A Study of the Efficacy and Safety of Apremilast (CC-10004) in Subjects With Moderate to Severe Plaque Psoriasis of the Scalp

Study Overview
=================
Brief Summary
-----------------
This is a Phase 3, multicenter, randomized, placebo-controlled, double-blind study of the efficacy and safety of apremilast (CC-10004) in subjects with moderate to severe plaque psoriasis of the scalp. Approximately 300 subjects with moderate to severe plaque psoriasis of the scalp will be randomized 2:1 to receive either apremilast 30 mg twice daily (BID) or placebo for the first 16 weeks.

Detailed Description
-----------------
The study will consist of four phases: Screening Phase - up to 35 days Double-blind Placebo-controlled Phase- Weeks 0 to 16 Subjects will receive treatment with one of the following: apremilast 30 mg tablets orally BID or placebo tablets (identical in appearance to apremilast 30 mg tablets) orally BID Apremilast Extension Phase - Weeks 16 to 32 All subjects who had received placebo during the placebo-controlled phase will be switched to apremilast 30 mg BID (or continue with) apremilast. At Week 16, all subjects will maintain this dosing through Week 32. Observational Follow-up Phase Four-week Post-Treatment Observational Follow-up Phase for all subjects who complete the study or discontinue from the study early.

Official Title
-----------------
A Phase 3, Multi-Center, Randomized, Placebo-Controlled, Double-Blind, Study of the Efficacy and Safety of Apremilast (CC-10004) in Subjects With Moderate to Severe Plaque Psoriasis of the Scalp

Conditions
-----------------
Psoriasis

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects must satisfy the following criteria to be enrolled in the study: Males or females, ≥ 18 years of age at the time of signing the informed consent document Be willing and able to adhere to the study visit schedule and other protocol requirements. Have a diagnosis of moderate to severe plaque psoriasis of the scalp at screening and baseline Must be a candidate for phototherapy and/or systemic therapy for either body or scalp psoriasis lesions. Have moderate to severe plaque psoriasis at screening and baseline Must be in good health (except for psoriasis) as judged by the Investigator, based on medical history, physical examination, 12-lead electrocardiogram (ECG), clinical laboratories, and urinalysis Must meet laboratory criteria Females of childbearing potential (FCBP)* must have a negative pregnancy test at screening and baseline. While on investigational product (IP) 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. *A female of childbearing potential is a sexually mature female who 1) has not undergone a hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy (the surgical removal of both ovaries) or 2) has not been postmenopausal for at least 24 consecutive months (that is, has had menses at any time during the preceding 24 consecutive months). ** The female subject's chosen form of contraception must be effective by the time the female subject is randomized into the study (for example, hormonal contraception should be initiated at least 28 days before randomization). Exclusion Criteria: The presence of any of the following will exclude a subject from enrollment: Other than psoriasis, history of any clinically significant uncontrolled disease. 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 Hepatitis B surface antigen positive at screening Anti-hepatitis C antibody positive at screening Active tuberculosis (TB) or a history of incompletely treated TB Clinically significant abnormality on 12-lead electrocardiogram (ECG) at 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 signing the informed consent form. Bacterial infections requiring treatment with oral or injectable antibiotics, or significant viral or fungal infections, within 4 weeks of signing the informed consent form. Malignancy or history of malignancy, except for treated (i.e., cured) basal cell or squamous cell in situ skin carcinomas or treated (i.e., 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. 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. Psoriasis flare/rebound within 4 weeks of signing the informed consent form or between the screening and baseline visits. Topical therapy within 2 weeks prior to randomization; Conventional systemic therapy for psoriasis within 4 weeks prior to randomization; Intralesional corticosteroids on the scalp within 2 weeks prior to randomization; Phototherapy treatment of body or scalp psoriasi lesions within 4 weeks prior to randomization; Biologic therapy between 12 weeks to 24 weeks prior to randomization Use of any investigational drug beginning 4 weeks prior to randomization, or 5 pharmacokinetic/pharmacodynamic half-lives, if known (whichever is longer) Prolonged sun exposure or use of tanning booths or other ultraviolet (UV) light sources Prior treatment with apremilast History of allergy or hypersensitivity to any components of the Investigational product.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Apremilast 30 mg BID<br>Apremilast 30 mg tablets orally twice daily (BID) during Weeks 0 to 32 | Drug: Apremilast<br>* Apremilast 30 mg tablets BID from weeks 0 to 32.<br>* Other names: CC-10004;Other: Placebo<br>* Placebo tablets twice daily (BID) for 16 weeks; placebo participants were switched to apremilast 30 mg at week 16.<br>|
| 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 16 weeks (from Week 16 to Week 32) | Other: Placebo<br>* Placebo tablets twice daily (BID) for 16 weeks; placebo participants were switched to apremilast 30 mg at week 16.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Scalp Physician Global Assessment (ScPGA) Score of Clear (0) or Almost Clear (1) With at Least a 2-Point Reduction From Baseline | The ScPGA is a measurement of overall scalp involvement by the investigator at the time of evaluation. The ScPGA is a 5-point scale ranging from 0 (clear) to 4 (severe), incorporating an assessment of the severity of the 3 primary signs of the disease: erythema, scaling, and plaque elevation. When making the assessment of overall scalp severity, the investigator factored in areas that had already been cleared (ie, had scores of 0), not limited to the evaluation of remaining lesions for severity; consequently, the severity of each sign was averaged across all areas of involvement, including cleared lesions. | Baseline to Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With ≥ 4-Point Reduction (Improvement) From Baseline in the Whole Body Itch Numeric Rating Score at Week 16 | The Whole Body Itch NRS scale is an 11-point scale to assess whole body itch. The scale ranges from 0-10, where 0 represents no itch, and 10 represents the worst imaginable itch, and a 4-point change from baseline was shown to be optimal for demonstrating a level of clinically meaningful improvement in itch severity. NRS response was defined as a ≥ 4-point reduction (improvement) from baseline. | Baseline to Week 16 | 
| Percentage of Participants With ≥ 4-Point Reduction (Improvement) From Baseline in the Scalp Itch Numeric Rating Score (NRS) at Week 16 | The scalp itch NRS is a 11-point scale to assess scalp itch. The scale ranges from 0-10, where 0 represents no itch, and 10 represents the worst imaginable itch. | Baseline to Week 16 | 
| Percentage of Participants With ≥ 4-Point Reduction (Improvement) From Baseline in the Whole Body Itch NRS Score by Visit in the Placebo-Controlled Phase | The Whole Body Itch NRS scale is a 11-point scale to assess whole body itch. The scale ranges from 0-10, where 0 represents no itch, and 10 represents the worst imaginable itch, and a 4-point change from baseline was shown to be optimal for demonstrating a level of clinically meaningful improvement in itch severity. | Baseline to Weeks 2, 4, 6, 8 and 12 | 
| Percentage of Participants With ≥ 4-Point Reduction (Improvement) From Baseline in the Scalp Itch NRS Score by Visit in the Placebo-Controlled Phase | The scalp itch NRS is a 11-point scale to assess scalp itch. The scale ranges from 0-10, where 0 represents no itch, and 10 represents the worst imaginable itch. | Baseline to Weeks 2, 4, 8 and 12 | 
| Change From Baseline in Dermatological Life Quality Index (DLQI) Total Score at Week 16 | DLQI is 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 subject 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 was derived by summing all item scores, and 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 | 
| Number of Participants With Treatment Emergent Adverse Events (TEAE) During the Placebo-Controlled Phase | 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. 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. The severity of AEs was assessed based on the following scale: Mild = asymptomatic or mild symptoms, clinical or diagnostic observations only; Moderate = symptoms cause moderate discomfort; Severe = could be non-serious or serious) = symptoms causing severe pain discomfort. | Week 0 to Week 16; mean duration of exposure was 14.5 weeks and 14.6 weeks for participants randomized to placebo and apremilast respectively. | 
| Number of Participants With Treatment Emergent Adverse Events During the Apremilast-Extension Phase | 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. 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. The severity of AEs was assessed based on the following scale: Mild = asymptomatic or mild symptoms, clinical or diagnostic observations only; Moderate = symptoms cause moderate discomfort; Severe = could be non-serious or serious) = symptoms causing severe pain discomfort. | Weeks 16 to Week 32; the mean treatment duration was 14.6 weeks and 15.3 weeks in the APR 30/APR 30 BID and placebo/APR 30 BID arms, respectively | 
| Number of Participants With Treatment Emergent Adverse Events During the Apremilast-Exposure Period | The apremilast-exposure period started on the date of the first dose of apremilast (Week 0 for participants originally randomized to apremilast or Week 16 for participants originally randomized to placebo) to the last dose of apremilast. 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. 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. The severity of AEs was assessed based on the following scale: Mild = asymptomatic or mild symptoms, clinical or diagnostic observations only; Moderate = symptoms cause moderate discomfort; Severe = could be non-serious or serious) = symptoms causing severe pain discomfort. | Week 0 to 32; | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Plaque Psoriasis, Scalp, Double-Blind, Efficacy, Safety, CC-10004, Apremilast, Otezla, Itch, Head