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: August 21, 2015
Last verified: August 2015
  Purpose

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.

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.


Condition Intervention Phase
Psoriasis
Psoriatic Arthritis
Drug: Apremilast tablet/pill 30 mg
Drug: Etanercept 50 mg
Drug: Placebo tablet
Drug: Placebo injection (saline)
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 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

Resource links provided by NLM:


Further study details as provided by Celgene Corporation:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • 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 From Baseline [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]
    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 ] [ 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%) for Comparison Between Apremilast and Placebo and Etanercept and Placebo at Week 16 [ Time Frame: Baseline to Week 16 ] [ Designated as safety issue: No ]
    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 (Visit 2 Week 0) was determined at each visit of the study, which is calculated as 100*(visit 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: From Baseline to Week 16 ] [ Designated as safety issue: No ]
    A participant was classified as having at least a 50% improvement in PASI score from baseline, which was equivalent to a percent change from baseline ranging from −100% to −50%. PASI score is based on an assessment of erythema (reddening), induration (plaque thickness), desquamation (scaling), and the percent area affected as observed on the day of examination.

  • Change From Baseline in Dermatology Life Quality Index (DLQI) In Comparison Between Apremilast and Placebo and Etanercept and Placebo at Week 16 [ Time Frame: Baseline to Week 16 ] [ Designated as safety issue: No ]
    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 and Week 16 ] [ Designated as safety issue: No ]

    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. Two overall summary scores were obtained − a Physical Component Summary score (PCS) and a Mental Component Summary score (MCS).

    Scores from the 8 scales, PCS and MCS were transformed to the norm-based scores using weights from U.S. general population, with higher scores indicating better health. For norm based scores, change from baseline were calculated for the 8 scales and the two summary scales, where change = visit value − baseline value.


  • Percentage of Participants With 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 ] [ 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 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: First dose of study drug to the end of the placebo controlled phase ] [ Designated as safety issue: Yes ]
    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 those 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 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: First dose of study drug to the end of the placebo controlled phase ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 250
Study Start Date: October 2012
Estimated Study Completion Date: April 2016
Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Apremilast 30 mg plus placebo injection Drug: Apremilast tablet/pill 30 mg
Apremilast tablet/pill 30 mg tablet orally twice a day
Other Name: CC-10004
Drug: Placebo injection (saline)
once weekly evaluator/subject-blinded subcutaneous saline (placebo) injections (1 mL x 2 injections SC)
Other Name: Placebo
Experimental: Etanercept 50 mg plus placebo tablet 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
Placebo Comparator: Placebo 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

Detailed Description:

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.

  Eligibility

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

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.
  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: NCT01690299

  Show 82 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: NCT01690299     History of Changes
Other Study ID Numbers: CC-10004-PSOR-010, 2012-000859-14
Study First Received: September 19, 2012
Results First Received: July 2, 2015
Last Updated: August 21, 2015
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Australia: Department of Health and Ageing Therapeutic Goods Administration
Belgium: Federal Agency for Medicinal Products and Health Products
Germany: Federal Institute for Drugs and Medical Devices
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Celgene Corporation:
Psoriasis
arthritis
psoriatic
psoriasis
palmoplantar
scalp
psoriasis pill
psoriasis tablet
plaque psoriasis
plaque type psoriasis
moderate to severe plaque type psoriasis
psoriatic arthritis

Additional relevant MeSH terms:
Arthritis, Psoriatic
Psoriasis
Arthritis
Bone Diseases
Joint Diseases
Musculoskeletal Diseases
Skin Diseases
Skin Diseases, Papulosquamous
Spinal Diseases
Spondylarthritis
Spondylarthropathies
Spondylitis
Apremilast
TNFR-Fc fusion protein
Analgesics
Analgesics, Non-Narcotic
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Antirheumatic Agents
Central Nervous System Agents
Enzyme Inhibitors
Gastrointestinal Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Peripheral Nervous System Agents
Pharmacologic Actions
Phosphodiesterase Inhibitors
Physiological Effects of Drugs
Sensory System Agents

ClinicalTrials.gov processed this record on September 02, 2015