Apremilast Safety and PK Study in Recalcitrant Plaque Psoriasis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT00521339
First received: August 24, 2007
Last updated: April 11, 2014
Last verified: August 2013
  Purpose

The study will test the safety and tolerability of CC-10004 twice a day in participants with recalcitrant plaque type psoriasis.


Condition Intervention Phase
Psoriasis-Type Psoriasis
Drug: Apremilast; CC-10004
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2, Open-label Multi-center Study to Evaluate the Safety, Pharmacodynamics, Pharmacokinetics, and Efficacy of Apremilast in Subjects With Recalcitrant Plaque-type Psoriasis

Resource links provided by NLM:


Further study details as provided by Celgene Corporation:

Primary Outcome Measures:
  • Safety and Tolerability [ Time Frame: Up to 6 months ] [ Designated as safety issue: Yes ]
    Evaluate the clinical safety of up to 6 months of therapy with 20 mg Apremilast orally twice daily in participants with plaque type posoriasis. Adverse events will be classified using the Medical Dictionary for Drug Regulatory Activities (MedDRA) classification system. All AEs, as well as treatment emergent AEs, will be summarized by system organ class, preferred term, severity, and relationship to study medication. Tolerability will be assessed by summarizing the number of participants who prematurely withdraw from the study due to intolerance of overt adverse effects of study medication and/or dose reductions.


Secondary Outcome Measures:
  • Change in peripheral blood T cell, B cell, and NK cell subsets [ Time Frame: From baseline to Day 85 ] [ Designated as safety issue: No ]
    Absolute and percent change in peripheral T, B and NK cells at Day 85

  • Change in epidermal thickness and change in inflammatory markers in psoriatic skin biopsies [ Time Frame: From baseline to Day 85 ] [ Designated as safety issue: No ]
    Absolute and percent change in epidermal thickness and change in inflammatory markers in psoriatic skin biopsies

  • Area under the plasma concentration time-curve (AUC) [ Time Frame: Day 1 pre-dose and 12 hours after AM dose; Days 8, 15, 29, 43 and 57, 71, Day 85 and for those who dose escalate, Day 169. ] [ Designated as safety issue: No ]
    Area under the plasma concentration time-curve (AUC) of CC-10004, calculated by the linear trapezoidal rule

  • Peak (maximum) plasma concentration of medication (Cmax) [ Time Frame: Day 1 pre-dose and 12 hours after AM dose; Days 8, 15, 29, 43 and 57, 71, Day 85 and for those who dose escalate, Day 169. ] [ Designated as safety issue: No ]
    The maximum observed plasma concentration of CC-10004 (Cmax)

  • Trough Plasma Concentration (tmax) [ Time Frame: Day 85 and 169 ] [ Designated as safety issue: No ]
    The trough observed plasma concentration of CC-10004 (tmax)

  • Time to maximum plasma concentration (tmax) [ Time Frame: Day 1 pre-dose and 12 hours after AM dose; Days 8, 15, 29, 43 and 57, 71, Day 85 and for those who dose escalate, Day 169. ] [ Designated as safety issue: No ]
    The time to the first maximum observed plasma concentration of CC-10004 (tmax)

  • Terminal phase elimination half life of cc-10004 (t½) [ Time Frame: Day 1 pre-dose and 12 hours after AM dose; Days 8, 15, 29, 43 and 57, 71, Day 85 and for those who dose escalate, Day 169. ] [ Designated as safety issue: No ]
    The terminal half life of cc-10004 (tmax)

  • Apparent total clearance of cc-10004 from plasma after extravascular administration (CL/F) [ Time Frame: Day 1 pre-dose and 12 hours after AM dose; Days 8, 15, 29, 43 and 57, 71, Day 85 and for those who dose escalate, Day 169. ] [ Designated as safety issue: No ]
    The apparent total clearance of cc-10004 from plasma after extravascular administration (CL/F)

  • Apparent total volume of distribution during the terminal phase after extravascular administration (Vz/F) [ Time Frame: Day 1 pre-dose and 12 hours after AM dose; Days 8, 15, 29, 43 and 57, 71, Day 85 and for those who dose escalate, Day 169. ] [ Designated as safety issue: No ]
    The apparent total volume of distribution during the terminal phase after extravascular administration (Vz/F)

  • Accumulation Index (R) [ Time Frame: Day 1 pre-dose and 12 hours after AM dose; Days 8, 15, 29, 43 and 57, 71, Day 85 and for those who dose escalate, Day 169. ] [ Designated as safety issue: No ]
    Accumulation represents the relationship between the dosing interval and the rate of elimination for the drug.

  • Mean Residence Time (MRT) [ Time Frame: Day 1 pre-dose and 12 hours after AM dose; Days 8, 15, 29, 43 and 57, 71, Day 85 and for those who dose escalate, Day 169. ] [ Designated as safety issue: No ]
    Mean duration of time the drug spends in the body.

  • Shift change (1 or more points reduction on 0 to 5 point scale) in static Physician Global Assessment (sPGA) [ Time Frame: From baseline to Day 85 and Day 169 ] [ Designated as safety issue: No ]
    Proportion of participants with a Static Physician's Global Assessment (sPGA) of overall disease severity score of clear (0) or almost clear (1) with at least 2 points reduction from baseline

  • Change in Psoriasis Area Severity Index (PASI) score [ Time Frame: From baseline (Day 1) to Day 85 and Day 169 ] [ Designated as safety issue: No ]
    Change in the PASI score at Day 85 and at Day 169. The lesions on each area of the body will be assessed for redness, thickness, and scaling.

  • Proportion of participants treated with CC-10004 who achieve a PASI-75 score [ Time Frame: From Baseline (Day1) to Day 85 and 169 ] [ Designated as safety issue: No ]
    Proportion of participants who achieve PASI-75 (at least a 75% reduction from baseline). The lesions on each area of the body will be assessed for redness, thickness, and scaling.

  • Proportion of participants who achieve a PASI-50 score [ Time Frame: From Baseline (Day 1) to Day 85 and 169 ] [ Designated as safety issue: No ]
    Proportion of participants who achieve PASI-50 (at least a 50% reduction from baseline). The lesions on each area of the body will be assessed for redness, thickness, and scaling.

  • Maximal PASI response documented for each participant during treatment and extension phase. [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]
    The lesions on each area of the body will be assessed for redness, thickness, and scaling.

  • Change in Body Surface Area (BSA) affected [ Time Frame: From Baseline (Day 1) to Day 85 and Day 169 ] [ Designated as safety issue: No ]
    Percent change from baseline in the body surface area (BSA) affected by psoriasis.

  • Time to clinically relevant response (time to achieve PASI-50) during treatment and extension phase [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]
    The duration of treatment needed for a participant to achieve a 50% improvement in their PASI score. The lesions on each area of the body will be assessed for redness, thickness, and scaling.

  • Time to achieve PASI-75 during treatment and extension phase [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]
    The duration of treatment needed for a subject to achieve a 75% improvement in their PASI score. The lesion on each area of the body will be assessed for redness, thickness, and scaling.

  • Time to relapse of psoriasis during the observational phase [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]
    50% loss of maximal PASI score improvement in participants who achieved at least PASI-50 during the treatment or extension phase. The lesion on each area of the body will be assessed for redness, thickness, and scaling.

  • Proportion of participants with psoriatic arthritis who achieve the American College of Rheumatology (ACR) criteria for 20% improvement (ACR 20) [ Time Frame: From Baseline (Day 1) to Day 85 and Day 169 ] [ Designated as safety issue: No ]
    Proportion of participants who achieve ACR-20 (at least a 20% reduction from baseline).

  • Time to relapse of psoriatic arthritis during the observational follow-up phase [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]
    50% loss of maximal ACR score improvement in participants with psoriatic arthritis who achieved at least ACR 20 during the treatment or extension phase.

  • Change in Dermatology Life Quality Index (DLQI) and Medical Outcome Study Short Form 36-item Health Survey (SF-36), Version 2 [ Time Frame: From Baseline (Day 1) to Day 85 and 169 ] [ Designated as safety issue: No ]
    Change from baseline in the DLQI and SF-36 scores.


Enrollment: 31
Study Start Date: August 2007
Study Completion Date: May 2009
Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Apremilast 20 mg BID/ 30 mg BID
Apremilast 20 mg or 30 mg orally twice per day
Drug: Apremilast; CC-10004
20 mg PO (by mouth) twice per day (BID) for 84 days and then an additional 84 days during the optional treatment extension period. For subjects meeting the dose escalation criteria, dosage during the optional treatment extension period can be increased to 30 mg BID.
Other Names:
  • Apremilast
  • CC-10004

Detailed Description:

This is a phase 2, multicenter, open-label, study to evaluate the safety, tolerability, pharmacodynamics, pharmacokinetics and efficacy of CC-10004 in participants with recalcitrant plaque-type psoriasis.

Approximately 20 participants will be enrolled and receive 20 mg and, in subject who are non-responders after 84 days of treatment, 30 mg of CC-10004 over the course of the two study treatment phases. The study will consist of four phases: Screening Phase - up to 35 days, Treatment Phase of 84 days, Extension Phase of 84 days and a Follow-up Phase of 28 days.

During the Treatment Phase, participants will take two 20 mg CC-10004 capsules each day. Following the Treatment Phase, participants will have the option to continue on treatment during the Extension Phase. During the Extension Phase, participants will either continue to take two 20 mg or dose escalate to two 30 mg of CC-10004 each day. Participants who are considered responders (achieve a PASI-75) at the beginning of the Extension Phase will stay on 20 mg twice per day while the remaining participants will receive 30 mg capsules twice per day. All participants will be asked to participate in a 4-week post-treatment observational follow-up phase either upon completion of the study or upon discontinuation of study drug for those participants who terminate the study early.

  Eligibility

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

Inclusion Criteria:

Must understand and voluntarily sign an informed consent form

  • Must be male or female subject of any ethnic origin or race that is >18 years at time of consent
  • Must have a documented history of plaque-type psoriasis for at least 6 months prior to screening visit
  • Subjects must fulfill criteria outlined in at least one of the following clinical categories:

    • Unresponsive to standard systemic therapy, as defined by clinical history, in the investigator's opinion, i.e. inadequate response to one or more adequate treatment course (s) of standard systemic therapy
    • Intolerant to or cannot receive (e.g., contraindication to prescribe) standard systemic therapy or biological interventions for psoriasis
  • Must have a sPGA score of at least 3 and a BSA ≥ 10% at screening
  • Must meet the specified laboratory criteria:

Must be able to adhere to the study visit schedule and study protocol requirements

  • Females of childbearing potential (FCBP)[1] must have a negative urine pregnancy test at screening (Visit 1). In addition, FCBP must agree to use two of the following adequate forms of contraception methods such as oral, injectable, or implantable hormonal contraception; tubal ligation; intrauterine device; barrier contraceptive with spermicide or vasectomized partner while on study. 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 sexual activity with FCBP

Exclusion Criteria:

History of clinically significant (as determined by the investigator) cardiac, endocrinologic, pulmonary, neurologic, psychiatric, hepatic, renal, hematologic, immunologic, or other major disease

  • 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
  • Pregnant or lactating females
  • History of active tuberculosis (TB)infection within 3 years prior to the screening visit. Infections which occurred > 3 years prior to entry must have been effectively treated
  • History of incompletely treated latent (as indicated by a positive PPD [purified protein derivative] skin results) TB infection
  • Clinically significant abnormality on the chest x-ray (CXR) at screening
  • Psoriasis flare within 30 days of screening, as defined by protocol
  • Use of systemic therapy for psoriasis within 28 days of Visit 2 (Baseline).
  • Topical therapy as defined in the protocol Adalimumab, etanercept, efalizumab or infliximab use within 56 days of Visit 2 (Baseline)
  • Alefacept use within 180 days of Visit 2 (Baseline)
  • Phototherapy (UVA, NB-UVB, PUVA) within 28 days of Visit 2 (Baseline)
  • Use of any investigational drug within 28 days of Visit 2 (Baseline), or 5 half lives if known (whichever is longer)Clinically significant abnormality on 12-lead ECG at screening
  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: NCT00521339

Locations
United States, Massachusetts
Tufts-New England Medical Center Hospitals
Boston, Massachusetts, United States, 02111
United States, Missouri
Central Dermatology
St. Louis, Missouri, United States, 63117
United States, Oregon
Oregon Medical Research Center, P.C.
Portland, Oregon, United States, 97223
United States, Texas
Baylor Research Institute
Dallas, Texas, United States, 75246-1613
Sponsors and Collaborators
Celgene Corporation
Investigators
Study Director: Robert Day, PhD 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: NCT00521339     History of Changes
Other Study ID Numbers: CC-10004-PSOR-004
Study First Received: August 24, 2007
Last Updated: April 11, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Celgene Corporation:
Apremilast,
Psoriasis,
PASI-75,
sPGA

Additional relevant MeSH terms:
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 July 22, 2014