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Phase 3b Safety and Efficacy Study of Apremilast to Treat Moderate to Severe Plaque-plaque Psoriasis

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT01690299
First received: September 19, 2012
Last updated: February 24, 2015
Last verified: February 2015

September 19, 2012
February 24, 2015
September 2012
July 2014   (final data collection date for primary outcome measure)
Proportion of subjects with either apremilast BID or placebo who achieve at least a 75% reduction in PASI (PASI-75) at Week 16 from baseline [ Time Frame: Week 16 ] [ Designated as safety issue: No ]
The PASI is a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. The PASI is a validated instrument that has become standard in clinical trials for psoriasis. Higher scores reflect a greater disease severity
Apremilast Psoriasis Area and Severity Index-75 (PASI) [ Time Frame: Week 16 ] [ Designated as safety issue: No ]
Proportion of subjects with either apremilast 30 mg twice a day (BID) or placebo who achieve at least a 75% reduction in PASI (PASI-75) at Week 16 from baseline
Complete list of historical versions of study NCT01690299 on ClinicalTrials.gov Archive Site
  • Proportion of subjects treated with either etanercept or placebo who achieve PASI-75 at Week 16. [ Time Frame: Week 16 ] [ Designated as safety issue: No ]
    The PASI is a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. The PASI is a validated instrument that has become standard in clinical trials for psoriasis. Higher scores reflect a greater disease severity
  • Proportion of subjects with an sPGA score of clear (0) or almost clear (1) with at least 2 points reduction at Week 16 [ Time Frame: Week 16 ] [ Designated as safety issue: No ]
    The sPGA is the assessment by the Investigator of the overall disease severity at the time of evaluation. The sPGA is a 5-point scale ranging from 0 (clear) to 4 (severe), incorporating an assessment of the severity of the three primary signs of the disease: erythema, scaling and plaque elevation. When making the assessment of overall severity, the Investigator should factor in areas that have already been cleared (ie, have scores of 0) and not just evaluate remaining lesions for severity, ie, the severity of each sign is averaged across all areas of involvement, including cleared lesions. In the event of different severities across disease signs, the sign that is the predominant feature of the disease should be used to help determine the sPGA score.
  • Percent change from baseline in the affected body surface area (BSA%) at Week 16 [ Time Frame: Week 16 ] [ Designated as safety issue: No ]
    From Baseline (pre-dose) to Week 16 Description: BSA is a measurement of involved skin. The overall BSA affected by psoriasis is estimated based on the palm area of the subject's hand (entire palmar surface or "handprint" including the fingers), which equates to approximately 1% of total body surface area.
  • Proportion of subjects who achieve a PASI-50 score at Week 16. [ Time Frame: From Baseline (pre-dose) to Week 16 ] [ Designated as safety issue: No ]
    The PASI is a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. The PASI is a validated instrument that has become standard in clinical trials for psoriasis. Higher scores reflect a greater disease severity.
  • Change from baseline in DLQI total score at Week 16 [ Time Frame: From baseline (pre-dose) to Week 16 ] [ Designated as safety issue: No ]
    Dermatology Life Quality Index (DLQI) was developed as a practical questionnaire for use in a dermatology clinical setting to assess limitations related to the impact of skin disease. Higher scores correspond to poorer quality of life.
  • Change from baseline in Mental Component Summary (MCS) score of SF-36 at Week 16 [ Time Frame: Week 16 ] [ Designated as safety issue: No ]
    SF-36 is a 36-item general health status instrument often used in clinical trials and health services research. It consists of 8 scales: physical function (PF), role limitations-physical (RP), vitality (VT), general health perceptions (GH), bodily pain (BP), social function (SF), role limitations-emotional (RE), and mental health (MH) (Ware, 1992). Scale scores range from 0 to 100, with higher scores indicating better health.
  • Proportion of subjects with an LS-PGA score of clear (0) or almost clear (1) at Week 16 [ Time Frame: Week 16 ] [ Designated as safety issue: No ]
    The Lattice System Physician's Global assessment by the investigator of psoriasis severity. Integrating ranges of BSA involvement with assessments of overall plaque severity (using a 4 point scale, from none to marked for the signs of plaque elevation, erythema and scale), the LS-PGA produces an oveall assessement of psoriasis severity on an 8-point scale, ranging from clear to very severe. To determine the final score, the lattice portion is governed by the BSA and among the plaque qualitites, weights plaque elevation as most important, erythema next, and scale least.
  • Adverse Events (AEs): Type, frequency, severity, seriousness and relationship of AEs to IP [ Time Frame: From the time of Informed Consent, through dosing, and for 28 days after the last dose of study medication. Click here to enter text. ] [ Designated as safety issue: Yes ]
    An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the subject's health, including laboratory test values (as specified by the criteria below), regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) should be considered an AE.
  • : Number of subjects who prematurely discontinue IP due to any adverse event [ Time Frame: From Baseline (pre-dose) to Week 16 ] [ Designated as safety issue: Yes ]
    The number of subjects who permanently discontinue treatment and are withdrawn from the study due to the development of an intolerable adverse event, whether related or unrelated to IP.
  • of clinically significant changes in physical examination, vital signs, [ Time Frame: From Baseline (pre-dose) to Week 16 ] [ Designated as safety issue: No ]
    A physical examination included evaluation of skin, nasal cavities, eyes, ears, lymph nodes, and respiratory, cardiovascular, gastrointestinal, neurological, and musculoskeletal systems. Vital signs included assessment of temperature, pulse, seated blood pressure, height, weight, and waist circumference.
  • Psoriasis flare/rebound [ Time Frame: From Baseline (pre-dose) to Week 16 ] [ Designated as safety issue: No ]
    Psoriasis flare is and AE and represents an atypical or unusual worsening of disease during treatment. It is defined as a sudden intensification of psoriasis requiring medical intervention or a diagnosis of new generalized erythrodermic, inflammatory, or pustular psoriasis. Rebound is an AE and is defined as a severe and sudden worsening of disease that occurs after treatment has been discontinued. This exacerbation is characterized by a PASI ≥125% of baseline or a new generalized pustular, erythrodermic, or or more inflammatory psoriasis after stopping therapy.
  • Etanercept Psoriasis Area and Severity Index-75 (PASI) [ Time Frame: Week 16 ] [ Designated as safety issue: No ]
    Proportion of subjects treated with either etanercept 50mg once weekly (QW) or placebo who achieve PASI-75 (at least a 75% reduction in PASI from baseline
  • Disease Severity Score [ Time Frame: Week 16 ] [ Designated as safety issue: No ]
    Proportion of subjects 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
  • Percent change from baseline in the body surface area (BSA) affected by psoriasis [ Time Frame: Week 16 ] [ Designated as safety issue: No ]
    Percent change from baseline in the body surface area (BSA) affected by psoriasis
  • Psoriasis Area and Severity Index-50 (PASI) [ Time Frame: Week 16 ] [ Designated as safety issue: No ]
    Proportion of subjects who achieve PASI-50 (at least a 50% reduction in PASI from baseline)
  • Dermatology Life Quality Index (DLQI) [ Time Frame: Week 16 ] [ Designated as safety issue: No ]
    Change from baseline in the Dermatology Life Quality Index (DLQI) total score
  • Mental Component Summary (MCS) [ Time Frame: Week 16 ] [ Designated as safety issue: No ]
    Change from baseline in the Mental Component Summary (MCS) score of the Medical Outcome Study Short Form 36 - item Health Survey (SF-36)
  • Lattice System Physician's Global Assessment (LS-PGA) [ Time Frame: Week 16 ] [ Designated as safety issue: No ]
    Proportion of subjects with a Lattice System Physician's Global Assessment (LS-PGA) of psoriasis severity score of clear (0) or almost clear (1)
  • Adverse Event [ Time Frame: Week 16 and week 104 ] [ Designated as safety issue: Yes ]
    Number of participants with adverse events
Not Provided
Not Provided
 
Phase 3b Safety and Efficacy Study of Apremilast to Treat Moderate to Severe Plaque-plaque Psoriasis
A Phase 3b, Multicenter, Randomized, Placebo-Controlled, Double Blind, Double-Dummy, Study of the Efficacy and Safety of Apremilast (CC-10004), Etanercept, and Placebo, in Subjects With Moderate to Severe Plaque Psoriasis

This study will test the clinical effectiveness and safety of apremilast, etanercept compared with placebo in the same group of patients with moderate to severe plaque psoriasis.

Apremilast (CC-10004) is a new oral agent that is under clinical development for the treatment of inflammatory autoimmune disorders, such as psoriatic arthritis, psoriasis, rheumatoid arthritis, and Behçet disease.

Etanercept is approved for the treatment of psoriasis; it is the most widely prescribed anti-tumor necrosis factor (TNF) for psoriasis.

This is a phase 3b, multicenter, randomized, placebo-controlled, double-blind, double-dummy, study of the efficacy and safety of apremilast, etanercept, and placebo, in subjects with moderate to severe plaque psoriasis.

Approximately 240 subjects will be randomized 1:1:1 to the three treatment groups. All subjects will receive both tablets and injections through Week 16.

The study will consist of four phases:

  • Screening Phase - up to 35 days
  • Double-blind Placebo-controlled Phase - Weeks 0-16
  • Apremilast Extension Phase - Weeks 16-104
  • Post-treatment Observational Follow-up Phase

During the double-blind, placebo-controlled phase, subjects will receive treatment with one of the following:

  • apremilast (APR) 30 mg tablets orally twice a day (BID) plus once weekly (QW) evaluator/subject-blinded subcutaneous (SC) saline (placebo) injections (1 mL x 2 injections SC), or
  • etanercept (ETN) 50 mg evaluator/subject-blinded subcutaneous (SC) once weekly (QW) injections (2 x 25 mg) plus placebo tablets orally twice a day (BID), or
  • placebo tablets and evaluator/subject-blinded subcutaneous (SC) saline (placebo) injections.

All subjects 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 investigational product for those subjects who terminate the study early.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Psoriasis
  • Psoriatic Arthritis
  • Drug: Apremilast tablet/pill 30 mg
    Apremilast tablet/pill 30 mg tablet orally twice a day
    Other Name: CC-10004
  • Drug: Etanercept 50 mg
    Etanercept 50 mg evaluator/subject-blinded subcutaneous once weekly injection
    Other Name: ETN
  • Drug: Placebo tablet
    Placebo tablets twice a day
    Other Name: Placebo
  • Drug: Placebo injection (saline)
    once weekly evaluator/subject-blinded subcutaneous saline (placebo) injections (1 mL x 2 injections SC)
    Other Name: Placebo
  • Experimental: Apremilast 30 mg plus placebo injection
    Interventions:
    • Drug: Apremilast tablet/pill 30 mg
    • Drug: Placebo injection (saline)
  • Experimental: Etanercept 50 mg plus placebo tablet
    Interventions:
    • Drug: Etanercept 50 mg
    • Drug: Placebo tablet
  • Placebo Comparator: Placebo
    Interventions:
    • Drug: Placebo tablet
    • Drug: Placebo injection (saline)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
250
August 2015
July 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Males or females, ≥ 18 years of age
  • Diagnosis of chronic, moderate to severe plaque psoriasis for at least 12 months prior to Screening, and a candidate for phototherapy and/or systemic (including etanercept) therapy
  • Had an inadequate response, intolerance, or contraindication to at least 1 conventional systemic agent for the treatment of psoriasis.
  • No prior exposure to biologics for treatment of psoriatic arthritis or psoriasis

Exclusion Criteria:

  • Other than psoriasis, history of any clinically significant and uncontrolled systemic diseases; any condition, including the presence of laboratory abnormalities, which would place the subject at unacceptable risk if he/she were to participate in the study.
  • Pregnant or breast feeding.
  • Have failed more than 3 systemic agents for treatment of psoriasis.
  • History of allergy to any component of the investigational product (IP), including human immunoglobulin (Ig) proteins or allergy to etanercept.
  • Hepatitis B surface antigen or anti-hepatitis C antibody positive at Screening.
  • Latent, active tuberculosis (TB) or inadequately treated TB; nontuberculous mycobacterial infection or opportunistic infection (eg, cytomegalovirus, Pneumocystis carinii, aspergillosis, Clostridium difficile).
  • Have a history of, or ongoing, chronic or recurrent infectious disease
  • Have received, or are expected to receive, any live virus or bacterial vaccination within 3 months before first administration of IP, or through Week 20 during the study.
  • Had a Bacillus Calmette-Guérin (BCG) vaccination within 1 year prior to screening.
  • History of positive human immunodeficiency virus (HIV), or have congenital or acquired immunodeficiency (eg, common variable immunodeficiency disease).
  • Active substance abuse or a history of substance abuse within 6 months prior to Screening.
  • Malignancy or history of malignancy, except for treated [ie, cured] basal cell or squamous cell in situ skin carcinomas and cervical intraepithelial neoplasia [CIN] or carcinoma in situ of the cervix with no evidence of recurrence within the previous 5 years.
  • Psoriasis flare or rebound within 4 weeks prior to Screening.
  • Topical therapy within 2 weeks of randomization or systemic therapy for psoriasis within 4 weeks prior to randomization
  • Use of phototherapy within 4 weeks prior to randomization or prolonged sun exposure or use of tanning booths or other ultraviolet (UV) light sources.
  • Any investigational drug within 4 weeks prior to randomization, or 5 pharmacokinetic/pharmacodynamic half lives, if known (whichever is longer).
  • Prior treatment with apremilast or etanercept.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Australia,   Belgium,   Canada,   Czech Republic,   Estonia,   Germany,   Hungary,   Latvia,   Netherlands,   United Kingdom
 
NCT01690299
CC-10004-PSOR-010, 2012-000859-14
Yes
Celgene Corporation
Celgene Corporation
Not Provided
Study Director: Lilia Pineda, MD Celgene Corporation
Celgene Corporation
February 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP