Efficacy and Safety Study of Apremilast (CC-10004) in Subjects With Moderate-to-Severe Plaque-Type Psoriasis (Core Study)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT00773734
First received: October 14, 2008
Last updated: May 6, 2014
Last verified: May 2014
  Purpose

The purpose of this study is to test if the study drug apremilast is safe, if it helps improve psoriasis, and how subjects tolerate it.


Condition Intervention Phase
Psoriasis
Plaque-type Psoriasis
Drug: Apremilast 10mg
Drug: Apremilast 20mg
Drug: Apremilast 30 mg
Drug: Placebo
Drug: Apremilast 30mg
Phase 2

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 2B, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging, Efficacy and Safety Study of Apremilast (CC-10004) in Subjects With Moderate-to-Severe Plaque-Type Psoriasis (Core Study)

Resource links provided by NLM:


Further study details as provided by Celgene Corporation:

Primary Outcome Measures:
  • Proportion of subjects treated with oral apremilast (10 mg BID, 20 mg BID, and 30 mg BID) who achieve a Psoriasis Area and Severity Index (PASI)-75 at Week 16 (Final Treatment Visit) [ Time Frame: From Baseline to week 16 ] [ Designated as safety issue: No ]
    Proportion of subjects treated with oral apremilast (10 mg BID, 20 mg BID, and 30 mg BID) who achieve a Psoriasis Area and Severity Index (PASI)-75 at Week 16 (Final Treatment Visit) in reference to the Baseline Visit compared with placebo


Secondary Outcome Measures:
  • Safety (type, frequency, severity, and relationship of adverse events to apremilast) [ Time Frame: From Date of Informed Consent to End of Follow-up ] [ Designated as safety issue: Yes ]
    Number of treatment emergent adverse events related to apremilast

  • Proportion of subjects who achieve PASI-75 at Week 24 [ Time Frame: From Baseline to Week 24 ] [ Designated as safety issue: No ]
    Proportion of subjects who achieve PASI-75 from baseline to week 24

  • Proportion of subjects who achieve PASI-50, PASI-90 and PASI-100 at Weeks 16 and 24 [ Time Frame: From Baseline to either week 16 or week 24 ] [ Designated as safety issue: No ]
    Proportion of subjects who achieve PASI-50, PASI-90 and PASI-100 at Weeks 16 and 24 form baseline to either week 16 or week 24

  • Time to achieve PASI-50 , PASI-75 , PASI-90 and PASI-100 during the treatment phase [ Time Frame: From baseline to end of treatment ] [ Designated as safety issue: No ]
    Time to achieve PASI-50 , PASI-75 , PASI-90 and PASI-100 from baseline to end of treatment

  • Percent change from baseline PASI at Weeks 16 and 24 [ Time Frame: From baseline to week 16 and week 24 ] [ Designated as safety issue: No ]
    Percent change from baseline PASI from baseline to 16 and 24

  • Shift change (1 or more points on a 0 to 5 point scale) in static Physician Global Assessment (sPGA) at Week 16 and 24 [ Time Frame: From baseline to week 16 and 24 ] [ Designated as safety issue: No ]
    : Shift change (1 or more points on a 0 to 5 point scale) in static Physician Global Assessment (sPGA) from baseline to Week 16 and 24

  • Percent change from baseline in percent of affected body surface area (BSA) during the treatment phase [ Time Frame: From baseline to end of treatment ] [ Designated as safety issue: No ]
    Percent change from baseline in percent of affected body surface area (BSA) from baseline to end of treatment

  • Quality of Life Questionnaire: Medical Outcome Study Short Form 36-Item Health Survey (SF-36), Version 2 at Week 16 and 24 [ Time Frame: Baseline to week 16 and 24 ] [ Designated as safety issue: No ]
    Change from baseline in reference to the QOL instrument: Medical Outcome Study Short Form 36-Item Health Survey (SF-36), Version 2 at Week 16 and 24

  • Quality of Life Questionnaire: Dermatology Life Quality Index (DLQI) at Week 16 and 24 [ Time Frame: Baseline to week 16 and 24 ] [ Designated as safety issue: No ]
    Change from baseline in reference to the QOL instrument: Dermatology Life Quality Index (DLQI) at Week 16 and 24

  • Time to relapse (50% loss of maximal improvement in subjects who achieved > PASI-50 during the treatment phase) during the observational follow-up phase [ Time Frame: From end of treatment to throughout the duration of the follow-up phase ] [ Designated as safety issue: No ]
    50% loss of maximal improvement during the observational follow-up phase in subjects who achieved > PASI-50 during the treatment phase from end of treatment throughout the follow-up

  • Area under the plasma concentration-time curve (AUC0-8) [ Time Frame: From baseline to week 16 and week 24 ] [ Designated as safety issue: No ]
    Systemic exposure of apremilast at Weeks 16 and 24 in reference to the Area under the plasma concentration-time curve (AUC0-8)

  • Peak (maximum) plasma concentration of drug (Cmax) [ Time Frame: From baseline to week 16 and week 24 ] [ Designated as safety issue: No ]
    Systemic exposure of apremilast at Weeks 16 and 24 in reference to the peak (maximum) plasma concentration of drug (Cmax)

  • Time to maximum plasma concentration of drug (tmax) [ Time Frame: From baseline to week 16 and week 24 ] [ Designated as safety issue: No ]
    Systemic exposure of apremilast at Weeks 16 and 24, in reference to the time to maximum plasma concentration of drug (tmax)


Enrollment: 352
Study Start Date: September 2008
Study Completion Date: October 2009
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Apremilast 10mg
Apremilast 10 mg administered orally twice daily (BID) for 16 weeks (following dose titration) during the placebo controlled phase followed by 10 mg Apremilast tablets orally administered BID for 8 weeks in the active treatment phase
Drug: Apremilast 10mg
Other Names:
  • Apremilast tablets
  • CC-10004
  • Otezla
Experimental: Apremilast 20mg
Apremilast 20 mg administered orally twice daily (BID) for 16 weeks (following dose titration) during the placebo controlled phase followed by 20 mg Apremilast tablets orally administered BID for 8 weeks in the active treatment phase
Drug: Apremilast 20mg
Other Names:
  • Apremilast tablets
  • CC-10004
  • Otezla
Experimental: Apremilast 30 mg
Apremilast 30 mg administered orally twice daily (BID) for 16 weeks (following dose titration) during the placebo controlled phase followed by 30 mg Apremilast tablets orally administered BID for 8 weeks in the active treatment phase
Drug: Apremilast 30 mg
Other Names:
  • Apremilast tablets
  • CC-10004
  • Otezla
Placebo Comparator: Placebo
Oral Placebo tablets administered twice daily (BID) for 16 weeks during the placebo-controlled phase.
Drug: Placebo
Experimental: Placebo/Apremilast 20 mg
Participants initially randomized to receive placebo twice daily during the 16 week placebo controlled phase are re-randomized to 20 mg apremilast BID during the 8 week active treatment phase
Drug: Apremilast 20mg
Other Names:
  • Apremilast tablets
  • CC-10004
  • Otezla
Experimental: Placebo/Apremilast 30mg
Participants initially randomized to receive placebo twice daily during the 16 week placebo controlled phase are re-randomized to 30 mg apremilast BID during the 8 week active treatment phase
Drug: Apremilast 30mg
Other Names:
  • Apremilast tablets
  • CC-10004
  • Otezla

Detailed Description:

This study will fully explore the extent of treatment benefit achieved with doses up to 30 mg PO BID and with treatment duration for up to 6 months. In addition, it is important to determine the minimally effective dose for apremilast and more fully elucidate the dose response curve in this patient population. The results from this study will guide the selection of the dose to be tested in the phase 3 trials.

Participants meeting eligibility criteria at the Baseline Visit (Week 0) will be centrally randomized with the use of a permuted-block randomization list, with equal allocation to each of the four treatment arms: 10 mg, 20 mg or 30 mg PO BID of apremilast or placebo. In an effort to mitigate the dose-dependent adverse effects of apremilast (e.g., headache or gastrointestinal disturbances), participants will have their dose titrated over a 7-day period (Study Days 1 -7). Participants will take 10 mg PO BID of apremilast or identically-appearing placebo during Days 1 to 2. Participants randomized to the 10 mg BID dose will continue taking this dose throughout the treatment phase of the study. Those participants randomized to the 20 mg BID dose will dose titrate to 20 mg PO BID of apremilast or identically-appearing placebo during Days 3 to 4 of dosing. Participants randomized to the 20 mg BID dose will continue taking this dose throughout the treatment phase of the study. Those participants randomized to the 30 mg BID dose will dose titrate to 30 mg PO BID of apremilast or identically-appearing placebo during Days 5 to 7 and continue taking this dose throughout the treatment phase of the study. At Week 16, all participants originally randomized to the placebo arm will be re-randomized to receive 20 mg BID or 30 mg BID of apremilast. All participants (i.e., those that are continuing their Apremilast dosing regimen, as well as those newly switching from placebo to apremilast) will receive drug at Week 16 in a treatment arm blinded fashion. In addition, participants transitioning from placebo to active medications at Week 16 will complete a dose titration to mitigate any potential GI side effects that might jeopardize the blinding of the treatment arms.

  Eligibility

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

Inclusion Criteria:

  • Understand and voluntarily sign an informed consent form
  • ≥18 years of age at the time of signing the informed consent form
  • Able to adhere to the study visit schedule and other protocol requirements.
  • Diagnosis of chronic, stable plaque psoriasis at least 6 months prior to screening as defined by:

    1. PASI score ≥ 12
    2. BSA ≥ 10%
  • Candidate for photo/systemic therapy
  • In good health as judged by the investigator, based on medical history, physical examination, 12-lead ECG, serum chemistry, hematology, immunology, and urinalysis
  • Meet all laboratory criteria as defined per
  • Females of childbearing potential (FCBP) must have a negative urine pregnancy test at screening (Visit 1). In addition, sexually active FCBP must agree to use TWO of the following adequate forms of contraception methods. A FCBP must agree to have pregnancy tests every 4 weeks while on study medication
  • Males (including those who have had a vasectomy) must agree to use barrier contraception (latex condoms) when engaging in reproductive sexual activity with FCBP while on study medication and for 84 days after taking the last dose of study medication

Exclusion Criteria:

  • History of clinically significant disease(as determined by the investigator)
  • Pregnant or breastfeeding
  • History of active mycobacterial infection within 3 years
  • History of Human Immunodeficiency Virus (HIV) infection
  • Congenital and acquired immunodeficiencies
  • Hepatitis B surface antigen positive or Hepatitis B core antibody positive at screening
  • Antibodies to Hepatitis C at screening
  • Malignancy or history of malignancy except for treated [i.e., cured] basal-cell skin carcinomas
  • 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
  • Psoriasis flare within 4 weeks of screening
  • Topical therapy within 2 weeks of randomization
  • Systemic therapy for psoriasis within 4 weeks of randomization
  • Use of phototherapy within 4 weeks of randomization (i.e., UVB, PUVA)
  • Adalimumab, etanercept, efalizumab or infliximab within 12 weeks of randomization
  • Alefacept within 24 weeks of randomization
  • Investigational drug within 4 weeks of randomization, or 5 pharmacokinetic/pharmacodynamic half lives, if known (whichever is longer)
  • Prolonged sun exposure or use of tanning booths or other ultraviolet light sources
  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: NCT00773734

  Show 35 Study Locations
Sponsors and Collaborators
Celgene Corporation
Investigators
Study Director: Irina Khanskaya, MD Celgene Corporation
  More Information

No publications provided by Celgene Corporation

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Celgene Corporation
ClinicalTrials.gov Identifier: NCT00773734     History of Changes
Other Study ID Numbers: CC-10004-PSOR-005
Study First Received: October 14, 2008
Last Updated: May 6, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

Keywords provided by Celgene Corporation:
moderate-to-severe plaque-type psoriasis

Additional relevant MeSH terms:
Psoriasis
Skin Diseases, Papulosquamous
Skin Diseases
Apremilast
Thalidomide
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
Immunosuppressive Agents
Immunologic Factors
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents

ClinicalTrials.gov processed this record on September 22, 2014