A Psoriasis Plaque Test With LEO 29102 Cream and Its Combination Products

Study Overview
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Brief Summary
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The purpose of this trial is to evaluate the anti-psoriatic effect of LEO 29102 cream and its combination with calcipotriol and betamethasone using a psoriasis plaque test method.

Official Title
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A Psoriasis Plaque Test Comparing LEO 29102 Cream and Its Different Combinations to Daivobet® Ointment and a Vehicle Control for the Treatment of Psoriasis Vulgaris

Conditions
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Psoriasis Vulgaris

Intervention / Treatment
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* Drug: LEO 29102 cream
* Drug: LEO 29102 Cream Vehicle
* Drug: Betamethasone Dipropionate Cream
* Drug: LEO 29102 Plus Calcipotriol Cream
* Drug: LEO 29102 Plus Betamethasone Dipropionate
* Drug: Daivobet® Ointment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: (in summary) Subjects having understood and signed an informed consent form All skin types Subjects with a diagnosis of psoriasis vulgaris with lesions located on arms, legs or trunk. The lesions must have a total size suitable for application. The subjects should be asked if their lesions have been stable Subjects willing and able to follow all the study procedures and complete the whole study Subjects affiliated to social security system Exclusion Criteria: (in summary) Females who are pregnant, of child-bearing potential and who wish to become pregnant during the study, or who are breast feeding Subjects using biological therapies (marketed or not marketed) with a possible effect on psoriasis (e.g. alefacept, efalizumab, etanercept, infliximab, adalimumab) within 12 weeks prior to study drug administration Systemic treatments with all other therapies than biologicals, with a potential effect on psoriasis vulgaris (e.g., corticosteroids, vitamin D-analogues, retinoids, immunosuppressants) within the 4-week period prior to randomisation Subjects using one of the following topical drugs for the treatment of psoriasis within four (4) weeks prior to study drug administration: - Potent or very potent (WHO group III-IV) corticosteroids - PUVA or Grenz ray therapy Subjects using one of the following topical drugs for the treatment of psoriasis within two (2) weeks prior to study drug administration: - WHO group I-II corticosteroids - Topical retinoids - Vitamin D-analogues - Topical immunomodulators (e.g. macrolides) - Anthracen derivatives - Tar - Salicylic acid - UVB therapy Subjects with skin manifestations in relation to syphilis or tuberculosis, rosacea, perioral dermatitis, acne vulgaris, atrophic skin, striae atrophicae, fragility of skin veins, ichthyosis, acne rosacea, ulcers and wounds within the plaque test areas

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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LEO 29102 cream<br>LEO 29102 2.5 mg/g cream applied topically twice daily for 4 weeks | Drug: LEO 29102 cream<br> <br> |
| Placebo Comparator: LEO 29102 Cream Vehicle<br>LEO 29102 cream vehicle applied topically twice daily for 4 weeks. | Drug: LEO 29102 Cream Vehicle<br> <br> |
| Experimental: Betamethasone Dipropionate Cream<br>Betamethasone 0.5 mg/g (as dipropionate) cream applied topically twice daily for 4 weeks. | Drug: Betamethasone Dipropionate Cream<br> <br> |
| Experimental: LEO 29102 Plus Calcipotriol Cream<br>LEO 29102 2.5 mg/g plus calcipotriol 50mcg/g cream applied topically twice daily for 4 weeks. | Drug: LEO 29102 Plus Calcipotriol Cream<br> <br> |
| Experimental: LEO 29102 Plus Betamethasone Dipropionate<br>LEO 29102 2.5 mg/g plus betamethasone 0.5 mg/g (as dipropionate) cream applied topically twice daily for 4 weeks. | Drug: LEO 29102 Plus Betamethasone Dipropionate<br> <br> |
| Active Comparator: Daivobet® Ointment<br>Daivobet® ointment, combination of calcipotriol 50 mcg/g plus betamethasone 0.5 mg/g (as dipropionate) applied topically twice daily for 4 weeks. | Drug: Daivobet® Ointment<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Total Clinical Score (TCS) of the Clinical Symptoms Compared to Baseline (Day 1) | The (sub)investigator made the following clinical assessments by use of the scale below: Score; Intensity; Description Erythema: 0; No evidence; Normal skin color 0.5; Doubtful or very mild 1.0; Mild; Pink light red 1.5; Mild to moderate 2.0; Moderate; Red 2.5; Moderate to severe 3.0; Severe; Intense red Scaling: 0; No evidence; No scaling 0.5; Doubtful or very mild 1.0; Mild; Slight roughness, mainly fine scales 1.5; Mild to moderate 2.0; Moderate; Coarse scaling 2.5; Moderate to severe 3.0; Severe; Coarse, thick scales Infiltration: 0; No evidence 0.5; Doubtful or very mild 1.0; Mild Slight definite infiltration 1.5; Mild to moderate 2.0; Moderate; Moderate infiltration 2.5; Moderate to severe 3.0; Severe; Very marked infiltration The TCS was defined as the sum of erythema plus scaling plus thickness scores. The TCS therefore ranged from 0 (all symptoms absent) to 9 (all symptoms severe). | From baseline (Day 1) to end of treatment (Day 29) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Single Clinical Symptom Score: Erythema, Scaling, Infiltration Compared to Baseline | The (sub)investigator made the following clinical assessments by use of the scale below: Score; Intensity; Description Erythema: 0; No evidence; Normal skin color 0.5; Doubtful or very mild 1.0; Mild; Pink light red 1.5; Mild to moderate 2.0; Moderate; Red 2.5; Moderate to severe 3.0; Severe; Intense red Scaling: 0; No evidence; No scaling 0.5; Doubtful or very mild 1.0; Mild; Slight roughness, mainly fine scales 1.5; Mild to moderate 2.0; Moderate; Coarse scaling 2.5; Moderate to severe 3.0; Severe; Coarse, thick scales Infiltration: 0; No evidence 0.5; Doubtful or very mild 1.0; Mild Slight definite infiltration 1.5; Mild to moderate 2.0; Moderate; Moderate infiltration 2.5; Moderate to severe 3.0; Severe; Very marked infiltration The TCS was defined as the sum of erythema plus scaling plus thickness scores. The TCS therefore ranged from 0 (all symptoms absent) to 9 (all symptoms severe). | From baseline (Day 1) to end of treatment (Day 29) | 
| Change in Erythema Compared to Baseline | The severity of the symptoms was rated on screening and on study Days 1 (baseline), 4, 8, 11, 15, 18, 22, 25 and 29 (end of treatment) according to the 0-3 with half-point TCS grading scale. The (sub)investigator made the following clinical assessments by use of the scale below: Score; Intensity; Description Erythema: 0; No evidence; Normal skin color 0.5; Doubtful or very mild 1.0; Mild; Pink light red 1.5; Mild to moderate 2.0; Moderate; Red 2.5; Moderate to severe 3.0; Severe; Intense red | At Day 4, Day 8, Day 11, Day 15, Day 18, Day 22 and Day 25 | 
| Change in Scaling Compared to Baseline | The severity of the symptoms was rated on screening and on study Days 1 (baseline), 4, 8, 11, 15, 18, 22, 25 and 29 (end of treatment) according to the 0-3 with half-point TCS grading scale. The (sub)investigator made the following clinical assessments by use of the scale below: Score; Intensity; Description Scaling: 0; No evidence; No scaling 0.5; Doubtful or very mild 1.0; Mild; Slight roughness, mainly fine scales 1.5; Mild to moderate 2.0; Moderate; Coarse scaling 2.5; Moderate to severe 3.0; Severe; Coarse, thick scales | At Day 4, Day 8, Day 11, Day 15, Day 18, Day 22, and Day 25 | 
| Change in Infiltration Compared to Baseline | The severity of the symptoms was rated on screening and on study Days 1 (baseline), 4, 8, 11, 15, 18, 22, 25 and 29 (end of treatment) according to the 0-3 with half-point TCS grading scale. The (sub)investigator made the following clinical assessments by use of the scale below: Score; Intensity; Description Infiltration: 0; No evidence 0.5; Doubtful or very mild 1.0; Mild Slight definite infiltration 1.5; Mild to moderate 2.0; Moderate; Moderate infiltration 2.5; Moderate to severe 3.0; Severe; Very marked infiltration | At Day 4, Day 8, Day 11, Day 15, Day 18, Day 22, and Day 25 | 
| Change in Total Clinical Score (TCS) of the Clinical Symptoms Compared to Baseline | The (sub)investigator made the following clinical assessments by use of the scale below: Score; Intensity; Description Erythema: 0; No evidence; Normal skin color 0.5; Doubtful or very mild 1.0; Mild; Pink light red 1.5; Mild to moderate 2.0; Moderate; Red 2.5; Moderate to severe 3.0; Severe; Intense red Scaling: 0; No evidence; No scaling 0.5; Doubtful or very mild 1.0; Mild; Slight roughness, mainly fine scales 1.5; Mild to moderate 2.0; Moderate; Coarse scaling 2.5; Moderate to severe 3.0; Severe; Coarse, thick scales Infiltration: 0; No evidence 0.5; Doubtful or very mild 1.0; Mild Slight definite infiltration 1.5; Mild to moderate 2.0; Moderate; Moderate infiltration 2.5; Moderate to severe 3.0; Severe; Very marked infiltration The TCS was defined as the sum of erythema plus scaling plus thickness scores. The TCS therefore ranged from 0 (all symptoms absent) to 9 (all symptoms severe). | At Day 4, Day 8, Day 11, Day 15, Day 18, Day 22, and Day 25 | 
| Ultrasonography: Change in Lesions Thickness From Baseline Measured by Ultrasound | The lesion thickness was measured by ultrasound at baseline, Day 8, Day 15, Day 22 and end of treatment. | At Day 8, Day 15, Day 22 and end of treatment | 
| Biomarkers by Immunochemistry | 3 skin biopsies (punch biopsies of 3 mm) per participant were taken on Day 29 after the clinical scoring and ultrasound measurement. Cells counted per mm^2 were cells that were positive for the indicated biomarker. | At end of treatment | 
| Biomarkers by Immunochemistry: Epidermal Differentiation | 3 skin biopsies (punch biopsies of 3 mm) per participant were taken on Day 29 after the clinical scoring and ultrasound measurement. | At end of treatment | 
| Biomarkers by Immunochemistry: Epidermal Proliferation | 3 skin biopsies (punch biopsies of 3 mm) per participant were taken on Day 29 after the clinical scoring and ultrasound measurement. By measurement of the cell-cycle marker, Ki-67 protein, an evaluation of the degree of skin cell proliferation and thereby epidermal proliferation could be obtained. Cells counted per mm^2 were cells that were positive for the indicated biomarker. | At end of treatment | 
| Pathology and Histology by Treatment | Skin biopsies were taken on Day 29. The evaluation of immunohistochemical sections were performed on cross sections of the skin tissue. The same pathologist did all evaluations, and samples were masked to ensure a blind fashion study. The extent of the following parameters were measured in scored semi-quantitatively (semi) on blinded haematoxylin and eosin (HE) sections. Semi-quantitative scoring was categorized as No (0), mild (1), moderate (2), marked (3) or severe (4). In evaluating the morphology of epidermis (Stratum corneum and Stratum granulosum) the tissue was classified by the characteristics seen below: Morphology of epidermis Stratum corneum (semi (extent of)) Stratum granulosum (semi (extent of)) Parakeratosis (semi (extent of)) Infiltration of inflammatory cells (semi (extent of)) | At end of treatment | 
| Pathology and Histology by Treatment: Epidermal Thickness | Skin biopsies were taken on Day 29. The evaluation of immunohistochemical sections were performed on cross sections of the skin tissue. The same pathologist did all evaluations, and samples were masked to ensure a blind fashion study. In evaluating the morphology of epidermis (Stratum corneum and Stratum granulosum), the tissue was classified by the characteristic epidermal thickness. This was measured in the absolute number of µm measured on blinded haematoxylin and eosin (HE) sections.. | At end of treatment | 
| Pathology and Histology by Treatment: Frequency of Neutrophil Abscesses | Skin biopsies were taken on Day 29. The evaluation of immunohistochemical sections were performed on cross sections of the skin tissue. The same pathologist did all evaluations, and samples were masked to ensure a blind fashion study. In evaluating the morphology of epidermis (Stratum corneum and Stratum granulosum), the tissue was classified by the characteristic of frequency of neutrophil microabscesses (Monroe´s abscess). This was measured in absolute number of cells that were positive for the marker on blinded haematoxylin and eosin (HE) sections. | At end of treatment |