC Research Incorporated	Hamilton	Ontario
Canada	CHUL du CHU de Quebec	Quebec
Canada	Karma Clinical Trials	Saint John's	Newfoundland and Labrador
Canada	Nexus Clinical Research	St John's	Newfoundland and Labrador
Canada	Arthur Karasik Private Practice	Toronto	Ontario
Canada	Manna Research	Toronto	Ontario
Canada	Manna Research	Vancouver	British Columbia
Canada	Jude Rodrigues Private Practice	Windsor	Ontario
Canada	Manitoba Clinic	Winnipeg	Manitoba
Czechia	Revmatologicky ustav	Praha 2
Czechia	Revmatologicka Ambulance	Praha 4
Czechia	Revmatologicka Ambulance	Sokolov
Czechia	PV - MEDICAL, s.r.o.	Zlin
Estonia	East Tallinn Central Hospital	Tallinn
Estonia	Innomedica Medical and Research Centre	Tallinn
Estonia	Clinical Research Centre Ltd	Tartu
Hungary	Qualiclinic kft	Budapest
Hungary	Debreceni Egyetem Orvos- es Egeszsegtudomanyi Centrum	Debrecen
Hungary	MAV Korhaz es Rendelointezet Szolnok	Szolnok
Hungary	Veszprém Megyei Önkormányzat Csolnoky Ferenc Kórház-Rendelöintézet	Veszprém
New Zealand	Waikato hospital	Hamilton
New Zealand	Middlemore Clinical Trials	Manukau
New Zealand	Timaru Hospital	Timaru
Romania	Sf. Maria Clinical Hospital	Bucharest
Romania	Emergency County Clinical Hospital	Cluj-Napoca
Romania	Sf Apostol Andrei Emergency Clinical County Hospital	Galati
Romania	SC Covamed SRL	Sfantu Gheorghe, Covasna
Russian Federation	Research Medical Complex Vashe Zdorovie	Kazan
Russian Federation	Penza Regional Clinical Hospital n.a. N.N. Burdenko	Penza
Russian Federation	Departmental Hospital at Smolensk Station RZhD JSC	Smolensk
Russian Federation	Yaroslavl Regional Clinical Hospital	Yaroslavl
Spain	Hospital Universitario a Coruna	A Coruña
Spain	Hospital Vall d'Hebron	Barcelona
Spain	Hospital Universitari de Bellvitge	Barcelona, Hospitalet De Llobregat
Spain	Hospital de Basurto-Osakidetza	Bilbao
Spain	Hospital Universitario de Canarias	La Laguna
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital General Carlos Haya	Málaga
Spain	Corporacion Sanitaria Parc Tauli	Sabadell
Spain	Hospital Clinico Universitario de Santiago	Santiago de Compostela
United States	Austin Regional Clinic	Austin	Texas
United States	Achieve Clinical Research LLC	Birmingham	Alabama
United States	Bay Area Arthritis and Osteoporosis	Brandon	Florida
United States	Health Point Medical Group	Brandon	Florida
United States	Mountain State Clinical Research	Clarksburg	West Virginia
United States	Coeur D'Alene Arthritis Clinic	Coeur d'Alene	Idaho
United States	Baylor Research Institute	Dallas	Texas
United States	Altoona Center for Clinical Research	Duncansville	Pennsylvania
United States	Physicians East	Greenville	North Carolina
United States	Palmetto Medical Research	Hialeah	Florida
United States	Houston Medical Research	Houston	Texas
United States	West Tennessee Research Institute	Jackson	Tennessee
United States	Research West Incorporated	Kalispell	Montana
United States	Advanced Rheumatology	Lansing	Michigan
United States	Arthritis and Osteoporosis Associates LLP	Lubbock	Texas
United States	Ramesh C Gupta MD	Memphis	Tennessee
United States	Jeffrey Alper MD Research	Naples	Florida
United States	Suncoast Clinical Research	New Port Richey	Florida
United States	Heartland Clinical Research, Inc.	Omaha	Nebraska
United States	Desert Medical Advances	Palm Desert	California
United States	Rockford Orthopedic Associates, LLC	Rockford	Illinois
United States	University of Utah	Salt Lake City	Utah
United States	University of South Florida	Tampa	Florida
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,  Canada,  Czechia,  Estonia,  Hungary,  New Zealand,  Romania,  Russian Federation,  Spain, 

References & Publications (1)

Nash P, Ohson K, Walsh J, Delev N, Nguyen D, Teng L, Gómez-Reino JJ, Aelion JA; ACTIVE investigators. Early and sustained efficacy with apremilast monotherapy in biological-naïve patients with psoriatic arthritis: a phase IIIB, randomised controlled trial (ACTIVE). Ann Rheum Dis. 2018 May;77(5):690-698. doi: 10.1136/annrheumdis-2017-211568. Epub 2018 Jan 17. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Who Achieved 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 self-assessment of pain (measured on a 0 to 10 unit numeric rating scale [NRS]); Patient's global self-assessment of disease activity (measured on a 0 to 10 unit NRS); Physician's global assessment of disease activity (measured on a 0 to 10 unit NRS); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]); C-Reactive Protein (CRP) Those who withdrew early or who did not have sufficient data at Week 16 were counted as non-responders.	Baseline and Week 16
Secondary	Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 24	HAQ-DI 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. A higher score indicates worse physical functioning, and a negative change from baseline indicates improvement.	Baseline and Week 24
Secondary	Percentage of Participants Who Achieved an American College of Rheumatology 20% (ACR20) 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 self-assessment of pain (measured on a 0 to 10 unit numeric rating scale [NRS]); Patient's global self-assessment of disease activity (measured on a 0 to 10 unit NRS); Physician's global assessment of disease activity (measured on a 0 to 10 unit NRS); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]); C-Reactive Protein (CRP) Those who withdrew early or who did not have sufficient data at Week 16 were counted as non-responders.	Baseline and Week 24
Secondary	Change From Baseline in the 28-Joint Disease Activity Score Using C-reactive Protein as the Acute-Phase Reactant (DAS28 [CRP]) 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 9.4. 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. A higher value indicates higher disease activity, and a negative change from baseline indicates improvement.	Baseline and Week 24
Secondary	Change From Baseline in the Medical Outcomes Short Form Health Survey (SF-36) V2 Physical Function Domain Score 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	Change From Baseline in the 36-item SF-36 Physical Component Summary Score at Week 24	The SF-36 (v 2.0) is a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The physical component summary (PCS) score includes the physical functioning, role physical, bodily pain, and general health domains. Minimum clinically important difference (MCID) for the scale scores, as well as the PCS and MCS, is defined as a 2.5-point improvement (increase) from baseline. The summary scores range from 0 to 100, with lower scores reflecting more disability, and higher scores reflecting less disability and better health. The 8 domains are regrouped into the PCS and MCS scores.	Baseline and Week 24
Secondary	Change From Baseline in the Duration of Morning Stiffness at Week 24	Morning stiffness was the participant's assessment of how long their morning stiffness lasted after first waking up in the morning, on average, during the previous week. A higher value indicates longer duration, and a negative change from baseline indicates improvement.	Baseline and Week 24
Secondary	Percentage of Participants With Improved Change in Severity of Morning Stiffness at Week 24	Morning stiffness severity was the participant's assessment of how severe their morning stiffness was after first waking up in the morning, on average, during the previous week. The severity was recorded as none, mild, moderate, moderately severe, or very severe. The response of no improvement includes subjects who had no change or worsened. Improvement is defined as the change from baseline of a more severe assessment to less severe assessment.	Baseline and Week 24
Secondary	Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 16	HAQ-DI 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. A higher score indicates worse physical functioning, and a negative change from baseline indicates improvement.	Baseline and Week 16
Secondary	Change From Baseline in the Disease Activity Score DAS28 (CRP) 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 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 9.4. 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. A negative change from baseline indicates improvement.	Baseline and Week 16
Secondary	Change From Baseline in 36-item Short Form Health Survey (SF-36) V 2 Physical Functioning Domain at Week 16	The SF-36 (v 2.0) 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	Mean Change From Baseline in the Duration of Morning Stiffness at Week 16	Morning stiffness was the participant's assessment of how long their morning stiffness lasted after first waking up in the morning, on average, during the previous week. A higher value indicates longer duration, and a negative change from baseline indicates improvement.	Baseline and Week 16
Secondary	Percentage of Participants Whose Severity of Morning Stiffness at Week 16 Improved From Baseline	Morning stiffness severity was the participant's assessment of how severe their morning stiffness was after first waking up in the morning, on average, during the previous week. The severity was recorded as none, mild, moderate, moderately severe, or very severe. Improvement is defined as the change from baseline of a more severe assessment to less severe assessment. Full Analysis Set; Participants who discontinued early prior to Week 16 and those who did not have sufficient data for a definitive determination of response status at Week 16 were counted as non-responders.	Baseline and Week 16
Secondary	Percentage of Participants Who Achieved an American College of Rheumatology 20% (ACR20) Response at Weeks 2, 4, 6, 8, 12 and 20	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 self-assessment of pain (measured on a 0 to 10 unit numeric rating scale [NRS]); Patient's global self-assessment of disease activity (measured on a 0 to 10 unit NRS); Physician's global assessment of disease activity (measured on a 0 to 10 unit NRS); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]); C-Reactive Protein (CRP)	Baseline and at Weeks 2, 4, 6, 8, 12 and 20
Secondary	Percentage of Participants Who Achieved an American College of Rheumatology 20% (ACR20) Response at Weeks 52 and 104	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 self-assessment of pain (measured on a 0 to 10 unit numeric rating scale [NRS]); Patient's global self-assessment of disease activity (measured on a 0 to 10 unit NRS); Physician's global assessment of disease activity (measured on a 0 to 10 unit NRS); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]); C-Reactive Protein (CRP)	Baseline and Weeks 52 and 104
Secondary	Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Weeks 52 and 104	HAQ-DI 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. A higher score indicates worse physical functioning, and a negative change from baseline indicates improvement.	Baseline and Weeks 52 and 104
Secondary	Change From Baseline in the Disease Activity Score (DAS28) at Week 52 and 104	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 9.4. 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. A negative change from baseline indicates improvement.	Baseline and Weeks 52 and 104
Secondary	Change From Baseline in 36-item SF-36 (V2.0) Physical Functioning Domain Score at Weeks 52 and 104	The SF-36 (v 2.0) 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 Weeks 52 and 104
Secondary	Change From Baseline in the Duration of Morning Stiffness at Weeks 52 and 104	Morning stiffness was the participant's assessment of how long their morning stiffness lasted after first waking up in the morning, on average, during the previous week. A higher value indicates longer duration, and a negative change from baseline indicates improvement.	Baseline and Weeks 52 and 104
Secondary	Percentage of Participants Whose Severity of Morning Stiffness at Week 52 and 104 Improved From Baseline	Morning stiffness severity was the participant's assessment of how severe their morning stiffness was after first waking up in the morning, on average, during the previous week. The severity was recorded as none, mild, moderate, moderately severe, or very severe. Improvement is defined as the change from baseline of a more severe assessment to less severe assessment.	Baseline and Weeks 52 and 104
Secondary	Number of Participants With Treatment Emergent Adverse Events (TEAE) During the 24 Week Placebo Controlled Phase	A 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.	Date of first dose of study drug to Week 24; median duration of exposure during placebo controlled phase was 24.14 weeks
Secondary	Number of Participants With Treatment Emergent Adverse Events (TEAE) 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). 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.	Start of lst dose of IP up to week 104: Weeks 0 to104 for those initially randomized to APR 30 mg BID, Weeks 16 -104 for PBO-treated patients who EE to APR at Week 16 and from Weeks 24-104 for PBO-treated patients who transitioned to APR at Week 24