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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01925768




Registration number
NCT01925768
Ethics application status
Date submitted
15/08/2013
Date registered
20/08/2013

Titles & IDs
Public title
Safety and Efficacy Study of Apremilast to Treat Psoriatic Arthritis
Scientific 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
Secondary ID [1] 0 0
CC-10004-PSA-006
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Psoriatic Arthritis 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Osteoarthritis
Inflammatory and Immune System 0 0 0 0
Rheumatoid arthritis
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Apremilast 30 mg
Treatment: Drugs - Placebo

Experimental: Apremilast 30 mg - 30 mg Apremilast tablets administered twice daily (BID) for 24 weeks during the double-blind placebo-controlled phase; followed by 30 mg Apremilast BID for 28 weeks of active treatment phase (up to the 52 week visit); original treatment assignments remain blinded until all participants have completed their 52 week visit or have discontinued. After the Wk 52 visit, all participants in the extension phase will continue to receive treatment with apremilast 30 mg BID until the end of the study (ie, up to Week 104 visit) or until early discontinuation from the trial.

Placebo comparator: Placebo - Oral placebo BID during the placebo controlled phase weeks 0 to 24; placebo treated participants whose improvement is \<10% in both swollen and tender joint counts at Week 16 are eligible for early escape (based on the measure of clinical benefit from their current treatment as evidenced by improvement (or lack of improvement) in 1) the physician (evaluator's) global assessment (EGA), 2) patients pain (pain NRS), 3) the patient global assessments (PGA), and 4) the health assessment questionnaire disability index (HAQ-DI); Placebo-treated patients who early escape are transitioned to apremilast 30 mg PO BID during the active treatment phase up to their Week 52 visit; all those who complete the 52-week treatment phase will enter an open-label extension phase for an additional 52 weeks or until early discontinuation from the trial.


Treatment: Drugs: Apremilast 30 mg
30mg of Apremilast will be orally administered twice daily for 104 weeks

Treatment: Drugs: Placebo
Identically appearing Placebo tablets will be orally administered twice daily for up to 24 weeks

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants Who Achieved an American College of Rheumatology 20% (ACR20) Response at Week 16
Timepoint [1] 0 0
Baseline and Week 16
Secondary outcome [1] 0 0
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 24
Timepoint [1] 0 0
Baseline and Week 24
Secondary outcome [2] 0 0
Percentage of Participants Who Achieved an American College of Rheumatology 20% (ACR20) at Week 24
Timepoint [2] 0 0
Baseline and Week 24
Secondary outcome [3] 0 0
Change From Baseline in the 28-Joint Disease Activity Score Using C-reactive Protein as the Acute-Phase Reactant (DAS28 [CRP]) at Week 24
Timepoint [3] 0 0
Baseline and Week 24
Secondary outcome [4] 0 0
Change From Baseline in the Medical Outcomes Short Form Health Survey (SF-36) V2 Physical Function Domain Score at Week 24
Timepoint [4] 0 0
Baseline and Week 24
Secondary outcome [5] 0 0
Change From Baseline in the 36-item SF-36 Physical Component Summary Score at Week 24
Timepoint [5] 0 0
Baseline and Week 24
Secondary outcome [6] 0 0
Change From Baseline in the Duration of Morning Stiffness at Week 24
Timepoint [6] 0 0
Baseline and Week 24
Secondary outcome [7] 0 0
Percentage of Participants With Improved Change in Severity of Morning Stiffness at Week 24
Timepoint [7] 0 0
Baseline and Week 24
Secondary outcome [8] 0 0
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 16
Timepoint [8] 0 0
Baseline and Week 16
Secondary outcome [9] 0 0
Change From Baseline in the Disease Activity Score DAS28 (CRP) at Week 16
Timepoint [9] 0 0
Baseline and Week 16
Secondary outcome [10] 0 0
Change From Baseline in 36-item Short Form Health Survey (SF-36) V 2 Physical Functioning Domain at Week 16
Timepoint [10] 0 0
Baseline and Week 16
Secondary outcome [11] 0 0
Mean Change From Baseline in the Duration of Morning Stiffness at Week 16
Timepoint [11] 0 0
Baseline and Week 16
Secondary outcome [12] 0 0
Percentage of Participants Whose Severity of Morning Stiffness at Week 16 Improved From Baseline
Timepoint [12] 0 0
Baseline and Week 16
Secondary outcome [13] 0 0
Percentage of Participants Who Achieved an American College of Rheumatology 20% (ACR20) Response at Weeks 2, 4, 6, 8, 12 and 20
Timepoint [13] 0 0
Baseline and at Weeks 2, 4, 6, 8, 12 and 20
Secondary outcome [14] 0 0
Percentage of Participants Who Achieved an American College of Rheumatology 20% (ACR20) Response at Weeks 52 and 104
Timepoint [14] 0 0
Baseline and Weeks 52 and 104
Secondary outcome [15] 0 0
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Weeks 52 and 104
Timepoint [15] 0 0
Baseline and Weeks 52 and 104
Secondary outcome [16] 0 0
Change From Baseline in the Disease Activity Score (DAS28) at Week 52 and 104
Timepoint [16] 0 0
Baseline and Weeks 52 and 104
Secondary outcome [17] 0 0
Change From Baseline in 36-item SF-36 (V2.0) Physical Functioning Domain Score at Weeks 52 and 104
Timepoint [17] 0 0
Baseline and Weeks 52 and 104
Secondary outcome [18] 0 0
Change From Baseline in the Duration of Morning Stiffness at Weeks 52 and 104
Timepoint [18] 0 0
Baseline and Weeks 52 and 104
Secondary outcome [19] 0 0
Percentage of Participants Whose Severity of Morning Stiffness at Week 52 and 104 Improved From Baseline
Timepoint [19] 0 0
Baseline and Weeks 52 and 104
Secondary outcome [20] 0 0
Number of Participants With Treatment Emergent Adverse Events (TEAE) During the 24 Week Placebo Controlled Phase
Timepoint [20] 0 0
Date of first dose of study drug to Week 24; median duration of exposure during placebo controlled phase was 24.14 weeks
Secondary outcome [21] 0 0
Number of Participants With Treatment Emergent Adverse Events (TEAE) During the Apremilast-Exposure Period
Timepoint [21] 0 0
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

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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.



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).

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 0 0
Colin Bayliss Research and Teaching Unit - Victoria Park
Recruitment hospital [2] 0 0
Eastern Health Clinical School - Box Hill
Recruitment hospital [3] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [4] 0 0
Menzies Centre for Population Health Research - Hobart,
Recruitment hospital [5] 0 0
Optimus Clinical Research Pty. Ltd - Kogarah
Recruitment hospital [6] 0 0
Coastal Joint Care - Maroochydore
Recruitment hospital [7] 0 0
Westmead Cancer Care Center - Westmead, NSW
Recruitment postcode(s) [1] 0 0
6100 - Victoria Park
Recruitment postcode(s) [2] 0 0
3128 - Box Hill
Recruitment postcode(s) [3] 0 0
2050 - Camperdown
Recruitment postcode(s) [4] 0 0
7000 - Hobart,
Recruitment postcode(s) [5] 0 0
2217 - Kogarah
Recruitment postcode(s) [6] 0 0
4558 - Maroochydore
Recruitment postcode(s) [7] 0 0
2145 - Westmead, NSW
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Idaho
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
Montana
Country [8] 0 0
United States of America
State/province [8] 0 0
Nebraska
Country [9] 0 0
United States of America
State/province [9] 0 0
North Carolina
Country [10] 0 0
United States of America
State/province [10] 0 0
Pennsylvania
Country [11] 0 0
United States of America
State/province [11] 0 0
Tennessee
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
United States of America
State/province [13] 0 0
Utah
Country [14] 0 0
United States of America
State/province [14] 0 0
West Virginia
Country [15] 0 0
Canada
State/province [15] 0 0
British Columbia
Country [16] 0 0
Canada
State/province [16] 0 0
Manitoba
Country [17] 0 0
Canada
State/province [17] 0 0
Newfoundland and Labrador
Country [18] 0 0
Canada
State/province [18] 0 0
Ontario
Country [19] 0 0
Canada
State/province [19] 0 0
Quebec
Country [20] 0 0
Czechia
State/province [20] 0 0
Praha 2
Country [21] 0 0
Czechia
State/province [21] 0 0
Praha 4
Country [22] 0 0
Czechia
State/province [22] 0 0
Sokolov
Country [23] 0 0
Czechia
State/province [23] 0 0
Zlin
Country [24] 0 0
Estonia
State/province [24] 0 0
Tallinn
Country [25] 0 0
Estonia
State/province [25] 0 0
Tartu
Country [26] 0 0
Hungary
State/province [26] 0 0
Budapest
Country [27] 0 0
Hungary
State/province [27] 0 0
Debrecen
Country [28] 0 0
Hungary
State/province [28] 0 0
Szolnok
Country [29] 0 0
Hungary
State/province [29] 0 0
Veszprém
Country [30] 0 0
New Zealand
State/province [30] 0 0
Hamilton
Country [31] 0 0
New Zealand
State/province [31] 0 0
Manukau
Country [32] 0 0
New Zealand
State/province [32] 0 0
Timaru
Country [33] 0 0
Romania
State/province [33] 0 0
Bucharest
Country [34] 0 0
Romania
State/province [34] 0 0
Cluj-Napoca
Country [35] 0 0
Romania
State/province [35] 0 0
Galati
Country [36] 0 0
Romania
State/province [36] 0 0
Sfantu Gheorghe, Covasna
Country [37] 0 0
Russian Federation
State/province [37] 0 0
Kazan
Country [38] 0 0
Russian Federation
State/province [38] 0 0
Penza
Country [39] 0 0
Russian Federation
State/province [39] 0 0
Smolensk
Country [40] 0 0
Russian Federation
State/province [40] 0 0
Yaroslavl
Country [41] 0 0
Spain
State/province [41] 0 0
A Coruña
Country [42] 0 0
Spain
State/province [42] 0 0
Barcelona, Hospitalet De Llobregat
Country [43] 0 0
Spain
State/province [43] 0 0
Barcelona
Country [44] 0 0
Spain
State/province [44] 0 0
Bilbao
Country [45] 0 0
Spain
State/province [45] 0 0
La Laguna
Country [46] 0 0
Spain
State/province [46] 0 0
Madrid
Country [47] 0 0
Spain
State/province [47] 0 0
Málaga
Country [48] 0 0
Spain
State/province [48] 0 0
Sabadell
Country [49] 0 0
Spain
State/province [49] 0 0
Santiago de Compostela

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Amgen
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
MD
Address 0 0
Amgen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)
When will data be available (start and end dates)?
Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
Available to whom?
Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: http://www.amgen.com/datasharing


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.