Clinical Trial to Assess Safety, Tolerability and the Pharmacodynamics Effect of Calcipotriol/Betamethasone Dipropionate in a New Administration Form in Subjects With Chronic Plaque Psoriasis.

Study Overview
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Brief Summary
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To assess safety, tolerability and pharmacodynamics effect of treatment with microarray patches containing calcipotriol and betamethasone dipropionate.

Official Title
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A Phase 1b, Randomised, Controlled, Assessor-blinded Proof of Principle Trial to Assess Safety, Tolerability and Pharmacodynamics Effects of Microarray Patches Containing Calcipotriol/Betamethasone Dipropionate in Descaled Skin of Adults With Chronic Plaque Psoriasis Over a 21-day Treatment Period

Conditions
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Psoriasis Vulgaris

Intervention / Treatment
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* Drug: Microarray patch A
* Drug: Microarray patch B
* Drug: Placebo
* Drug: Daivobet


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Subjects with psoriasis vulgaris in a chronic stable phase and mild to moderate plaque(s) covering a sufficient area to allocate 4 test fields on up to 3 comparable plaques. Men and women aged 18-70 years (inclusive). Sufficient target lesion(s) must be present on the trunk or extremities (excluding palms/soles); psoriatic lesions on the knees or elbows are not to be used as target lesions. Plaques to be treated should have a comparable thickness of the EPB of the inflammatory infiltrate of at least 200 μm. Plaques to be treated should have no more than a 2-fold difference in infiltrate thickness between the test fields. Physical examination of skin must be without abnormal, clinical significant findings other than psoriasis vulgaris unless the investigator considers an abnormality to be irrelevant to the trial outcome. Key Exclusion Criteria: Other skin disease noted on physical examination that is considered by the investigator to be relevant to the outcome of the trial. Subjects with acute psoriasis guttata, psoriasis punctata, psoriasis erythrodermatica, pustular, exfoliative or inverse psoriasis. History of psoriasis that was unresponsive or poorly responsive to topical treatments. Topical antipsoriatics are not permitted on the same body area as plaques to be treated during the 4 weeks before first treatment and during the trial. Systemic treatment with antipsoriatics e.g. corticosteroids, cytostatics, retinoids, dimethylfumarate, apremilast in the 3 months before first treatment and during the trial. Systemic treatment with biological treatments: rituximab within 12 months, ustekinumab or secukinumab within 6 months before first treatment and during the trial. Systemic treatment with biological treatments within 3 months before first treatment and during the trial. Systemic treatment with any other biological treatments within the period of 5 half-lives of the biological before first treatment and during the trial. UV-therapy or extensive exposure to UV radiation or sunlight within 4 weeks before first treatment and during the trial. Treatment with concomitant medication that may affect and provoke or aggravate psoriasis, unless on a stable dose for 3 months before trial medication initiation. Any other topical medication on the plaques to be treated during the trial. Clinically significant abnormal vital signs (blood pressure, and pulse) at screening (V1). History/symptoms of a clinically significant illness before first treatment (past 5 years) and during the trial that in the investigator's opinion may place the subject at risk. History/symptoms of a clinically significant illness before first treatment (past 5 years) and during the trial that in the investigator's opinion may influence the trial outcome. Other clinically significant abnormal laboratory results.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Crossover Assignment
Interventional Model Description: Intra-individual comparison of all treatments
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Microarray patch A<br>21 day treatment, once weekly, 3 applications in total, transdermal patch for cutaneous use | Drug: Microarray patch A<br>* Microarray patch<br>* Other names: Betamethasone dipropionate;|
| Experimental: Microarray patch B<br>21 day treatment, 3 times weekly, 9 applications in total, transdermal patch for cutaneous use | Drug: Microarray patch B<br>* Microarray patch<br>* Other names: Betamethasone dipropionate;|
| Placebo Comparator: Vehicle<br>21 day treatment, once weekly, 3 applications in total, transdermal patch for cutaneous use, no active substance | Drug: Placebo<br>* Microarray patch vehicle<br>|
| Active Comparator: Daivobet<br>21 day treatment, paused on day 7, day 14 and day 21, Cutaneous use | Drug: Daivobet<br>* Daivobet Gel<br>* Other names: Betamethasone dipropionate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall number of treatment-emergent adverse events. |  | First IMP application up to trial end (Day 50) | 
| Number of treatment-emergent application site reactions, by treatment |  | First IMP application up to trial end (Day 50) | 
| Change from baseline to Day 22 (EoT) in haematology parameters. | RBC, WBC, haemoglobin, haematocrit, platelets, white cell differentials; measured in SI units. | From baseline up to EoT (Day 22) | 
| Change from baseline to Day 22 (EoT) in clinical chemistry parameters. | Sodium, potassium, BUN, glucose, AST, ALT, gamma GT, AP, calcium, phosphate, albumin, total cholesterol, LDH, total protein, creatinine, total bilirubin; measured in SI units. | From baseline to EoT (Day 22) | 
| Change from baseline to Day 22 (EoT) in urinalysis parameters, single parameters only to be listed if deviation from usual urine dip test. | E.g., leukocytes, nitrite, pH, protein, glucose, ketones, urobilinogen, bilirubin, blood/haemoglobin, measured in SI units. | From baseline to EoT (Day 22) | 
| Number of subjects with abnormal clinically significant findings of physical examination at Day 22 (EoT). | Evaluation of physical examination (areas skin, heart, lung, abdomen, basic neurological status, general examination of eyes, ears, nose, throat), overall evaluation, assessed by investigator as 'normal', 'abnormal not clinically significant', 'abnormal clinically significant'. | EoT (Day 22) | 
| Change from baseline to Day 22 (EoT) in systolic and diastolic blood pressure. | Measured in mmHg. | From baseline to EoT (Day 22) | 
| Change from baseline to Day 22 (EoT) in pulse. | Measured in beats per minute. | From baseline to EoT (Day 22) | 
| Frequency counts of overall tolerability assessment of skin reactions at Day 8, Day 15, Day 22, Day 36 and Day 50. | (Assessment performed by an investigator using a 4-point score ['0 = very good', '1 = good', '2 = moderate', '3 = poor']). | From baseline up to trial end (Day 50) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline (pre-dose at Day 1) to Day 22 (EoT) in psoriatic infiltrate thickness. | (Assessed by measurement of the thickness of the Echo Poor Band [EPB] of the inflammatory infiltrate using 22-MHz sonography; measured in µm). | EoT (Day 22) |