A Phase 4 Study of Efficacy and Safety of Apremilast in Subjects With Moderate Plaque Psoriasis.

Study Overview
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Brief Summary
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This study will evaluate the clinical efficacy, the patients quality of life, and safety of oral apremilast 30 mg twice daily (BID) compared to placebo, in adult patients with moderate plaque psoriasis during the 16 week Placebo controlled Phase and then upto 1 year in the Extension Phase of the trial.

Detailed Description
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This is a Phase 4, multicenter, randomized, placebo-controlled, double-blind study of the efficacy and safety of apremilast in subjects with moderate plaque psoriasis. 221 participants were randomized 2 (apremilast):1 (placebo) at approximately 25 sites in the United States. Those randomized to the apremilast treatment group received apremilast 30 mg tablets orally twice daily for 52 weeks. Those randomized to the placebo treatment group received placebo tablets (identical in appearance to the apremilast 30 mg tablets) orally twice daily (BID) for 16 weeks. Beginning Week 16, those initially randomized to placebo were switched to receive apremilast 30 mg BID for an additional 36 weeks (52 weeks total). Study enrolled adult patients with stable moderate plaque psoriasis, who are naïve to systemic psoriasis treatments.

Official Title
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A Phase 4, Multicenter, Randomized, Placebo-controlled, Double-blind, Study of the Efficacy and Safety of Apremilast (CC-10004) in Subjects With Moderate Plaque Psoriasis

Conditions
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Parapsoriasis

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females, ≥ 18 years of age at the time of signing the informed consent document. Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures being conducted. Able to adhere to the study visit schedule and other protocol requirements. Diagnosis of chronic plaque psoriasis for at least 6 months prior to signing the informed consent. Have moderate plaque psoriasis at screening and baseline as defined by BSA (Body Surface Area)5% to 10% and sPGA (Physician's Global Assessment) 3 (moderate) based on a 0 to 5 point scale Must be in general good health (except for psoriasis) as judged by the investigator, based on medical history, physical examination, and clinical laboratories. No prior exposure to systemic treatments or biologics for the treatment of psoriatic arthritis, psoriasis, or any other indication that could impact the assessment of psoriasis. Females of childbearing potential (FCBP)must have a negative pregnancy test at Screening and Baseline. While on investigational product and for at least 28 days after taking the last dose of investigational product, FCBP who engage in activity in which conception is possible must use one of the approved contraceptive§ options described below: Option 1: Any one of the following highly effective methods: hormonal contraception (oral, injection, implant, transdermal patch, vaginal ring); intrauterine device (IUD); tubal ligation; or partner's vasectomy; OR Option 2: Male or female condom (latex condom or nonlatex condom NOT made out of natural [animal] membrane [for example, polyurethane]) PLUS one additional barrier method: (a) diaphragm with spermicide; (b) cervical cap with spermicide; or (c) contraceptive sponge with spermicide. Male subjects (including those who have had a vasectomy) who engage in activity in which conception is possible must use barrier contraception (male latex condom or nonlatex condom NOT made out of natural [animal] membrane [for example, polyurethane]) while on investigational product and for at least 28 days after the last dose of investigational product Exclusion Criteria: Other than psoriasis, any clinically significant (as determined by the Investigator) cardiac, endocrinologic, pulmonary, neurologic, psychiatric, hepatic, renal, hematologic,immunologic disease, or other major disease that is currently uncontrolled. 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. Any condition, including other inflammatory diseases or dermatologic conditions, which confounds the ability to interpret data from the study, including other types of psoriasis (ie, erythrodermic, guttate, inverse, or pustular psoriasis), other than plaque psoriasis. Prior history of suicide attempt at any time in the subject's life time prior to signing the informed consent and randomization, or major psychiatric illness requiring hospitalization within the last 3 years prior to signing the informed consent. Pregnant or breast feeding. Active substance abuse or a history of substance abuse within 6 months prior to signing the informed consent. Malignancy or history of malignancy, except for: treated (ie, cured) basal cell or squamous cell in situ skin carcinomas; treated (ie, cured) cervical intraepithelial neoplasia (CIN) or carcinoma in situ of the cervix with no evidence of recurrence within 5 years of signing the informed consent. Topical therapy within 2 weeks of randomization (including, but not limited to, topical corticosteroids, retinoids or vitamin D analog preparations, tacrolimus, pimecrolimus, or anthralin/dithranol). Use of phototherapy within 4 weeks prior to randomization. Use of any investigational drug within 4 weeks prior to randomization, or 5 pharmacokinetic/pharmacodynamic half-lives, if known (whichever is longer). Prolonged sun exposure or use of tanning booths, which may confound the ability to interpret data from the study. Prior treatment with apremilast.

Ages Eligible for Study
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Minimum Age: 18 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<br>Apremilast 30 mg tablets orally twice daily (BID) weeks 0 to 52. | Drug: Apremilast<br>* Apremilast 30 mg tablets orally twice daily (BID) weeks 0 to 52.<br>* Other names: CC-10004, Otzela;Drug: Placebo<br>* Participants randomized to the placebo treatment group received placebo tablets (identical in appearance to the apremilast 30 mg tablets) orally BID for from weeks 0-16.<br>Drug: Placebo-Apremilast<br>* At Week 16, those randomized to placebo were switched to apremilast 30mg BID for an additional 36 weeks (52 weeks total)<br>* Other names: CC-10004;|
| Placebo Comparator: Placebo<br>Placebo tablets BID during Weeks 0 to 16; at week 16, placebo participants were switched to apremilast 30 mg tablets BID for 36 weeks (from week 16 to week 52) | Drug: Placebo<br>* Participants randomized to the placebo treatment group received placebo tablets (identical in appearance to the apremilast 30 mg tablets) orally BID for from weeks 0-16.<br>Drug: Placebo-Apremilast<br>* At Week 16, those randomized to placebo were switched to apremilast 30mg BID for an additional 36 weeks (52 weeks total)<br>* Other names: CC-10004;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Percentage Change From Baseline in the Product of BSA (%) and the sPGA Which is Considered as the Total Psoriasis Severity Index 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 participant's hand (entire palmar surface or handprint including the fingers), which equates to approximately 1% of total body surface area. The sPGA is a 6-point scale ranging from 0 (clear), 1 (almost clear), 2 (mild), 3 (moderate), to 4 (severe), 5 (very severe) incorporating a separate assessment of the severity of the three primary signs of the plaques of all involved areas: erythema, scaling and plaque elevation with an overall sPGA calculated as (E + I + D)/3. Scores for each assessment are rounded to the nearest whole number to result in the final score. The range of BSA*sPGA mean percentage change from baseline to week 16 (end of phase) were -100 to 344.4 and -100 to 100 for the placebo and apremilast groups respectively. Higher scores represented worse outcomes. | Baseline to Week 16 (end of phase) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in the Dermatology Life Quality Index (DLQI) Total Score at 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. | Baseline to Week 16 (end of phase) | 
| Percentage of Participants Who Achieved a sPGA Score of Clear (0) or Almost Clear (1) at Week 16 From Baseline | The sPGA is an assessment by the investigator of the overall disease severity at the time of evaluation. Erythema (E), induration (I), and desquamation (D) are scored on a 6-point scale, ranging from 0 (clear) to 5 (very severe), with an overall sPGA calculated as (E + I + D)/3. Scores for each assessment are averaged and rounded to the nearest whole number to result in the final sPGA score. | Baseline to Week 16 (end of phase) | 
| Percentage of Participants Who Achieved a Clear (0) or Very Mild (1) on Patient Global Assessment (PtGA) Scale at Week 16 From Baseline | The PtGA response rate is defined as the percentage of participants achieving 0 (clear) or 1 (very mild) on the PtGA scale at Week 16. The PtGA is the assessment by the participant of the overall disease severity at the time of evaluation. The PtGA is a 5-point scale ranging from 0 (clear) to 4 (severe). | Baseline to Week 16 (end of phase) | 
| Mean Change From Baseline in Pruritus Visual Analog Scale (VAS) | The Pruritus VAS assessment was conducted at the baseline visit and each post-baseline visit. The participant was asked to place a vertical stroke on a 100 mm VAS on which the left-hand boundary (0) represents no itch, and the right-hand boundary (100) represents itch as severe as can be imagined. The distance from the mark to the left-hand boundary will be recorded. The Pruritus VAS score ranges from 0 to 100. Higher scores correspond to more severe symptom. | Baseline to Weeks 1 and 16 (end of phase) | 
| Percentage of Participants With Scalp Psoriasis Who Achieved a Clear (0) or Minimal (1) on Scalp Physician's Global Assessment (ScPGA) Scale at Week 16. | The ScPGA assessed scalp involvement, if present at baseline. The 6-point ScPGA scale includes three dimensions (Plaque Thickening, Scaling, and Erythema) and a global assessment. Scores range from 0 (clear), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe), to 5 (very severe). Analysis of ScPGA was restricted to the participants with scalp involvement at baseline. | Baseline to Week 16 (end of phase) | 
| Treatment Satisfaction Questionnaire for Medication (TSQM) Version II at Week 16 | The TSQM version II is an 11-question self-administered instrument to understand a participation's satisfaction with the current therapy. The TSQM scale comprises four domains, on which participants evaluate their medication (i.e., effectiveness, side effects, convenience and global satisfaction. TSQM scores range from 0 to 100 for each domain; a higher score mean indicates higher satisfaction with treatment. | Baseline to Week 16 (end of phase) | 
| Treatment Satisfaction Questionnaire for Medication (TSQM) Version II at Week 52 | The TSQM version II is an 11-question self-administered instrument to understand a participants satisfaction on the current therapy. The TSQM scale comprises four domains, on which participants evaluate their medication (i.e., effectiveness, side effects, convenience and global satisfaction. TSQM scores range from 0 to 100 for each domain; a higher score indicates higher satisfaction with treatment. | Baseline to week 52 | 
| Mean Percentage Change From Baseline in Psoriasis Area Severity Index Score (PASI) at Week 16 | The PASI score 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. 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). PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. | Baseline to Week 16 (end of phase) | 
| Percentage of Participants Who Achieved at Least a 50% Improvement (Response) in the Psoriasis Area and Severity Index (PASI)-50 From Baseline at Week 16. | The PASI score 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. 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). PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. | Baseline to Week 16 (end of phase) | 
| Percentage of Participants Who Achieved at Least a 75% Improvement (Response) in the Psoriasis Area and Severity Index (PASI)-75 From Baseline at Week 16 | The PASI score 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. 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). PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. | Baseline to Week 16 (end of phase) | 
| Mean Percentage Change From Baseline in the Product of BSA (%) x sPGA at Week 52 | BSA is a measurement of involved skin. The overall BSA affected by psoriasis is 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. The sPGA is a 6-point scale ranging from 0 (clear), 1 (almost clear), 2 (mild), 3 (moderate), to 4 (severe), 5 (very severe) incorporating a separate assessment of the severity of the three primary signs of the plaques of all involved areas: erythema, scaling and plaque elevation with an overall sPGA calculated as (E + I + D)/3. Scores for each assessment are rounded to the nearest whole number to result in the final score. | Baseline to Week 52 | 
| Percentage of Participants With Scalp Psoriasis Who Were Initially Randomized to Apremilast and Maintained the Scalp Physician's Global Assessment (ScPGA) Response From Week 16 to Week 52. | The ScPGA will assess scalp involvement, if present at baseline. The 6-point ScPGA scale includes three dimensions (Plaque Thickening, Scaling, and Erythema) and a global assessment with scores range from 0 (clear), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe), to 5 (very severe). Analysis of ScPGA is restricted to the participants with scalp involvement at baseline. | Week 16 to Week 52 | 
| Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs) During the Placebo Controlled Phase | Treatment-Emergent Adverse Events (TEAEs) are defined as any AEs that begin or worsen on or after the start of study drug through 28 days after the last dose of study drug or study treatment discontinuation date, whichever was later. 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/birth defect, or is a condition that may jeopardize the patient or may require intervention to prevent one of the outcomes listed above. | From first dose of study drug to Week 16; maximum duration of exposure was 20.1 weeks during placebo controlled phase | 
| Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) During the Apremilast-Exposure Phase | Treatment-Emergent Adverse Events (TEAEs) are defined as any AEs that begin or worsen on or after the start of study drug through 28 days after the last dose of study drug or study treatment discontinuation date, whichever was later. 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/birth defect, or is a condition that may jeopardize the patient or may require intervention to prevent one of the outcomes listed above. | Date of first dose of apremilast during the placebo controlled phase or date of first dose of apremilast after week 16; overall maximum duration of exposure was 61.5 weeks during apremilast-exposure phase | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Parapsoriasis, Plaque Psoriasis, CC-10004, Apremilast, Moderate Plaque Psoriasis, Safety