Efficacy and Safety Study of Two Doses of Apremilast (CC-10004) In Japanese Subjects With Moderate-To-Severe Plaque-Type Psoriasis

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT01988103
First received: May 24, 2013
Last updated: September 5, 2014
Last verified: September 2014
  Purpose

This study will test the clinical effectiveness and safety of two orally administered doses of apremilast compared to placebo in Japanese patients with moderate-to-severe plaque-type psoriasis.

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


Condition Intervention Phase
Psoriasis;
Psoriatic Arthritis;
Psoriasis Arthropatica
Drug: Apremilast
Drug: Placebo
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, Efficacy and Safety Study of Two Doses of Apremilast (CC-10004) In Japanese Subjects With Moderate-To-Severe Plaque-Type Psoriasis

Resource links provided by NLM:


Further study details as provided by Celgene Corporation:

Primary Outcome Measures:
  • Psoriasis Area and Severity Index-75 (PASI-75). [ Time Frame: Week 16 ] [ Designated as safety issue: No ]
    Proportion of subjects with either apremilast 20 mg BID, apremilast 30 BID or placebo who achieve at least a 75% reduction from baseline in PASI (PASI-75)


Secondary Outcome Measures:
  • Static Physician's Global Assessment (sPGA) score of clear (0) or almost clear (1) [ Time Frame: Week 16 ] [ Designated as safety issue: No ]
    Proportion of subjects with sPGA scores of clear (0) or almost clear (1); The sPGA is a measure of psoriasis disease severity at the time of evaluation by the Investigator. The sPGA is a 6-point scale ranging from 0 (clear, except for residual discoloration) to 5 (severe; majority of plaques have severe thickness, erythema, and scaling). The investigator examines all of the lesions on the subject and assigns a score ranging from 0 to 5 for thickness, erythema and degree of scaling. Scores for thickness, erythema and scaling are then summed and the mean of these 3 scores equals the overall sPGA score

  • Percent Change from baseline in the psoriasis affected Body Surface Area (BSA %) [ Time Frame: Week 16 ] [ Designated as safety issue: No ]
    Percent Change from baseline in the psoriasis affected BSA (%); 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.

  • Percent Change in the Psoriasis Area and Severity Index (PASI ) score [ Time Frame: From Baseline at Week 16 ] [ Designated as safety issue: No ]
    Percent Change in the PASI score; 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 who achieve PASI-50 [ Time Frame: Week 16 ] [ Designated as safety issue: No ]
    Proportion of subjects who achieve at least a 50% reduction from baseline in PASI score; 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. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity

  • Change from baseline in Pruritus (itch) Visual Analogue Scale (VAS) [ Time Frame: Week 16 ] [ Designated as safety issue: No ]
    Change from baseline in Pruritus 100-mm VAS; The subject places a vertical line on a 100-mm VAS on which the left-hand boundary represents no itch at all and the right-hand boundary represents the worst itch imaginable. The distance from the vertical line to the left-hand boundary is recorded.

  • Change from baseline in Dermatology Life Quality Index (DLQI) total score [ Time Frame: 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. The instrument contains 10 items dealing with the subject's skin. The DLQI Total score has a possible range from 0 to 30, with 30 corresponding to the worst quality of life, and 0 corresponding to the best.

  • Change from baseline in Mental Component Summary (MCS) score of SF-36 [ 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). Scale scores range from 0 to 100, with higher scores indicating better health. Two overall summary scores can also be obtained - a Physical Component Summary score (PCS) and a Mental Component Summary score (MCS).

  • Adverse Events [ Time Frame: Weeks 16 and 68 ] [ Designated as safety issue: Yes ]
    Type, frequency, severity, and relationship of adverse events. An 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 abnormal laboratory test values (which meet certain protocol-specified criteria), regardless of etiology

  • American College of Rheumatology criteria for a 20% improvement (ACR 20) [ Time Frame: Week 16 ] [ Designated as safety issue: No ]
    Proportion of subjects who achieve an ACR 20; For this study, the ACR 20 is defined as a 20% improvement in joint tenderness (78 joint count) and joint swelling scores (76 joint count) compared to baseline plus 20% improvements in 3 of the following 5 assessments (compared to baseline): subject global assessment of disease activity (measured on a 100-mm visual analog scale [VAS]); physician global assessment of disease activity (measured on a 100-mm VAS); subject self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI] score); subject assessment of pain (measured on a 100-mm VAS); and CRP level.

  • Psoriatic Arthritis Pain Visual Analogue Scale (VAS) [ Time Frame: Week 16 ] [ Designated as safety issue: No ]
    Change from baseline in Psoriatic Arthritis Pain 100-mm VAS; The subject places a vertical line on a 100-mm VAS on which the left-hand boundary represents no pain at all and the right-hand boundary represents the worst possible pain. The distance from the vertical line to the left-hand boundary is recorded.

  • Health Assessment Questionnaire Disability Index (HAQ-DI) [ Time Frame: Week 16 ] [ Designated as safety issue: No ]
    Change from baseline in physical function assessment using HAQ-DI; The HAQ-DI is a 20-question, self-administered instrument that measures the subject's functional ability on a 4-level difficulty scale (0-3, with 0 representing normal or no difficulty; and 3 representing inability to perform). Eight categories of functioning are included: dressing, rising, eating, walking, hygiene, reach, grip, and usual activities.

  • Pharmacokinetics - Cmax [ Time Frame: Week 20 ] [ Designated as safety issue: No ]
    Maximum observed concentration in plasma, unit = ng/mL

  • Pharmacokinetics - Tmax [ Time Frame: Week 20 ] [ Designated as safety issue: No ]
    Time of maximum plasma concentration, unit = h

  • Pharmacokinetics - AUC0-8 and AUC0-τ [ Time Frame: Week 20 ] [ Designated as safety issue: No ]
    Area under the concentration-time curve from time 0 to 8 hours and from 0 to 12 hours after a dose of apremilast, unit = ng•h/mL

  • Pharmacokinetics - t1/2 [ Time Frame: Week 20 ] [ Designated as safety issue: No ]
    Elimination half life unit = h

  • Pharmacokinetics - CLss/F [ Time Frame: Week 20 ] [ Designated as safety issue: No ]
    Apparent systemic clearance at steady state, unit = L/h

  • Pharmacokinetics - Vss/F [ Time Frame: Week 20 ] [ Designated as safety issue: No ]
    Apparent volume of distribution at steady state unit = L

  • Population Pharmacokinetics (sparse sampling) - CL/F [ Time Frame: Weeks 8-24 ] [ Designated as safety issue: No ]
    Drug Clearance, unit = L/h

  • Population Pharmacokinetics (sparse sampling) - Vc/F [ Time Frame: Week 8-24 ] [ Designated as safety issue: No ]
    Volume of Distribution, unit = L

  • Population Pharmacokinetics (sparse sampling) - KA [ Time Frame: Week 8-24 ] [ Designated as safety issue: No ]
    Absorption rate constant, unit = 1/h


Enrollment: 254
Study Start Date: May 2013
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Apremilast 20mg Drug: Apremilast
20 mg tablet twice a day for 68 weeks
Experimental: Apremilast 30mg Drug: Apremilast
30 mg tablet twice a day for 68 weeks
Placebo Comparator: Placebo Drug: Placebo
Placebo tablet twice a day for 16 weeks followed by apremilast 20 mg tablet twice a day for 52 weeks
Drug: Placebo
Placebo tablet twice a day for 16 weeks followed by apremilast 30 mg tablet twice a day for 52 weeks

Detailed Description:

This is a phase 2b, multicenter, randomized, double-blind, placebo-controlled study of the efficacy and safety of apremilast 20 mg twice a day (BID), apremilast 30 mg BID, and placebo in Japanese subjects with moderate to severe plaque psoriasis.

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female Japanese subjects greater than or equal to 20 years of age.
  • Diagnosis of chronic, stable plaque psoriasis for at least 6 months prior to screening as defined by: PASI score ≥ 12 and BSA ≥ 10%.
  • Psoriasis which is considered inappropriate for topical therapy (based on severity of disease and extent of affected area) or has not been adequately controlled or treated by topical therapy in spite of at least 4 weeks of prior therapy with at least one topical medication for psoriasis or per label.
  • In otherwise good health based on medical history, physical examination, 12-lead ECG, serum chemistry, hematology, immunology, and urinalysis.

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 or confound the ability to interpret the data in the study.

Prior medical history of suicide attempt or major psychiatric illness requiring hospitalization within the last 3 years

  • Pregnant or breastfeeding.
  • History of or ongoing chronic or recurrent infectious disease.
  • Active tuberculosis (TB) or a history of incompletely treated TB.
  • Clinically significant abnormality on 12-lead ECG or on chest radiograph at screening.
  • History of human immunodeficiency virus (HIV) infection or have congenital or acquired immunodeficiencies (eg, Common Variable Immunodeficiency).
  • Hepatitis B surface antigen or hepatitis B core antibody positive at screening; positive for antibodies to hepatitis C at screening.
  • Malignancy or history of malignancy, except for treated (ie, cured) basal cell or squamous cell in situ skin carcinomas or treated (ie, cured) cervical intraepithelial neoplasia (CIN) or carcinoma in situ of the cervix with no evidence of recurrence within previous 5 years.
  • Psoriasis flare within 4 weeks of screening.
  • Topical therapy within 2 weeks prior to randomization or systemic therapy for psoriasis or psoriatic arthritis within 4 weeks prior to randomization.
  • Use of etretinate within 2 years prior to randomization for females of child bearing potential (FCBP) or within 6 months for males, and within 4 weeks prior to randomization for non-FCBP.
  • Use of phototherapy (ie, UVB, PUVA) within 4 weeks prior to randomization or prolonged sun exposure or use of tanning booths or other ultraviolet light sources.
  • Use of adalimumab, etanercept, certolizumab pegol, abatacept, tocilizumab, golimumab or infliximab within 12 weeks prior to randomization; use of ustekinumab, alefacept or briakinumab within 24 weeks prior to randomization.
  • Any investigational drug within 4 weeks prior to randomization.
  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: NCT01988103

  Show 56 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: NCT01988103     History of Changes
Other Study ID Numbers: CC-10004-PSOR-011
Study First Received: May 24, 2013
Last Updated: September 5, 2014
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency

Keywords provided by Celgene Corporation:
Psoriasis; Psoriatic Arthritis

Additional relevant MeSH terms:
Arthritis
Psoriasis
Arthritis, Psoriatic
Joint Diseases
Musculoskeletal Diseases
Skin Diseases, Papulosquamous
Skin Diseases
Spondylarthropathies
Spondylarthritis
Spondylitis
Spinal Diseases
Bone 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

ClinicalTrials.gov processed this record on September 18, 2014