A Phase III Study in Subjects With Mild to Moderate Psoriasis.

Study Overview
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Brief Summary
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A randomized, assessor blind, parallel group, three arms, active and placebo controlled study with objective to demonstrate therapeutic non-inferiority of AKP02 cutaneous spray (calcipotriol 50 μg/g + betamethasone 0.5 mg/g/ AKVANO) versus Enstilar cutaneous foam (calcipotriol 50 μg/g + betamethasone 0.5 mg/g) in subjects with mild to moderate plaque psoriasis.

Detailed Description
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Eligible subjects (in total 294) will be randomized in a 3:3:1 fashion to receive AKP02 cutaneous spray, Enstilar cutaneous foam or the AKVANO vehicle spray, respectively. The randomization will be stratified by skin type (Fitzpatrick skin type I-III and Fitzpatrick skin type IV-VI). At least 25 % of the subjects randomized in the study should belong to Fitzpatrick skin type I-III and at least 25 % to Fitzpatrick skin type IV-VI.

Official Title
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A Randomized Phase III, Three-parallel Arm, Assessor Blind, Multi-centre Study to Evaluate the Efficacy, Safety and Tolerability of AKP02 Cutaneous Spray Versus Enstilar Cutaneous Foam in Subjects With Mild to Moderate Psoriasis.

Conditions
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Mild to Moderate Psoriasis

Intervention / Treatment
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* Drug: AKP02/AKVANO cutaneous spray (calcipotriol 50 μg/g + betamethasone 0.5 mg/g/ AKVANO)
* Drug: Enstilar Topical Product (calcipotriol 50 μg/g + betamethasone 0.5 mg/g)
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or non-pregnant female subjects aged >18 years having either Fitzpatrick skin type I-III or IV-VI at the time of screening. A clinical diagnosis of stable (at least 6 months) psoriasis vulgaris on body, or body and scalp, involving 5 to 10% of body surface area (BSA) and PASI ≤10., that does not include the face, axilla and groin areas. Mild or moderate Psoriasis on Physician Global Assessment (PGA) score (grade 2 - 3). A plaque elevation of at least moderate severity (grade ≥ 3) at the target lesion site. The most severe lesion at Baseline should be identified as the target lesion. Subjects must be willing to provide written informed consent. Subjects must be willing and able to understand and can comply with study requirements, apply the medication as instructed and be able to complete the study. Subject must be in general good health as judged by the Investigator, based on medical history and physical examination. Exclusion Criteria: Subject with history of hypersensitivity to betamethasone or calcipotriol or any component of the test or reference product or placebo. Current diagnosis of unstable forms of psoriasis in the treatment area including guttate, erythrodermic, exfoliative, or pustular psoriasis. Subjects with diagnosis of mild to moderate psoriasis only in the scalp area. Other inflammatory skin disease in the treatment area that may confound the evaluation of the psoriasis vulgaris (e.g., atopic dermatitis, contact dermatitis, tinea corporis and seborrheic dermatitis). Presence of pigmentation, extensive scarring, pigmented lesions, or sunburn in the treatment areas, which could interfere with the rating of efficacy parameters. Subject with history of psoriasis unresponsive to topical treatments. Subject with psoriasis lesions predominantly on palms and soles or palmo-plantar area. Subjects with the diagnosis pustulosis palmo-plantaris Subject in need of systemic treatment Ongoing use of other psoriasis treatment including but not limited to topical or systemic corticosteroids, other topical medications (i.e. coal tar), oral or biologic medications for the treatment of psoriasis, and UV therapy. Use of oral estrogen therapy, excluding oral contraceptive pills Females who are pregnant, nursing, or planning a pregnancy Females of childbearing potential who do not agree to utilize an adequate form of contraception. Current significant medical problems that, in the discretion of the investigator, would put the subject at significant risk Use of any investigational drug within 4 weeks prior to randomization, or 5 pharmacokinetic/pharmacodynamics half-lives, if known (whichever is longer) Current or past history of hypercalcemia, calcium metabolism disorder, vitamin D toxicity, severe renal insufficiency, or severe hepatic disorders. Current immunosuppression Use of biologic treatment for psoriasis (e.g., infliximab, adalimumab, alefacept) within six months prior to Baseline. Use of: 1) chemotherapy, or 2) radiation therapy, within three months prior to Baseline. Use of: 1) immunosuppressive drugs (e.g., tacrolimus, pimecrolimus), or 2) oral retinoids, within two months prior to Baseline. Use of: 1) systemic steroids, 2) systemic antibiotics, 3) other systemic antipsoriatic treatment, 4) PUVA therapy, 5) UVB therapy, or 6) systemic anti-inflammatory agents, within one month prior to Baseline. Use of: 1) topical anti-psoriatic drugs (e.g., salicylic acid, anthralin, coal tar, calcipotriol, tazarotene), 2) topical corticosteroids, or 3) topical retinoids, within 2 weeks prior to Baseline. Use of medicated shampoos with possible effect on psoriasis Subject with positive serology tests like HIV, HCV & HBsAg.

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
Interventional Model Description: A randomized, assessor blind, parallel group, three arms, active and placebo controlled study
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AKP02<br>cutaneous spray (calcipotriol 50 μg/g + betamethasone 0.5 mg/g/ AKVANO) | Drug: AKP02/AKVANO cutaneous spray (calcipotriol 50 μg/g + betamethasone 0.5 mg/g/ AKVANO)<br>* Topical cutaneous spray<br>Drug: Enstilar Topical Product (calcipotriol 50 μg/g + betamethasone 0.5 mg/g)<br>* Topical foam<br>Other: Placebo<br>* Placebo cutaneous spray<br>|
| Active Comparator: Enstilar<br>cutaneous foam (calcipotriol 50 μg/g + betamethasone 0.5 mg/g) | Drug: AKP02/AKVANO cutaneous spray (calcipotriol 50 μg/g + betamethasone 0.5 mg/g/ AKVANO)<br>* Topical cutaneous spray<br>Drug: Enstilar Topical Product (calcipotriol 50 μg/g + betamethasone 0.5 mg/g)<br>* Topical foam<br>Other: Placebo<br>* Placebo cutaneous spray<br>|
| Placebo Comparator: Placebo<br>cutaneous spray | Drug: AKP02/AKVANO cutaneous spray (calcipotriol 50 μg/g + betamethasone 0.5 mg/g/ AKVANO)<br>* Topical cutaneous spray<br>Drug: Enstilar Topical Product (calcipotriol 50 μg/g + betamethasone 0.5 mg/g)<br>* Topical foam<br>Other: Placebo<br>* Placebo cutaneous spray<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage change in Psoriasis Area and Severity Index (PASI) score | Percentage change in Psoriasis Area and Severity Index (PASI) score from baseline/randomization to the end of treatment between test product (AKP02 cutaneous spray) and comparator product (Enstilar cutaneous foam). High score is worse | From baseline/randomization to Week 4 (Day 29±4) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage change in Psoriasis Scalp Severity Index (PSSI) scores | Percentage change in Psoriasis Scalp Severity Index (PSSI) scores from baseline to end of treatment. High score is worse | From date of randomization until Week 4 (Day 29±4) post-randomization | 
| Change in Physician's global assessment (PGA) | Change in Physician's global assessment (PGA) at end of treatment compared to baseline High score is worse | From date of randomization until Week 4 (Day 29±4) post-randomization | 
| Change in Scalp Physician's global assessment (ScPGA) | Change in Scalp Physician's global assessment (ScPGA) at end of treatment compared to baseline High score is worse | From date of randomization until Week 4 (Day 29±4) post-randomization | 
| Frequency of adverse events and serious adverse events | Frequency of adverse events and serious adverse events or any event of clinical significance | From date of randomization until end of study |