CLINICAL STUDY REPORT Efficacy of Psorioderm cream in treatment of mild to moderate plaque psoriasis which does not require biological therapy

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1 DEBRECENI EGYETEM ORVOS- ÉS EGÉSZSÉGTUDOMÁNYI CENTRUM Bőrgyógyászati Klinika Igazgató: Dr. Remenyik Éva egyetemi tanár UNIVERSITY OF DEBRECEN MEDICAL AND HEALTH SCIENCE CENTRE Department of Dermatology Head of Department: Eva Remenyik M.D., DSci. H-032 Debrecen, Nagyerdei krt. 9. tel.: igazgató: (3-52) , porta: (3-52) , fax: (3-52) CLINICAL STUDY REPORT Efficacy of Psorioderm cream in treatment of mild to moderate plaque psoriasis which does not require biological therapy Period I Objective: To assess the efficacy and safety of Psorioderm cream partly by placebo-controlled, double-blind, parallel-group, comparative study and by continuous routine application of Psorioderm cream in subjects with mild to moderate plaque psoriasis in a single-centre study. Principal investigator: Eva Remenyik, M. D., D.Sci., Head of the Department of Dermatology, University of Debrecen Medical and Health Science Centre Ethical considerations: The investigational product is cosmetics, therefore it is not obligatory to apply GCP (Good Clinical Practice) guidelines pertaining to the trial of pharmaceutical preparations. Despite, this study was conducted in accordance with GCP guidelines. Number of Ethics Committe approval: TUKEB /20-1EKU(15/PI/0/ Applied treatments: Period I placebo-controlled: All subjects apply both investigational products. The active ingredient is Psorioderm cream and placebo is the vehicle of Psorioderm cream. Period II: All subjects apply investigational products with active ingredient (Psorioderm shower gel, Psorioderm lotion, Psorioderm cream) to treat their psoriatic plaques every day. Period I: Method: Placebo-controlled, double-blind, parallel-group, comparative study Duration of study: March June 2011 Number of analyzed subjects: 29 subjects Diagnosis: mild to moderate plaque psoriasis which does not require biological therapy Duration of treatment: weeks Summary - conclusion: Based on these results, Psoriasis Severity Index (PSI) of analysed psoriatic plaques significantly improved compared to the base-line scores after a six-week application of the investigational products (Figure 1, Figure 2). PSI Psoriasis Severity Index *PGA Physician s Global Assessment (a six-point scale: 0 asymptomatic, 1-5 increasing severity ** VAS Visual Analog Scale assessment of subjects

2 Figure 1 Figure 2 1 A PSI értékek alakulása a kezelés során A 2.vizit után kezdődött meg a kezelési periódus és héten át (a.vizitig) tartott A vertikális oszlop a 95%-os konfidencia intervallumot jelöli Hatóanyagos kezelés 1 A PSI értékek alakulása a kezelés során A 2.vizit után kezdődött meg a kezelési periódus és héten át (a.vizitig) tartott A vertikális oszlop a 95%-os konfidencia intervallumot jelöli Placebo kezelés PSI pontértékek PSI pontértékek PSI_1 PSI_2 PSI_3 PSI_ PSI_5 PSI_ PSI_7 PSI_ VIZITEK [hetente] Figure 1 PSI scores at different stages of treatment Treatment period started after Visit 2 and lasted for six weeks (the end of the study Visit ) Vertical columns show 95 % confidence interval Treatment with Psorioderm cream PSI_1 PSI_2 PSI_3 PSI_ PSI_5 PSI_ PSI_7 PSI_ VIZITEK [hetente] Figure 2 PSI scores at different stages of treatment Treatment period started after Visit 2 and lasted for six weeks (the end of the study Visit ) Vertical columns show 95 % confidence interval Treatment with placebo The other two analyzed parameters (PGA* and VAS**) also decreased significantly by the end of the study (Figure, Figure 5). Figure Figure 5 9 VAS értékek alakulása a kezelés során Box-Whisker ábra medián kvartilisek PGA értékek alakulása a tanulmány során Box-Whisker ábra.5 medián kvartilisek VAS 5 PGA VAS_1 VAS_2 VAS_ 0.5 PGA_1 PGA_2 PGA_ Figure VAS scores at different stages of treatment Box-and-Whisker Plot Figure 5 PGA scores at different stages of treatment Box-and-Whisker Plot Consequently, Psorioderm cream significantly improved PSI of analysed psoriatic plaques (Figure 1). According to the investigators assessment, the subjects symptoms tend to decrease on PGA scores (Figure 5) and they experienced significant improvement as well (VAS) (Figure ). Treatment with Psorioderm cream caused more significant changes compared with placebo, however, considerable placebo effect was also revealed. Overall, Psorioderm cream containing vitamins, trace elements, salicylic acid and urea (Dead Sea salt) using twice daily, can alleviate the psoriatic symptoms. Furthermore, Psorioderm cream may reduce the requirements (application frequency) therefore the side effects of topical steroids, which are the most commonly used agents in psoriasis. 2

3 Discussion - Background Psoriasis, also known as psoriasis vulgaris, is a non-contagious, immune-mediated, inflammatory skin disease which affects 1-2% of the population in Hungary. Mild, moderate and severe clinical forms can be grouped. In the case of mild forms topical treatment, in moderate forms phototherapy and in severe cases systemic medications or parenteral biological therapy are recommended. Approximately three-quarters of patients have mild to moderate forms of psoriasis. In these cases, topical treatment is generally used. Symptoms limited to less than percent of the patients body surface area usually do not require systemic treatment. In Hungary, besides the conventional therapy of psoriasis containing sulphur, salicylic acid and tar, dithranol has a limited usage for outpatients. Except for topical emollients and topical steroids, ointment containing topical steroid and vitamin D derivative can also be prescribed. However, the disease is frequent, the number of active substances which can be used regularly rather few. Objective The aim of this study was to assess the efficacy and safety of Psorioderm cream by placebocontrolled, double-blind, parallel-group, comparative study (Period I) and by continuous routine application of the cream in subjects with mild to moderate plaque psoriasis in a single-centre study. The current report summarizes the data of Period I. Psorioderm cream and placebo were provided to subjects in identical, double-blinded packages. Two contralateral areas with symmetrical symptoms (Area 1, Area 2) were treated with both creams twice daily. Weekly follow-up visits were performed. At the first visit, physicians determined the severity of psoriasis and described demographic information. Subsequently, there was a washout phase without treatment for two weeks. The treatment started after the second visit and lasted for six weeks. Method To assess the efficacy, PSI was determined every week. PSI, influenced by the extent of exfoliation, skin inflammation and thickness, indicates objectively the severity of the disease (maximum: 2 points) on the analysed psoriatic area. At Visit 1, Visit 2 and Visit Visual Assessment Scale (VAS) and Physician Global Assessment (PGA) were determined. These parameters indicate the subjects and the physicians subjective opinion on the course of the disease. To assess safety, subjects reported any suspected side-effects and to assess compliance, physicians measured the weight loss of the creams at every visit. Study design Male and female subjects 1-5 years of age with mild to moderate plaque psoriasis who does not require biological therapy are enrolled in the study. The planned number of subjects who complete the study is 25. This study is a placebo-controlled, double-blind, self-controlled, single-centre study to assess the efficacy and safety of Psorioderm cream in 1 to 5 year-old male and female subjects with mild to moderate plaque psoriasis. The analysed areas and plaques should be easily accessible for the subjects (on chest, abdomen, extremities, etc.) and well demarcated from each other. Duration of the study was weeks divided to a two-week enrolment period and a -week treatment period. Total of eight visits were performed. Treatment - Results In the study, 29 subjects were enrolled of which 27 subjects completed Period I. One subject was excluded because of side-effects and another one dropped out due to inadequate compliance. The mean age of subjects (11 male and 1 female) completed the study was 7.7 years. All of them were Caucasians. The mean duration of psoriasis was 22.9 years. 3

4 On the affected skin of subjects, two symmetric areas (approximately x15 cm) were analysed. There had to be a large or several smaller psoriatic plaques on the observed area. Each of their size had to be at least cm 2 and they also had to be localized far from each other. On the enrolment, there was no significant difference between PSI scores of Area 1 (treated with Psorioderm cream, mean PSI: 15.2, median: 1) and Area 2 (treated with placebo, mean PSI: 15.2, median: ) (Figure 3). At the baseline the mean and the median of VAS scores were 5.52 and 5, the mean and the median of PGA scores were 3. and, respectively. Compliance was evaluated by a scale range from 1 to 5 at the end of the study. 2 subjects of 29 had adequate compliance (1 = "The preparation always was used as prescribed"). In one case, investigators reported the compliance not to be adequate (3 = "The preparation was occasionally used as prescribed"). The subjects agreed to neither sunbathe, nor use tanning devices, nor apply other topical creams with active ingredient during the study. There was significant reduction in PSI scores after the baseline treatment (at Visit 2) and it decreased steadily by Visit in both forms of treatment (Figure 1, Figure 2). Application of Psorioderm cream (Cream 1) leaded to greater change in PSI compare to placebo (Cream 2) (Figure 3). 1 A PSI értékek alakulása tanulmány során a két kezelési területen A hetente történtek A 2.vizit után kezdődött meg a kezelési periódus és hétig (.vizitig) tartott Vertikális oszlop a 95%-os konfidencia intervallumokat jelöli p=0. - NS 1 PSI pontérték 1 1.kezelés 2.kezelés PSI_1 PSI_2 PSI_3 PSI_ PSI_5 PSI_ PSI_7 PSI_ Figure 3 PSI scores at different stages of treatment on both treated areas Visits were performed weekly Treatment period started after Visit 2 and lasted for six weeks (the end of the study Visit ) Vertical columns show 95 % confidence interval

5 Assessment of VAS decreased significantly (p = 0.001) (Figure ). Regarding to the assessment of PGA, there was no detectable difference between the results of Visit 1 and Visit 2, however, it decreased significantly (p = ) at Visit (Figure 5). Consequently, Psorioderm cream significantly improved the PSI of analysed psoriatic plaques. According to the investigators assessment, the subjects symptoms tend to decrease on PGA scores and they experienced significant improvement as well. There was no serious adverse event. In one case, skin dryness occurred after four weeks leading to discontinuation of study treatment. Another subject had to be excluded because of bad compliance. The other 27 subjects had no complications and their compliance was adequate to the regulations. Subjects applied the test and reference creams on the analysed area twice daily for six weeks. They received new tubes at visits if they needed. Weighing the tubes on arrival, the amount of the applied creams was measured every week. On both treated areas, the amount of the creams used was steadily decreased from week to week. This reduction compared to baseline became significant (p = and p = 0.00) by Visit 7 and Visit. Overall, Psorioderm cream containing vitamins, trace elements, salicylic acid and urea (Dead Sea salt) using twice daily, can alleviate the psoriatic symptoms. Furthermore, Psorioderm cream may reduce the requirements (application frequency) therefore the side effects of topical steroids, which are the most commonly used agents in psoriasis. Attachments: 3 pages Debrecen, 5 July 2011 Eva Remenyik M.D., DSci. Head of Department of Dermatology University of Debrecen Medical and Health Science Centre 5