Study for Treatment With Calcipotriol/Betamethasone Dipropionate Gel in Korean Patients With Psoriasis Vulgaris

Study Overview
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Brief Summary
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The combination of calcipotriol and betamethasone dipropionate used in an ointment formulation (Daivobet® ointment) has shown to have an excellent efficacy and safety in the short-term and long-term management of psoriasis vulgaris. A newly developed gel formulation (Xamiol® gel) of calcipotriol and betamethasone dipropionate has recently been approved and marketed in Korea as a topical treatment of moderate to severe scalp psoriasis and non-scalp psoriasis vulgaris. Xamiol® gel, the investigational product (IP) used in this study, prevents keratinization by normalizing the reproduction cycle of skin cells. It also relieves itching associated with psoriasis. Xamiol® gel was initially approved for treatment of moderate to severe scalp psoriasis and its label was extended to non-scalp psoriasis vulgaris in October 2012. Since patient compliance is one of the important factors in achieving effective outcomes in the treatment of psoriasis, the once daily dosing of Xamiol® gel is expected to enhance compliance and treatment outcomes as well as to provide a safe and effective therapeutic option.

Detailed Description
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Psoriasis is a disease difficult to cure and is usually recurrent and therefore, a continued management is crucial. An evidence-based approach is important for appropriate treatments of patient with psoriasis. However, there is a lack of response data for the topical treatments in Asian patients with psoriasis, and no treatment guidelines available. Therefore, routine topical treatments, instead of patient-specific treatments, are usually applied, which may result in treatment failure. In this regard, it is imperative to conduct a study to assess topical treatments in Korean patients with psoriasis vulgaris in terms of efficacy and side effects. Furthermore, psoriasis patients in Korea, mostly small plaque types, may exhibit different disease activities and response outcomes and accordingly require different treatment options as compared to Western populations whose dominant psoriasis type is large plaque type. Thus, a study in Korean patients with psoriasis may reveal an interesting finding. In order to investigate optimal maintenance regimens for the topical treatment of Korean patients with psoriasis vulgaris, we are planning this study which evaluates the efficacy of three 8-week maintenance regimens containing Xamiol® gel (PRN treatment group, Continuous treatment group and Twice weekly treatment group) in patients who have become Responder after 8-week induction therapy with Xamiol® gel (Responder). The primary objective of this study is to evaluate the percentages of Responder* at week 16, as assessed by Investigator's Global Assessment of Disease Severity (IGA), in three different 8-week maintenance regimens of Xamiol® gel after 8-week induction treatment with Xamiol® gel in patients with psoriasis vulgaris. * Responder is defined as subjects with clear or almost clear according to IGA. Secondary study objectives is to evaluate efficacy, % of Relapse and time to Relapse, PGA, Patient Compliance, Safety and Quality of Life (DLQI and TSQM) in three arms with calcipotriol/betamethasone dipropionate combination gel treatment in Korean patients with chronic plaque psoriasis of the body.

Official Title
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Investigator Initiated Study for Optimal Maintenance Treatment With Calcipotriol /Betamethasone Dipropionate Gel in Korean Patients With Psoriasis Vulgaris

Conditions
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Psoriasis Vulgaris

Intervention / Treatment
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* Drug: Calcipotriol/betamethasone dipropionate gel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects aged 19 years and above Clinical diagnosis of stable psoriasis vulgaris of at least 4 weeks duration involving the non-scalp regions of the body (trunk and/or limbs) amenable to treatment with a maximum of 100 g of topical medication per week at screening An investigator's global assessment of disease severity(IGA) of at least mild on the body (trunk and/or limbs) at Day 0 (Baseline) Signed written informed consent prior to performance of any study-specific procedures or assessments, and must be willing to comply with treatment and follow up Able to communicate with the investigator and understand and comply with the requirements of the study Women of childbearing potential must have a negative pregnancy test and must use adequate contraception during the treatment phase of the study and for at least 1 week after the last application of study medication Exclusion Criteria: Body surface area (BSA) > 10 % or Psoriasis Area and Severity Index (PASI) > 10 at baseline * The palm of one hand is approximately 1 percent of the body surface area Subjects with unstable forms of psoriasis including guttate, erythrodermic, exfoliative and pustular psoriasis, or psoriatic arthritis Subjects with known disorders of calcium metabolism/hypercalcemia Subjects with hypersensitivity to the active substances or to any of the excipients of the investigational products Systemic treatment with biological therapies with a possible effect on psoriasis vulgaris within the following time periods prior to baseline visit etanercept - within 4 weeks prior to baseline adalimumab, alefacept, infliximab - within 2 months prior to baseline ustekinumab - within 4 months prior to baseline investigational product - within 4 weeks/5 half-lives (whichever is longer) prior to baseline Systemic treatment with all other therapies with a possible effect on psoriasis vulgaris (e.g., corticosteroids, retinoids, methotrexate, cyclosporine and other immunosuppressants) within 4 weeks prior to baseline visit Phototherapy within the following time periods prior to baseline visit PUVA or Grenz ray - within 4 weeks UV-B - within 2 weeks Any topical treatment of the trunk and/or limbs (except for emollients) within 2 weeks prior to baseline visit Topical treatment for other relevant skin disorders on the face and flexures (e.g., facial and flexural psoriasis, eczema) with class 1- 5 corticosteroids or vitamin D analogues within 2 weeks prior to baseline visit Topical treatment for other relevant skin disorders on the scalp (e.g. scalp psoriasis) with class 1-5 corticosteroids, vitamin D analogues within 2 weeks prior to baseline visit Subjects with severe renal insufficiency Subjects with severe hepatic disorders Subjects with a confounding skin condition or disorders against psoriasis evaluation Subjects with viral (e.g. herpes or varicella) lesions of the skin, fungal or bacterial skin infections, parasitic infections on the treatment area Subjects with skin manifestations in relation to tuberculosis or syphilis on the treatment area Subjects with perioral dermatitis, atrophic skin, striae atrophicae on the treatment area Subjects with fragility of skin veins, ichthyosis on the treatment area Subjects with acne vulgaris, rosacea, wounds, ulcers, perianal and genital pruritus on the treatment area Planned initiation of, or changes to, concomitant medication that could affect psoriasis vulgaris (e.g. beta blockers, anti-malarials, lithium, ACE inhibitors) during the study Pregnant or lactating female subjects Subjects who are planning a pregnancy during the entire study period

Ages Eligible for Study
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Minimum Age: 19 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PRN treatment<br>Group 1: PRN treatment Apply Xamiol® gel (Calcipotriol/betamethasone dipropionate gel) once daily as needed (PRN) | Drug: Calcipotriol/betamethasone dipropionate gel<br>* All enrolled subjects will receive Xamiol® gel once daily for 8 weeks during the induction period and then will be assessed according to IGA at the end of 8-week induction period. Those subjects determined to be Responder by IGA will be randomized to one of the following three treatment groups and they will continue their therapy with randomized maintenance regimens for the duration of additional 8 weeks.<br>* Other names: Xamiol gel;|
| Experimental: Continuous treatment<br>Group 2: Continuous treatment Apply Xamiol® gel (Calcipotriol/betamethasone dipropionate gel)once daily | Drug: Calcipotriol/betamethasone dipropionate gel<br>* All enrolled subjects will receive Xamiol® gel once daily for 8 weeks during the induction period and then will be assessed according to IGA at the end of 8-week induction period. Those subjects determined to be Responder by IGA will be randomized to one of the following three treatment groups and they will continue their therapy with randomized maintenance regimens for the duration of additional 8 weeks.<br>* Other names: Xamiol gel;|
| Experimental: Weekends treatment<br>Group 3: Weekends treatment (twice weekly) Apply Xamiol® gel (Calcipotriol/betamethasone dipropionate gel) once daily at weekends (on Saturdays and Sundays) | Drug: Calcipotriol/betamethasone dipropionate gel<br>* All enrolled subjects will receive Xamiol® gel once daily for 8 weeks during the induction period and then will be assessed according to IGA at the end of 8-week induction period. Those subjects determined to be Responder by IGA will be randomized to one of the following three treatment groups and they will continue their therapy with randomized maintenance regimens for the duration of additional 8 weeks.<br>* Other names: Xamiol gel;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Responder (subjects with a grade of clear or almost clear) according to IGA at Week 16 | The primary objective of this study is to evaluate the percentages of Responder* at week 16, as assessed by Investigator's Global Assessment of Disease Severity (IGA), in three different 8-week maintenance regimens of Xamiol® gel after 8-week induction treatment with Xamiol® gel in patients with psoriasis vulgaris. | Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Investigator's global assessment of disease severity | To evaluate the change of disease severity assessed by IGA in induction treatment phase and compare the IGA disease severity of three different maintenance regimens in the maintenance treatment phase. | Week 0, 4, 8, 12 and 16 | 
| Percentage of disease relapse | To evaluate descriptive statistics of three different regimens in the maintenance treatment phase and compare percentage of relapse in threee different regimens. | Week 0, 4, 8, 12 and 16 | 
| Patient's global assessment of disease severity | To evaluate the change of disease severity assessed by PGA in induction treatment phase and compare the PGA disease severity of three different maintenance regimens in the maintenance treatment phase. | Week 0, 4, 8, 12 and 16 | 
| Change in Psoriasis Area and Severity Index (PASI) score from Baseline to Week | To evaluate the change of PASI in induction treatment phase and compare the PASI of three different maintenance regimens in the maintenance treatment phase. | Week 0, 4, 8, 12 and 16 | 
| Percent of subjects achieving a 75% improvement in the Psoriasis Area and Severity Index (PASI) score | To evaluate the change of PASI75 from week 4 to week 8 in induction treatment phase and compare PASI75 in three different regimens in the maintenance treatment phase. | Week 0, 4, 8, 12 and 16 | 
| Time to relapse | To evaluate descriptive statistics of three different regimens in the maintenance treatment phase and compare the time to relapse in threee different regimens. | Week 0, 4, 8, 12 and 16 |