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

Study Overview
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Brief Summary
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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.

Detailed Description
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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 participants with moderate to severe plaque psoriasis.

Official Title
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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

Conditions
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Psoriasis, Psoriatic Arthritis, Psoriasis Arthropatica

Intervention / Treatment
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* Drug: Apremilast
* Drug: Apremilast
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female Japanese participants 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: Psoriasis Area Severity Index (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 electrocardiogram (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 participant 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 or carcinoma in situ (CIN) 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: Ultraviolet light B (UVB), Psoralens and long-wave ultraviolet radiation (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.

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Apremilast 20mg<br>Apremilast 20 mg tablets orally twice a day (BID) | Drug: Apremilast<br>* 20 mg tablet BID for 68 weeks<br>* Other names: Otzela;Drug: Placebo<br>* Placebo tablet BID for 16 weeks<br>|
| Experimental: Apremilast 30mg<br>Apremilast 30 mg tablets orally BID | Drug: Apremilast<br>* 20 mg tablet BID for 68 weeks<br>* Other names: Otzela;Drug: Placebo<br>* Placebo tablet BID for 16 weeks<br>|
| Placebo Comparator: Placebo<br>Identically-appearing placebo tablets BID for 16 weeks followed by participants being re-randomized in a blinded fasion to apremilast 20 mg or 30mg tablets BID for 52 weeks | Drug: Placebo<br>* Placebo tablet BID for 16 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Achieved a 75% Improvement (Response) From Baseline in the Psoriasis Area and Severity Index (PASI-75) at 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. | Baseline to Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Achieved a Static Physician's Global Assessment (sPGA) Score of Clear (0) or Almost Clear (1) With at Least 2 Point Reduction From Baseline to Week 16 | The sPGA is a measure of psoriasis disease severity at the time of evaluation by the Investigator. It does not compare assessments across visits or rely on investigator recall or prior disease. 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 participant 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. | Baseline to Week 16 | 
| Percent Change From Baseline in the Psoriasis Affected Body Surface Area (BSA) at Week 16 | 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. | Baseline to Week 16 | 
| Percent Change From Baseline in the Psoriasis Area and Severity Index (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. The PASI scores range from 0 to 72, with higher scores reflecting a greater disease severity. | Baseline to Week 16 | 
| Percentage of Participants Who Achieved a 50% Improvement From Baseline (Response) Reduction in the PASI-50 at 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 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 is missing. | Baseline to Week 16 | 
| Change From Baseline in Pruritus Visual Analogue Scale 100-mm (VAS) at Week 16 | The pruritus visual analog scale (VAS) was used to measure the amount of itching and discomfort a participant experiences. Participant's assessment of pruritus (Itch) asked: On average, how much itch have you had because of your condition in the past week? Higher scores correspond to more severe symptom or disease. The participant 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. VAS scores range from 0 to 100 mm, where higher scores correspond to worse pruritis (itch). | Baseline to Week 16 | 
| Change From Baseline in the Dermatology Life Quality Index (DLQI) Total Score at Week 16 | 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 participants 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 has a possible range from 0 to 30, with 30 corresponding to the worst quality of life, and 0 corresponding to the best. | Baseline to Week 16 | 
| Change From Baseline in Mental Component Summary (MCS) Score of the Medical Outcome Study Short Form 36-item (SF-36) Health Survey Version 2.0 at Week 16 | 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 quality of life (better functioning) | Baseline to Week 16 | 
| Number of Participants Who Achieved an American College of Rheumatology Criteria (ACR) 20% Improvement (ACR 20) | 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. | Baseline to Week 16 | 
| Percent Change From Baseline Psoriatic Arthritis Pain Visual Analogue Scale (VAS) | Change from baseline in psoriatic arthritis pain 100-mm VAS; The participant 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. | Baseline to Week 16 | 
| Percent Change From Baseline in Physical Function Assessment Using the Health Assessment Questionnaire Disability Index (HAQ-DI) | 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. | Baseline to Week 16 | 
| Number of Participants With Adverse Events (AE) in the Placebo Controlled Phase | An AE was any noxious, unintended, or untoward medical occurrence, that may appear or worsen in a participant during the course of study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant'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) was considered an AE. A serious AE (SAE) is any untoward adverse event that is fatal, life-threatening, results in persistent or significant disability or incapacity, requires or prolongs existing in-patient hospitalization, is a congenital anomaly or birth defect, or a condition that may jeopardize the patient or may require intervention to prevent one of the outcomes listed above. An AE is a treatment emergent AE if the AE start date is on or after the date of the first dose of study drug and no later than 28 days after the last dose. | Baseline to Week 16 | 
| Number of Participants With Adverse Events (AE) in the During the Apremilast-exposure Period | An AE was any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant'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) was considered an AE. A serious AE (SAE) is any untoward adverse event that is fatal, life-threatening, results in persistent or significant disability or incapacity, requires or prolongs existing in-patient hospitalization, is a congenital anomaly or birth defect, or a condition that may jeopardize the patient or may require intervention to prevent one of the outcomes listed above. An AE is a treatment emergent AE if the AE start date is on or after the date of the first dose of study drug and no later than 28 days after the last dose. | From the first dose of apremilast (either Week 0 or Week 16 for participants originally randomized to placebo who were re-randomized at Week 16) until 28 days after the last dose of apremilast. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Psoriasis; Psoriatic Arthritis