Overview

This trial is active, not recruiting.

Condition psoriatic arthritis
Treatments apremilast 20mg, apremilast 30mg, placebo, placebo + 20mg apremilast, placebo + 30mg apremilast
Phase phase 3
Sponsor Celgene Corporation
Start date December 2010
End date January 2013
Trial size 529 participants
Trial identifier NCT01307423, 2010-020324-22, CC-10004-PSA-005

Summary

The purpose of this study is to determine whether apremilast is safe and effective in the treatment of patients with psoriatic arthritis who have not been previously treated with DMARDs.

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

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
Apremilast 20mg twice daily, orally
apremilast 20mg CC-10004
Apremilast 20mg twice daily, orally
(Experimental)
Apremilast 30mg twice daily, orally
apremilast 30mg CC-10004
Apremilast 30mg twice daily, orally
(Placebo Comparator)
Placebo + 20mg Apremilast tablets administered twice daily
apremilast 20mg CC-10004
Apremilast 20mg twice daily, orally
placebo Placebo
Placebo
placebo + 20mg apremilast Placebo
Placebo + 20mg Apremilast
(Placebo Comparator)
Placebo + 30mg Apremilast tablets administered twice daily
apremilast 30mg CC-10004
Apremilast 30mg twice daily, orally
placebo Placebo
Placebo
placebo + 30mg apremilast Placebo
Placebo + 30 mg Apremilast

Primary Outcomes

Measure
Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 16
time frame: Baseline and Week 16

Secondary Outcomes

Measure
Change From Baseline in Health Assessment Questionnaire- Disability Index [HAQ-DI]) at Week 16
time frame: Baseline and Week 16
Percentage of Participants With an ACR 20 Response at Week 24
time frame: Baseline and Week 24
Change From Baseline in Health Assessment Questionnaire- Disability Index [HAQ-DI]) at Week 24
time frame: Baseline and Week 24
Change From Baseline in 36-item Short Form Health Survey (SF-36) Physical Functioning Domain at Week 16
time frame: Baseline and Week 16
Percentage of Participants With a Modified Psoriatic Arthritis Response Criteria (PsARC) Response at Week 16
time frame: Baseline and Week 16
Change From Baseline in Patient's Assessment of Pain at Week 16
time frame: Baseline and Week 16
Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at Week 16
time frame: Baseline and Week 16
Change From Baseline in Dactylitis Severity Score at Week 16
time frame: Baseline to Week 16
Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 16
time frame: Baseline and Week 16
Change in Baseline in the Disease Activity Score (DAS28) After 16 Weeks of Treatment
time frame: Baseline and Week 16
Change From Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 16
time frame: Baseline and Week 16
Change From Baseline in 36-item Short Form Health Survey (SF-36) Physical Functioning Domain at Week 24
time frame: Baseline and Week 24
Percentage of Participants With a Modified Psoriatic Arthritis Response Criteria (PsARC) Response at Week 24
time frame: Baseline and Week 24
Change From Baseline in Participants Assessment of Pain at Week 24
time frame: Baseline and Week 24
Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at Week 24
time frame: Baseline and Week 24
Change From Baseline in Dactylitis Severity Score at Week 24
time frame: Baseline and Week 24
Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 24
time frame: Baseline and Week 24
Change in Disease Activity Score (DAS 28) at Week 24
time frame: Baseline and Week 24
Change From Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 24
time frame: Baseline and Week 24
Percentage of Participants With ≥ 20% Improvement in Maastricht Ankylosing Spondylitis Entheses Score at Week 16
time frame: Baseline and Week 16
Percentage of Participants With Dactylitis Improvement ≥ 1 Point at Week 16
time frame: Baseline and Week 16
Percentage of Participants With Good or Moderate European League Against Rheumatism (EULAR) Response at Week 16
time frame: Baseline and Week 16
Percentage of Participants With MASES Improvement ≥ 20% at Week 24
time frame: Baseline and Week 24
Percentage of Participants With Dactylitis Improvement ≥ 1 Point at Week 24
time frame: Baseline and Week 24
Percentage of Participants With Good or Moderate EULAR Response at Week 24
time frame: Baseline and Week 24
Percentage of Participants With a ACR 50 Response at Week 16
time frame: Baseline and Week 16
Percentage of Participants With a ACR 70 Response at Week 16
time frame: Baseline and Week 16
Percentage of Participants With a ACR 50 Response at Week 24
time frame: Baseline and Week 24
Percentage of Participants With a ACR 70 Response at Week 24
time frame: Baseline and Week 24
Percentage of Participants With Pre-existing Enthesopathy Whose Maastricht Ankylosing Spondylitis Entheses Score Improves to 0 at Week 16
time frame: Baseline and Week 16
Percentage of Participants With Pre-existing Dactylitis Whose Dactylitis Severity Score Improves to 0 at Week 16
time frame: Baseline and Week 16
Percentage of Participants Achieving a MASES Score of Zero at Week 24
time frame: Baseline and Week 24
Percentage of Participants Achieving a Dactylitis Score of Zero at Week 24
time frame: Baseline and Week 24
Percentage of Participants With a ACR 20 Response at Week 52
time frame: Baseline and Week 52
Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 52
time frame: Baseline and Week 52
Change From Baseline in the SF-36v2 Physical Functioning Scale Score at Week 52
time frame: Baseline and Week 52
Percentage of Participants With a Modified PsARC Response at Week 52
time frame: Baseline and Week 52
Change From Baseline in the Participants Assessment of Pain Using the Visual Analog Scale at Week 52
time frame: Baseline and Week 52
Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at Week 52
time frame: Baseline and Week 52
Change From Baseline in the Dactylitis Severity Score at Week 52
time frame: Baseline and Week 52
Change From Baseline in the CDAI Score at Week 52
time frame: Baseline and Week 52
Change From Baseline in the DAS28 at Week 52
time frame: Baseline and Week 52
Change From Baseline in the FACIT-Fatigue Scale Score at Week 52
time frame: Baseline and Week 52
Percentage of Participants With MASES Improvement ≥ 20% at Week 52
time frame: Baseline and Week 52
Percentage of Participants With Pre-existing Dactylitis Whose Dactylitis Severity Score Improves From Baseline by ≥ 1 at Week 52
time frame: Baseline and Week 52
Percentage of Participants Achieving Good or Moderate EULAR Response at Week 52
time frame: Baseline and Week 52
Percentage of Participants With an ACR 50 Response at Week 52
time frame: Baseline and Week 52
Percentage of Participants With an ACR 70 Response at Week 52
time frame: Baseline and Week 52
Percentage of Participants With Pre-existing Enthesopathy Whose MASES Improves From Baseline to 0 at Week 52
time frame: Baseline and Week 52
Percentage of Participants With Pre-existing Dactylitis Whose Dactylitis Severity Score Improves From Baseline to 0 at Week 52
time frame: Baseline and Week 52
Number of Participants With Adverse Events
time frame: Up to 5 years

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: Subjects must satisfy the following criteria to be enrolled in the study: 1. Male or female, aged ≥ 18 years 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 (PsA, by any criteria) of ≥ 3 months duration. 5. Meet the Classification Criteria for Psoriatic Arthritis (CASPAR) criteria for PsA at time of screening. 6. Have ≥ 3 swollen AND ≥ 3 tender joints. 7. Have not been previously treated with disease-modifying antirheumatic drugs (DMARDS) (small molecules or biologics) 8. Be receiving treatment on an outpatient basis. 9. If taking oral corticosteroids, must be on a stable dose of prednisone ≤ 10 mg/day or equivalent for at least 1 month prior to screening. 10. If taking nonsteroidal anti-inflammatory drugs (NSAIDs) or narcotic analgesics, must be on stable dose for at least 2 weeks prior to screening and until they have completed the Week 24 study visit. 11. Low potency topical corticosteroids (Appendix M or locally available equivalent) will be allowed as background therapy for treatment of psoriasis on the face, axillae and groin in accordance with the manufacturers' suggested usage during the course of the study. Subjects with scalp psoriasis will be permitted to use coal tar shampoo and/or salicylic acid scalp preparations on scalp lesions. A non-medicated skin emollient (eg, Eucerin cream) will also be permitted for body lesions only. Subjects must not use these treatments within 24 hours prior to the clinic visit. 12. Meet the following laboratory criteria: - White blood cell count ≥ 3000/mm3 (≥ 3.0 x 109/L) and < 14,000/mm3 (< 14 x 109/L) - Platelet count ≥ 100,000/mm3 (≥ 100 x 109/L) - Serum creatinine ≤ 1.5 mg/dL(≤ 132.6 μmol/L) - Aspartate aminotransferase/Serum glutamic oxaloacetic transaminase (AST/SGOT) and Alanine aminotransferase/Serum glutamic pyruvic transaminase (ALT/SGPT) ≤ 2 x upper limit of normal (ULN) - Total bilirubin ≤ 2 mg/dL (≤ 34 μmol/L) - Hemoglobin ≥ 9 g/dL (≥ 5.6 mmol/L) - Hemoglobin A1c ≤ 9.0% 13. Male subjects (including those who have had a vasectomy) who engage in activity in which conception is possible must use barrier contraception (latex condom or any nonlatex condom NOT made out of natural [animal] membrane [eg, polyurethane]) while on IP and for at least 28 days after the last dose of IP. 14. Females of childbearing potential (FCBP) must have a negative pregnancy test at Screening and Baseline. FCBP who engage in activity in which conception is possible must use 2 forms of contraception while on investigational product (IP) and for at least 28 days after the last dose of IP: one highly effective form (ie, hormonal, intrauterine device [IUD], tubal ligation, vasectomized partner) and one additional form (latex condom or any nonlatex condom NOT made out of natural [animal] membrane [eg, polyurethane], diaphragm, sponge). If one highly effective form of contraception cannot be used, then 2 forms of barrier contraception must be used, ie, latex condom or any nonlatex condom NOT made out of natural (animal) membrane (eg, polyurethane) with either of the following: sponge with spermicide or diaphragm with spermicide. Exclusion Criteria: 1. History of clinically significant (as determined by the Investigator) cardiac, endocrinologic, pulmonary, neurologic, psychiatric, hepatic, renal, hematologic, immunologic disease, or other major uncontrolled disease. 2. Any condition, including the presence of laboratory abnormalities that 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 12-lead electrocardiography (ECG) at Screening. 4. Pregnant or breast feeding. 5. History of allergy to any component of the IP. 6. Hepatitis B surface antigen positive at screening. 7. Hepatitis C antibody positive at screening. 8. AST/SGOT and/or ALT/SGPT > 1.5 x ULN and total bilirubin > ULN or albumin < lower limit of normal (LLN). 9. History of positive Human Immunodeficiency Virus (HIV), or congenital or acquired immunodeficiency (eg, Common Variable Immunodeficiency Disease). 10. Active tuberculosis or a history of incompletely treated tuberculosis. 11. Clinically significant abnormality based upon chest radiograph with at least PA view (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. 12. Active substance abuse or a history of substance abuse within 6 months prior to Screening. 13. 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 at least 4 weeks prior to Screening. 14. Malignancy or history of malignancy (except for treated [ie, cured] basal cell or squamous cell in situ skin carcinomas and treated [ie, cured] cervical intraepithelial neoplasia [CIN] or carcinoma in situ of the cervix). 15. Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following randomization. 16. Erythrodermic, guttate, or pustular psoriasis. 17. Topical therapy for psoriasis, except as noted in the Inclusion Criteria, within 2 weeks of randomization (including but not limited to topical corticosteroids, topical retinoids or vitamin D analog preparations, tacrolimus, pimecrolimus, or anthralin). 18. Rheumatic autoimmune disease other than PsA, including systemic lupus erythematosis (SLE), mixed connective tissue disease (MCTD), scleroderma, or polymyositis. 19. Functional Class IV as defined by the ACR Classification of Functional Status in Rheumatoid Arthritis (Appendix Q). 20. Prior history of or current inflammatory joint disease other than PsA (eg, gout, reactive arthritis, RA, ankylosing spondylitis, Lyme disease). 21. Prior use of disease modifying antirheumatic drugs (DMARDS; small molecules or biologics). 22. Use of the following systemic therapy(ies) within 4 weeks of randomization, including but not limited to corticosteroids (except as noted in inclusion criteria), oral retinoids and fumaric acid esters. 23. Use of phototherapy within 4 weeks of randomization (ie, UVB, PUVA). 24. Previous treatment with any cell depleting therapies, including investigational agents (eg, rituximab, CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19, and anti-CD20). 25. Treatment with intravenous gamma globulin, plasmapheresis, or Prosorba® column within 6 months of baseline. 26. Any previous treatment with alkylating agents such as cyclophosphamide or chlorambucil, or with total lymphoid irradiation. 27. Prior treatment with apremilast. 28. Use of any investigational drug within 4 weeks of randomization, or 5 pharmacokinetic/ pharmacodynamic half lives, if known (whichever is longer).

Additional Information

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 Who Have Not Been Previously Treated With Disease-modifying Antirheumatic Drugs
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.
Trial information was received from ClinicalTrials.gov and was last updated in August 2015.
Information provided to ClinicalTrials.gov by Celgene Corporation.