Study to Evaluate Safety and Effectiveness of Oral Apremilast (CC-10004) in Patients With Moderate to Severe Plaque Psoriasis (ESTEEM 1)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT01194219
First received: August 31, 2010
Last updated: May 14, 2014
Last verified: May 2014
  Purpose

This study will evaluate the effects of an experimental (being tested) study drug called apremilast. Apremilast works by lowering some of the chemicals that affect psoriasis and therefore improves the symptoms of psoriasis. The purpose of this study is to test apremilast and compare its effects to placebo (an inactive substance which contains no medicine but is in the same form as the drug). This study will test efficacy (improvement of signs and symptoms) and safety of apremilast in patients with moderate to severe psoriasis.


Condition Intervention Phase
Plaque Psoriasis
Drug: Apremilast
Drug: Placebo
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, Efficacy and Safety Study of Apremilast (CC-10004) in Subjects With Moderate to Severe Plaque Psoriasis

Resource links provided by NLM:


Further study details as provided by Celgene Corporation:

Primary Outcome Measures:
  • Psoriasis Area Severity Index-75 (PASI) score. [ Time Frame: From Baseline (pre-dose) to Week 16 ] [ Designated as safety issue: No ]
    Proportion of subjects achieving at least a 75% improvement in Psoriasis Area Severity Index score


Secondary Outcome Measures:
  • Proportion of subjects treated with either apremilast 30 mg twice a day or placebo with a static Physician Global Assessment (sPGA) score of clear (0) or almost clear (1) with at least 2 points reduction. [ Time Frame: From Baseline (pre-dose) to Week 16 ] [ Designated as safety issue: No ]
  • Percent change in percent of affected body surface area. [ Time Frame: From Baseline (pre-dose) to Week 16 ] [ Designated as safety issue: No ]
  • Percent change in the PASI score. [ Time Frame: From Baseline (pre-dose) to Week 16 ] [ Designated as safety issue: No ]
  • Proportion of subjects who achieve PASI-50. [ Time Frame: Week 16 ] [ Designated as safety issue: No ]
  • Percent change in Pruritus VAS. [ Time Frame: From Baseline (pre-dose) to Week 16 ] [ Designated as safety issue: No ]
  • Change in DLQI total score. [ Time Frame: From baseline (pre-dose) to Week 16 ] [ Designated as safety issue: No ]
  • Change in Mental Component Summary (MCS) score of SF-36. [ Time Frame: From Baseline (pre-dose) to Week 16 ] [ Designated as safety issue: No ]
  • Proportion of subjects who achieve both PASI-75 and sPGA score of clear (0) or almost clear (1) with at least 2 points reduction. [ Time Frame: From Baseline (pre-dose) to Week 16 ] [ Designated as safety issue: No ]
  • Time to loss of PASI-75 response (loss of effect) during the Randomized Treatment Withdrawal Phase [ Time Frame: Week 32 until approximately Week 52 ] [ Designated as safety issue: No ]
  • Adverse Events [ Time Frame: From the time of Informed Consent, through dosing, and for 28 days after the last dose of study medication. ] [ Designated as safety issue: Yes ]
    Number of participants with adverse events.

  • Number of subjects who prematurely discontinue Investigational Product due to an adverse event [ Time Frame: From the time of Informed Consent, through dosing, and for 28 days after the last dose of study medication. ] [ Designated as safety issue: Yes ]
  • Frequency of clinically significant changes in physical examination, vital signs, electrocardiogram, and/or laboratory findings [ Time Frame: From the time of Informed Consent, through dosing, and for 28 days after the last dose of study medication. ] [ Designated as safety issue: Yes ]
  • Psoriasis flare or rebound [ Time Frame: From the time of Informed Consent, through dosing, and for 28 days after the last dose of study medication. ] [ Designated as safety issue: Yes ]
  • Population-based pharmacokinetic estimate of systemic exposure of apremilast [ Time Frame: Sparse sampling will be collected at Weeks 24, Week 32, Week 36, Week 40, Week 44, and Week 48. ] [ Designated as safety issue: No ]
  • Explore the relationship of apremilast exposure with efficacy and safety endpoints. [ Time Frame: Sparse sampling will be collected at Weeks 24, Week 32, Week 36, Week 40, Week 44, and Week 48. ] [ Designated as safety issue: No ]

Enrollment: 844
Study Start Date: August 2010
Estimated Study Completion Date: November 2016
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Apremilast 30mg Drug: Apremilast
Apremilast 30 mg twice a day. Subjects initially randomized to apremilast 30 mg twice a day, and who demonstrate a PASI 75 response at Week 32 will be randomized (1 to 1) to either continue to receive apremilast 30 mg ) BID or to receive placebo (until effect is lost). At the time effect is lost, subjects will be treated with apremilast 30 mg twice a day for the duration of their participation in the study. Non-responders or partial responders (PASI response <75) in both arms may receive additional topical or phototherapy beginning at Week 32.
Other Names:
  • CC-10004
  • Otezla
Placebo Comparator: Placebo Drug: Apremilast
Apremilast 30 mg twice a day. Subjects initially randomized to apremilast 30 mg twice a day, and who demonstrate a PASI 75 response at Week 32 will be randomized (1 to 1) to either continue to receive apremilast 30 mg ) BID or to receive placebo (until effect is lost). At the time effect is lost, subjects will be treated with apremilast 30 mg twice a day for the duration of their participation in the study. Non-responders or partial responders (PASI response <75) in both arms may receive additional topical or phototherapy beginning at Week 32.
Other Names:
  • CC-10004
  • Otezla
Drug: Placebo
Identical matching placebo orally twice a day (BID) up to week 16 followed by Apremilast 30 mg orally BID for the duration of the study. Non-responders or partial responders (PASI response <75) in both arms may receive additional topical or phototherapy beginning at Week 32.

  Eligibility

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

Inclusion Criteria:

  1. Males or females, ≥ 18 years of age at the time of signing the informed consent document
  2. Diagnosis of chronic plaque psoriasis for at least 12 months prior to Screening

    a. Have moderate to severe plaque psoriasis at Screening and Baseline

  3. Must meet all laboratory criteria
  4. 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 as described by the Study Doctor while on study medication and for at least 28 days after taking the last dose of study medication
  5. 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 study medication and for a least 28 days after the last dose of study medication.

Exclusion Criteria:

  1. Other than psoriasis, history of any clinically significant (as determined by the Investigator) or other major uncontrolled disease.

    .

  2. Pregnant or breast feeding
  3. History of allergy to any component of the study drug
  4. Hepatitis B surface antigen positive at Screening
  5. Anti-hepatitis C antibody positive at Screening
  6. Active tuberculosis (TB) or a history of incompletely treated TB
  7. Clinically significant abnormality on 12-Lead ECG at Screening
  8. Clinically significant abnormal chest x-ray
  9. History of positive human immunodeficiency virus (HIV), or have congenital or acquired immunodeficiency
  10. Active substance abuse or a history of substance abuse within 6 months prior to Screening
  11. Bacterial infections requiring treatment with oral or injectable antibiotics, or significant viral or fungal infections, within 4 weeks of Screening
  12. 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 with no evidence of recurrence within the previous 5 years)
  13. Psoriasis flare or rebound within 4 weeks prior to Screening
  14. Evidence of skin conditions that would interfere with clinical assessments
  15. Topical therapy within 2 weeks of randomization
  16. Systemic therapy for psoriasis within 4 weeks prior to randomization
  17. Use of phototherapy within 4 weeks prior to randomization (ie, UVB, PUVA)
  18. Adalimumab, etanercept, infliximab, or certolizumab pegol within 12 weeks prior to randomization
  19. Alefacept, briakinumab, or ustekinumab within 24 weeks prior to randomization
  20. Use of any investigational drug within 4 weeks prior to randomization
  21. Prolonged sun exposure or use of tanning booths or other ultraviolet (UV) light sources
  22. Prior treatment with apremilast
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01194219

  Show 76 Study Locations
Sponsors and Collaborators
Celgene Corporation
Investigators
Study Director: Irina Khanskaya, MD Celgene Corporation
  More Information

No publications provided

Responsible Party: Celgene Corporation
ClinicalTrials.gov Identifier: NCT01194219     History of Changes
Other Study ID Numbers: CC-10004-PSOR-008
Study First Received: August 31, 2010
Last Updated: May 14, 2014
Health Authority: Canada: Health Canada
United States: Food and Drug Administration
Australia: Department of Health and Ageing Therapeutic Goods Administration
Belgium: Federal Agency for Medicinal Products and Health Products
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Celgene Corporation:
Plaque Psoriasis

Additional relevant MeSH terms:
Psoriasis
Skin Diseases, Papulosquamous
Skin Diseases
Apremilast
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Central Nervous System Agents

ClinicalTrials.gov processed this record on July 31, 2014