Clinical Trial to Assess Safety, Tolerability and the Pharmacodynamic Effect of Different Concentrations of a New Anti-inflammatory Substance in Subjects With Chronic Plaque Psoriasis

Study Overview
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Brief Summary
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To assess safety and tolerability after treatment with LEO 134310 cutaneous solution.

Official Title
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A Phase 1b, Randomised, Controlled, Observer-blinded Trial to Assess Safety, Tolerability and Pharmacodynamic Effects of LEO 134310 Cutaneous Solution in Descaled Skin of Adults With Chronic Plaque Psoriasis

Conditions
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Psoriasis Vulgaris

Intervention / Treatment
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* Drug: LEO 134310
* Drug: LEO 134310
* Drug: LEO 134310
* Drug: LEO 134310
* Drug: LEO 134310 vehicle
* Drug: 0.1% betamethasone valerate ointment (class III steroid)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects aged 18-64 years (inclusive) with plaque psoriasis in a chronic stable phase. Men or women of non-child bearing potential. Exclusion Criteria: Acute psoriasis guttata, psoriasis punctata, psoriasis erythrodermatica, pustular, exfoliative or inverse psoriasis. According to defined washout periods: topical antipsoriatic drugs (except salicylic acid in petroleum jelly); systemic antipsoriatics and biologics; ultraviolet (UV) therapy.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 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: Intra-individual comparison of all treatment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LEO 134310 Dose A<br>Once daily application | Drug: LEO 134310<br>* Active substance: LEO 134310 is a compound in development at LEO Pharma A/S<br>|
| Experimental: LEO 134310 Dose B<br>Once daily application | Drug: LEO 134310<br>* Active substance: LEO 134310 is a compound in development at LEO Pharma A/S<br>|
| Experimental: LEO 134310 Dose C<br>Once daily application | Drug: LEO 134310<br>* Active substance: LEO 134310 is a compound in development at LEO Pharma A/S<br>|
| Experimental: LEO 134310 Dose D<br>Once daily application | Drug: LEO 134310<br>* Active substance: LEO 134310 is a compound in development at LEO Pharma A/S<br>|
| Placebo Comparator: LEO 134310 vehicle<br>Once daily application | Drug: LEO 134310 vehicle<br>* Active substance: none<br>|
| Active Comparator: 0.1% betamethasone valerate ointment (class III steroid)<br>Once daily application | Drug: 0.1% betamethasone valerate ointment (class III steroid)<br>* Active substance: betamethasone valerate<br>|

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. |  | Up to Day 19 | 
| Number of treatment-emergent application site reactions, by treatment. |  | Up to Day 19 | 
| Change from baseline to Day 4, Day 8 and Day 12 in haematology parameters | red blood cells, white blood cells, hemoglobin, hematocrit, MCH, MMCV, MCHC, platelets, white cell differentials, measure in SI units | Up to Day 12 | 
| Change from baseline to Day 4, Day 8 and Day 12 in clinical chemistry parameters | sodium, potassium, chloride, bicarbonate, blood urea nitrogen, glucose, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gammaGT, uric acid, calcium, phosphate, albumin, triglycerides, cholesterol, lactate dehydrogenase, total protein, creatinine, total bilirubin, direct bilirubin, indirect bilirubin | Up to Day 12 | 
| Change from baseline to Day 4, Day 8 and Day 12 in urinalysis parameters | Single parameters only to be listed if deviation from usual urine dip test, e.g., sediment, leucocytes, nitrite, pH, protein, glucose, ketones, urobilinogen, bilirubin, blood/haemoglobin | Up to Day 12 | 
| Number of subjects with abnormal clinical significant ECG evaluation | Evaluation of 12-lead ECG (overall evaluation, assessed by investigator as 'normal', 'abnormal not clinically significant', 'abnormal clinically significant') | Up to Day 12 | 
| Number of subjects with abnormal clinically significant findings of physical examination at Day 12. | 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' | Up to Day 12 | 
| Change from baseline to Day 4, Day 8, Day 12 in systolic and diastolic blood pressure. | measured in mmHg | Up to Day 12 | 
| Change from baseline to Day 4, Day 8 and Day 12 in pulse. | measured in beats per minute | Up to Day 12 | 
| Change from baseline to Day 4, Day 8 and Day 12 in oral body temperature. | measured in degrees celsius | Up to Day 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline to Day 4, Day 8 and Day 12 in psoriatic infiltrate thickness (assessed by measurement of the thickness of the Echo Poor Band [EPB] of the inflammatory infiltrate using 22-MHz sonography) |  | 12 days | 
| Change from baseline to Day 12 in disease severity | Clinical assessment of change in disease severity (a global assessment performed by an investigator using a 5-point score ('-1 = worsened', '0 = unchanged', '1 = slight improvement', '2 = clear improvement but not completely healed', '3 = completely healed') | 12 days |