PALACE 3: Efficacy and Safety Study of Apremilast to Treat Active Psoriatic Arthritis

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT01212770
First received: September 29, 2010
Last updated: December 13, 2013
Last verified: December 2013
  Purpose

The purpose of this study is to determine whether apremilast is safe and effective in the treatment of patients with psoriatic arthritis and a qualifying psoriasis lesion.

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


Condition Intervention Phase
Psoriatic Arthritis
Drug: Apremilast 20mg
Drug: Apremilast 30mg
Drug: Placebo + 20 mg Apremilast
Drug: Placebo + 30 mg Apremilast
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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 And A Qualifying Psoriasis Lesion

Resource links provided by NLM:


Further study details as provided by Celgene Corporation:

Primary Outcome Measures:
  • American College of Rheumatology 20% improvement [ Time Frame: 0 to 16 weeks of treatment ] [ Designated as safety issue: No ]
    Proportion of subjects in each treatment group who achieve the American College of Rheumatology criteria for a 20% improvement (ACR 20)


Secondary Outcome Measures:
  • Number of Participants with Adverse Events [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
  • Health Assessment Questionnaire Disability Index [HAQ-DI] [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
    Change from baseline in physical function (Health Assessment Questionnaire Disability Index [HAQ-DI]) after 16 weeks of treatment

  • ACR 20 [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Proportion of subjects who achieve the ACR 20, compared with baseline, after 24 weeks of treatment

  • [HAQ-DI] [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Change from baseline in physical function (HAQ-DI) after 24 weeks of treatment

  • Physical Function Domain Score [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
    Change from baseline in the physical function domain score of the Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) after 16 weeks of treatment

  • Psoriatic Arthritis Response Criteria (PsARC) [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
    Proportion of subjects who achieve the modified Psoriatic Arthritis Response Criteria (PsARC) after 16 weeks of treatment

  • Subjects Assessment of Pain (VAS) [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
    Change from baseline in subjects assessment of pain (VAS) after 16 weeks of treatment

  • Maastricht Ankylosing Spondylitis Entheses Score (MASES) [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
    Change from baseline in the Maastricht Ankylosing Spondylitis Entheses Score (MASES) in subjects with pre-existing enthesopathy after 16 weeks of treatment

  • Dactylitis Severity Score [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
    Change from baseline in the dactylitis severity score in subjects with pre-existing dactylitis after 16 weeks of treatment

  • Clinical Disease Activity Index (CDAI) [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
    Change from baseline in the Clinical Disease Activity Index (CDAI) after 16 weeks of treatment

  • Disease Activity Score (DAS28) [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
    Change from baseline in the Disease Activity Score (DAS28) after 16 weeks of treatment

  • Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
    Change from baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) score after 16 weeks of treatment

  • Physical Function Domain Score [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Change from baseline in the physical function domain score of the (SF-36) after 24 weeks of treatment

  • PsARC [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Proportion of subjects who achieve the modified PsARC after 24 weeks of treatment

  • Subjects Assessment of Pain (VAS) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Change from baseline in subject's assessment of pain (VAS) after 24 weeks of treatment

  • Change from baseline in the MASES in subjects with pre-existing enthesopathy [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Change from baseline in the MASES in subjects with pre-existing enthesopathy

  • Dactylitis Severity Score [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Change from baseline in the dactylitis severity score in subjects with pre-existing dactylitis after 24 weeks of treatment

  • CDAI [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Change from baseline in the CDAI after 24 weeks of treatment

  • DAS28 [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Change from baseline in the DAS28 after 24 weeks of treatment

  • FACIT-Fatigue score [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Change from baseline in the FACIT-Fatigue score after 24 weeks of treatment

  • Proportion of subjects with pre-existing enthesopathy whose MASES improves by ≥ 20% [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
    Proportion of subjects with pre-existing enthesopathy whose MASES improves by ≥ 20% after 16 weeks of treatment

  • Proportion of subjects with pre-existing dactylitis whose dactylitis severity score improves by ≥ 1 [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
    Proportion of subjects with pre-existing dactylitis whose dactylitis severity score improves by ≥ 1 after 16 weeks of treatment

  • European League Against Rheumatism (EULAR) [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
    Proportion of subjects with a good or moderate European League Against Rheumatism (EULAR) response after 16 weeks of treatment

  • Proportion of subjects with pre-existing enthesopathy whose MASES improves by ≥ 20% [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Proportion of subjects with pre-existing enthesopathy whose MASES improves by ≥ 20% after 24 weeks of treatment

  • Proportion of subjects with pre-existing dactylitis whose dactylitis severity score improves by ≥ 1 [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Proportion of subjects with pre-existing dactylitis whose dactylitis severity score improves by ≥ 1 after 24 weeks of treatment

  • EULAR Response [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Proportion of subjects with a good or moderate EULAR response after 24 weeks of treatment

  • ACR 50 [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
    Proportion of subjects who achieve an ACR 50, compared with baseline after 16 weeks of treatment

  • ACR 70 [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
    Proportion of subjects who achieve an ACR 70, compared with baseline after 16 weeks of treatment

  • ACR 50 [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Proportion of subjects who achieve an ACR 50, compared with baseline after 24 weeks of treatment

  • ACR 70 [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Proportion of subjects who achieve an ACR 70, compared with baseline after 24 weeks of treatment

  • Proportion of subjects with pre-existing enthesopathy whose MASES improves to 0 [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
    Proportion of subjects with pre-existing enthesopathy whose MASES improves to 0 after 16 weeks of treatment

  • Proportion of subjects with pre-existing dactylitis whose dactylitis severity score improves to 0 [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
    Proportion of subjects with pre-existing dactylitis whose dactylitis severity score improves to 0 after 16 weeks of treatment

  • Proportion of subjects with pre-existing enthesopathy whose MASES improves to 0 [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Proportion of subjects with pre-existing enthesopathy whose MASES improves to 0 after 24 weeks of treatment

  • Proportion of subjects with pre-existing dactylitis whose dactylitis severity score improves to 0 [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Proportion of subjects with pre-existing dactylitis whose dactylitis severity score improves to 0 after 24 weeks of treatment

  • ACR 20 [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    Proportion of subjects who achieve the ACR 20, compared with baseline, after 52 weeks of treatment

  • [HAQ-DI] [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    Change from baseline in physical function (HAQ-DI) after 52 weeks of treatment

  • Physical Function Domain Score [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    Change from baseline in the physical function domain score of the (SF-36) after 52 weeks of treatment

  • PsARC [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    Proportion of subjects who achieve the modified PsARC after 52 weeks of treatment

  • Subjects Assessment of Pain (VAS) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    Change from baseline in subjects assessment of pain (VAS) after 52 weeks of treatment

  • Change from baseline in the MASES [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    Change from baseline in the MASES in subjects with pre-existing enthesopathy after 52 weeks of treatment

  • Dactylitis severity score [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    Change from baseline in the dactylitis severity score in subjects with pre-existing dactylitis after 52 weeks of treatment

  • CDAI [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    Change from baseline in the CDAI after 52 weeks of treatment

  • DAS28 [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    Change from baseline in the DAS28 after 52 weeks of treatment

  • FACIT-Fatigue score [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    Change from baseline in the FACIT-Fatigue score after 52 weeks of treatment

  • Proportion of subjects with pre-existing enthesopathy whose MASES improves by ≥ 20% [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    Proportion of subjects with pre-existing enthesopathy whose MASES improves by ≥ 20% after 52 weeks of treatment

  • Proportion of subjects with pre-existing dactylitis whose dactylitis severity score improves by ≥ 1 [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    Proportion of subjects with pre-existing dactylitis whose dactylitis severity score improves by ≥ 1 after 52 weeks of treatment

  • EULAR response [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    Proportion of subjects with a good or moderate EULAR response after 52 weeks of treatment

  • ACR 50 [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    Proportion of subjects who achieve an ACR 50, compared with baseline after 52 weeks of treatment

  • ACR 70 [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    Proportion of subjects who achieve an ACR 70, compared with baseline, after 52 weeks of treatment

  • Proportion of subjects with pre-existing enthesopathy whose MASES improves to 0 [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    Proportion of subjects with pre-existing enthesopathy whose MASES improves to 0 after 52 weeks of treatment

  • Proportion of subjects with pre-existing dactylitis whose dactylitis severity score improves to 0 [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    Proportion of subjects with pre-existing dactylitis whose dactylitis severity score improves to 0 after 52 weeks of treatment

  • Proportion of subjects in each treatment group, whose psoriasis body surface area (BSA) at baseline was ≥ 3%, that achieves Psoriasis Area and Severity Index-75 (PASI) after 16 weeks of treatment [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
    Proportion of subjects in each treatment group, whose psoriasis body surface area (BSA) at baseline was ≥ 3%, that achieves Psoriasis Area and Severity Index-75 (PASI) after 16 weeks of treatment

  • Proportion of subjects in each treatment group, whose psoriasis body surface area (BSA) at baseline was ≥ 3%, that achieves Psoriasis Area and Severity Index-75 (PASI) after 24 weeks of treatment [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Proportion of subjects in each treatment group, whose psoriasis body surface area (BSA) at baseline was ≥ 3%, that achieves Psoriasis Area and Severity Index-75 (PASI) after 24 weeks of treatment

  • Proportion of subjects in each treatment group, whose psoriasis body surface area (BSA) at baseline was ≥ 3%, that achieves Psoriasis Area and Severity Index-75 (PASI) after 52 weeks of treatment [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    Proportion of subjects in each treatment group, whose psoriasis body surface area (BSA) at baseline was ≥ 3%, that achieves Psoriasis Area and Severity Index-75 (PASI) after 52 weeks of treatment

  • Work Limitations [ Time Frame: after 16, 24 or 52 weeks of treatment ] [ Designated as safety issue: No ]
    Change in the Work Limitations Questionnaire-25 (WLQ-25) score in each treatment group

  • Medical Outcomes Study [ Time Frame: after 16, 24 or 52 weeks treatment ] [ Designated as safety issue: No ]
    Change in the Medical Outcomes Study (MOS) Sleep score in each treatment group

  • EuroQol 5 Dimensions [ Time Frame: after 16, 24 or 52 weeks treatment ] [ Designated as safety issue: No ]
    Change in the EuroQol-5 Dimensions (EQ-5D) score in each treatment group

  • Health related quality of life [ Time Frame: after 2, 3, 4 or 5 years treatment ] [ Designated as safety issue: No ]
    Change in the Work Limitations Questionnaire-25 score, Medical Outcomes Study Sleep Score and the EuroQol-5 Dimensions score in each treatment group


Enrollment: 505
Study Start Date: September 2010
Estimated Study Completion Date: December 2016
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Apremilast 20 mg
20 mg Apremilast tablets administered twice daily for 24 weeks during the placebo-controlled phase followed by 20 mg Apremilast tablets administered twice daily for up to 4.5 years in the active treatment / long-term safety phase
Drug: Apremilast 20mg
Apremilast 20 mg twice daily, orally
Other Name: CC-10004
Experimental: Apremilast 30 mg
30 mg Apremilast tablets administered twice a day for 24 weeks during the placebo-controlled phase followed by 30 mg Apremilast tablets administered twice a day for up to 4.5 years in the active treatment / long-term safety phase orally twice daily
Drug: Apremilast 30mg
Apremilast 30 mg twice daily, orally
Other Name: CC-10004
Placebo Comparator: Placebo + 20 mg Apremilast
Placebo + 20 mg Apremilast tablets administered twice daily for 24 weeks during the placebo-controlled phase followed by 20 mg Apremilast tablets administered twice daily for up to 4.5 years in the active treatment / long-term safety phase. Subjects who do not have at least 20% improvement in their swollen and tender joint counts at Week 16 will escape to 20 mg Apremilast twice daily at Week 16
Drug: Placebo + 20 mg Apremilast
Placebo + 20 mg Apremilast
Other Names:
  • Placebo
  • CC-10004
Placebo Comparator: Placebo + 30 mg Apremilast
Placebo + 30 mg Apremilast tablets administered twice daily for 24 weeks during the placebo-controlled phase followed by 30 mg Apremilast tablets administered twice daily for up to 4.5 years in the active treatment / long-term safety phase. Subjects who do not have at least 20% improvement in their swollen and tender joint counts at Week 16 will escape to 30 mg Apremilast twice daily at Week 16.
Drug: Placebo + 30 mg Apremilast
Placebo + 30 mg Apremilast
Other Names:
  • Placebo
  • CC-10004

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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) criteria for PsA at time of screening.
  • Must have been inadequately treated by disease-modifying antirheumatic drugs (DMARDs)
  • May not have axial involvement alone
  • Concurrent Tx allowed with methotrexate, leflunomide, or sulfasalazine
  • Have ≥ 3 swollen AND ≥ 3 tender joints.
  • Males & Females must use contraception
  • Stable dose of NSAIDs, narcotics and low dose oral corticosteroids allowed.
  • Have at least one ≥2 cm psoriasis lesion

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01212770

  Show 67 Study Locations
Sponsors and Collaborators
Celgene Corporation
Investigators
Study Director: Douglas Hough, MD Celgene Corporation
  More Information

No publications provided

Responsible Party: Celgene Corporation
ClinicalTrials.gov Identifier: NCT01212770     History of Changes
Other Study ID Numbers: CC-10004-PSA-004
Study First Received: September 29, 2010
Last Updated: December 13, 2013
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
United States: Food and Drug Administration
Canada: Health Canada
Finland: Finnish Medicines Agency
Germany: Federal Institute for Drugs and Medical Devices
Italy: The Italian Medicines Agency
Lithuania: State Medicine Control Agency - Ministry of Health
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Romania: National Medicines Agency
Russia: Pharmacological Committee, Ministry of Health
Slovakia: State Institute for Drug Control
South Korea: Korea Food and Drug Administration (KFDA)
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Switzerland: Swissmedic
United Kingdom: Medicines and Healthcare Products Regulatory Agency
France: Agence Nationale de Sécurité du Médicament et des produits de santé

Keywords provided by Celgene Corporation:
Psoriatic Arthritis
Psoriasis
Arthritis
inflammation
skin condition
inflammatory cells
apremilast
CC-10004
phosphodiesterase type 4

Additional relevant MeSH terms:
Arthritis
Arthritis, Psoriatic
Joint Diseases
Musculoskeletal Diseases
Spondylarthropathies
Spondylarthritis
Spondylitis
Spinal Diseases
Bone Diseases
Psoriasis
Skin Diseases, Papulosquamous
Skin Diseases
Thalidomide
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents

ClinicalTrials.gov processed this record on April 15, 2014