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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01690299
First Posted: September 21, 2012
Last Update Posted: June 8, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Celgene
September 19, 2012
September 21, 2012
July 2, 2015
August 4, 2015
June 8, 2017
October 1, 2012
July 3, 2014   (Final data collection date for primary outcome measure)
Percentage of Participants Who Achieved a 75% Improvement (Response) in the Psoriasis Area Severity Index (PASI-75) for the Comparison Between Apremilast and Placebo at Week 16 From Baseline [ Time Frame: Baseline to Week 16 ]
PASI-75 response is the percentage of participants who achieved at least a 75% reduction (improvement) from baseline in PASI score at Week 16. The improvement in PASI score was used as a measure of efficacy. The PASI was 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. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The PASI score was set to missing if any severity score or degree of involvement was missing.
Apremilast Psoriasis Area and Severity Index-75 (PASI) [ Time Frame: Week 16 ]
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
  • Percentage of Participants Who Achieved a 75% Improvement (Response) in the Psoriasis Area and Severity Index (PASI) for the Comparison Between Etanercept 50mg SC QW and Placebo at Week 16 [ Time Frame: Baseline and Week 16 ]
    PASI-75 response is the percentage of participants who achieved at least a 75% reduction (improvement) from baseline in PASI score at Week 16. The improvement in PASI score was used as a measure of efficacy. The PASI was 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. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The PASI score was set to missing if any severity score or degree of involvement was missing.
  • Percentage of Participants Who Achieved a Static Physician Global Assessment (sPGA) Score of Clear (0) or Almost Clear (1) With at Least 2 Points Reduction for Comparison Between Apremilast and Placebo and Etanercept and Placebo at Week 16 [ Time Frame: Baseline and Week 16 ]
    The sPGA is an 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) for Comparison Between Apremilast and Placebo and Etanercept and Placebo at Week 16 [ Time Frame: Baseline to Week 16 ]
    BSA is a measurement of involved skin. The overall BSA affected by psoriasis was estimated based on the palm area of the participant's hand (entire palmar surface or "handprint" including the fingers), which equates to approximately 1% of total body surface area. BSA percent change from baseline was determined at each visit of the study, and is calculated as 100*(post-baseline BSA - baseline BSA) / baseline BSA.
  • Percentage of Participants Who Achieved a 50% Improvement (Response) in the Psoriasis Area Severity Index (PASI-50) for Comparison Between Apremilast and Placebo and Etanercept and Placebo at Week 16 [ Time Frame: Baseline to Week 16 ]
    PASI-50 response is the percentage of participants who achieved at least a 50% reduction (improvement) from baseline in PASI score at Week 16. The PASI score was 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. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The PASI score was set to missing if any severity score or degree of involvement was missing.
  • Change From Baseline in Dermatology Life Quality Index (DLQI) Total Score In Comparison Between Apremilast and Placebo and Etanercept and Placebo at Week 16 [ Time Frame: Baseline to Week 16 ]
    DLQI is a simple, compact, and practical questionnaire for use in a dermatology clinical setting to assess limitations related to the impact of skin disease. The instrument contains ten items dealing with the participant's skin. With the exception of Item Number 7, the participant responds on a four-point scale, ranging from "Very Much" (score 3) to "Not at All" or "Not relevant" (score 0). Item Number 7 is a multi-part item, the first part of which ascertains whether the participant's skin prevented them from working or studying (Yes or No, scores 3 or 0 respectively), and if "No," then the participant is asked how much of a problem the skin has been at work or study over the past week, with response alternatives being "A lot," "A little," or "Not at all" (scores 2, 1, or 0 respectively). The DLQI total score is derived by summing all item scores, which has a possible range of 0 to 30, with 30 corresponding to the worst quality of life, and 0 corresponding to the best.
  • Change From Baseline in the Mental Component Summary (MCS) Score of the Medical Outcome Study Short Form 36-item (SF-36) Health Survey Version 2.0 in Comparison Between Apremilast and Placebo and Etanercept and Placebo at Week 16 [ Time Frame: Baseline to Week 16 ]
    The SF-36 is a 36-item general health status instrument and 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). Scale scores range from 0 to 100, with higher scores indicating better health. Scores from the 8 scales were transformed to the norm-based scores using weights from U.S. general population to have a mean of 50 and variance = 10, with higher scores indicating better health. From these 8 scale, two overall summary scores were obtained − a Physical Component Summary score (PCS) and a Mental Component Summary score (MCS), both having the same mean of 50 and variance = 10 as noted for the individual scales for the U.S. general population, and with higher scores indicating better health. For MCS, change from baseline was calculated, where change = visit value − baseline value.
  • Percentage of Participants Who Achieved a Lattice System Physician's Global Assessment (LS-PGA) Score of Clear (0) or Almost Clear at Week 16 in Comparison Between Apremilast and Placebo and Etanercept and Placebo at Week 16 [ Time Frame: Baseline to Week 16 ]
    The Lattice System Physician's Global Assessment is a global assessment performed 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 overall assessment 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 qualities, weights plaque elevation as most important, erythema next, and scale least.
  • Number of Participants With Treatment Emergent Adverse Events (TEAE) During the Placebo-Controlled Phase [ Time Frame: Week 0 to Week 16; mean duration of exposure was 14.90 weeks for placebo group, 15.13 weeks for apremilast group and 15.87 weeks for Etanercept group ]
    A TEAE is an AE with a start date on or after the date of the first dose of study drug and no later than 28 days after the last dose of study drug for participants who discontinued early. An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen during the study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the patient's health, including laboratory test values, regardless of etiology. Any worsening (ie, clinically significant adverse change in frequency or intensity of a preexisting condition) should be considered an AE. A serious AE (SAE) is any untoward AE that is fatal, life-threatening, results in persistent or significant disability or incapacity, requires or prolongs existing in-patient hospitalization, is a congenital anomaly/birth defect, or is a condition that may jeopardize or may require intervention to prevent one of the outcomes above.
  • Number of Participants With Treatment Emergent Adverse Events (TEAE) During the Apremilast-exposure Period [ Time Frame: From the first dose of apremilast (either Week 0 for participants originally randomized to apremilast or Week 16 for those originally randomized to placebo or etanercept who were switched to apremilast at week 16) until 28 days after last apremilast dose ]
    A TEAE in the apremilast-exposure phase is an AE with a start date on or after the date of the first dose of study drug and no later than 28 days after the last dose of study drug. An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen during the 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, 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. A serious AE (SAE) is any untoward AE that is fatal, life-threatening, results in persistent or significant disability or incapacity, requires or prolongs existing in-patient hospitalization, is a congenital anomaly/birth defect, or is a condition that may jeopardize or may require intervention to prevent one of the outcomes listed above.
  • Psoriasis Flare/Rebound [ Time Frame: Week 0 to Week 16; Placebo controlled phase ]
    Psoriasis flare is an 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 more inflammatory psoriasis after stopping therapy.
  • Psoriasis Flare/Rebound [ Time Frame: From the first dose of apremilast (either Week 0 or Week 16 for participants originally randomized to placebo or etanercept who were switched at Week 16) until 28 days after the last dose of apremilast. ]
    Psoriasis flare is an 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 more inflammatory psoriasis after stopping therapy. PASI ≥125% of baseline score at any visit after the last dose date for those who discontinued within the phase.
  • Etanercept Psoriasis Area and Severity Index-75 (PASI) [ Time Frame: Week 16 ]
    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 ]
    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 ]
    Percent change from baseline in the body surface area (BSA) affected by psoriasis
  • Psoriasis Area and Severity Index-50 (PASI) [ Time Frame: Week 16 ]
    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 ]
    Change from baseline in the Dermatology Life Quality Index (DLQI) total score
  • Mental Component Summary (MCS) [ Time Frame: Week 16 ]
    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 ]
    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 ]
    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 compared with placebo as well as etanercept compared with placebo in the same group of patients with moderate to severe plaque 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 adults with moderate to severe plaque psoriasis.

250 participants 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
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Psoriasis
  • Psoriatic Arthritis
  • Drug: Apremilast
    Apremilast 30 mg tablet orally BID
    Other Names:
    • CC-10004
    • Otezla
  • Drug: Etanercept
    Etanercept 50 mg evaluator/subject-blinded SC QW injection
    Other Name: Enbrel
  • Drug: Placebo tablet
    Placebo tablets BID
  • Drug: Placebo injection
    Once weekly evaluator/subject-blinded SC placebo (1 mL x 2 injections SC)
  • Experimental: Apremilast 30 mg plus placebo injection
    Apremilast 30 mg tablets orally twice a day (BID) plus once weekly (QW) evaluator/subject-blinded subcutaneous (SC) saline (placebo) injections
    Interventions:
    • Drug: Apremilast
    • Drug: Placebo injection
  • Experimental: Etanercept 50 mg plus placebo tablet
    Etanercept 50 mg evaluator/subject-blinded SC QW injections plus placebo tablets orally BID
    Interventions:
    • Drug: Etanercept
    • Drug: Placebo tablet
  • Placebo Comparator: Oral placebo tablets plus SC placebo injections
    Identically matching placebo tablets and evaluator/subject-blinded SC injections
    Interventions:
    • Drug: Placebo tablet
    • Drug: Placebo injection
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
250
April 4, 2016
July 3, 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.
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
Australia,   Belgium,   Canada,   Czechia,   Estonia,   Germany,   Hungary,   Latvia,   Netherlands,   United Kingdom,   United States
Czech Republic
 
NCT01690299
CC-10004-PSOR-010
2012-000859-14 ( EudraCT Number )
Yes
Not Provided
Not Provided
Celgene
Celgene
Not Provided
Study Director: Irina Khanskaya, MD Celgene Corporation
Celgene
May 2017

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