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

Phase 2

Completed

Conditions: Psoriasis Vulgaris

Interventions: Drug: LEO 29102 Plus Betamethasone Dipropionate
Drug: Daivobet® Ointment
Drug: LEO 29102 Cream Vehicle
Drug: LEO 29102 cream
Drug: Betamethasone Dipropionate Cream
Drug: LEO 29102 Plus Calcipotriol Cream

Registration Number: NCT00875277

Lead Sponsor: LEO Pharma

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 24

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
LEO 29102 Plus Betamethasone Dipropionate	LEO 29102 Plus Betamethasone Dipropionate	LEO 29102 2.5 mg/g plus betamethasone 0.5 mg/g (as dipropionate) cream applied topically twice daily for 4 weeks.
Daivobet® Ointment	Daivobet® Ointment	Daivobet® ointment, combination of calcipotriol 50 mcg/g plus betamethasone 0.5 mg/g (as dipropionate) applied topically twice daily for 4 weeks.
LEO 29102 Cream Vehicle	LEO 29102 Cream Vehicle	LEO 29102 cream vehicle applied topically twice daily for 4 weeks.
LEO 29102 cream	LEO 29102 cream	LEO 29102 2.5 mg/g cream applied topically twice daily for 4 weeks
Betamethasone Dipropionate Cream	Betamethasone Dipropionate Cream	Betamethasone 0.5 mg/g (as dipropionate) cream applied topically twice daily for 4 weeks.
LEO 29102 Plus Calcipotriol Cream	LEO 29102 Plus Calcipotriol Cream	LEO 29102 2.5 mg/g plus calcipotriol 50mcg/g cream applied topically twice daily for 4 weeks.

Primary Outcome Measures

Name	Time	Method
Change in Total Clinical Score (TCS) of the Clinical Symptoms Compared to Baseline (Day 1)	From baseline (Day 1) to end of treatment (Day 29)	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).

Secondary Outcome Measures

Name	Time	Method
Change in Single Clinical Symptom Score: Erythema, Scaling, Infiltration Compared to Baseline	From baseline (Day 1) to end of treatment (Day 29)	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).
Pathology and Histology by Treatment: Epidermal Thickness	At end of 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. 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..
Change in Scaling Compared to Baseline	At Day 4, Day 8, Day 11, Day 15, Day 18, Day 22, and Day 25	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
Biomarkers by Immunochemistry: Epidermal Differentiation	At end of treatment	3 skin biopsies (punch biopsies of 3 mm) per participant were taken on Day 29 after the clinical scoring and ultrasound measurement.
Biomarkers by Immunochemistry: Epidermal Proliferation	At end of treatment	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.
Pathology and Histology by Treatment	At end of 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))
Change in Infiltration Compared to Baseline	At Day 4, Day 8, Day 11, Day 15, Day 18, Day 22, and Day 25	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
Ultrasonography: Change in Lesions Thickness From Baseline Measured by Ultrasound	At Day 8, Day 15, Day 22 and end of treatment	The lesion thickness was measured by ultrasound at baseline, Day 8, Day 15, Day 22 and end of treatment.
Change in Erythema Compared to Baseline	At Day 4, Day 8, Day 11, Day 15, Day 18, Day 22 and Day 25	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
Biomarkers by Immunochemistry	At end of treatment	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.
Pathology and Histology by Treatment: Frequency of Neutrophil Abscesses	At end of 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. 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.
Change in Total Clinical Score (TCS) of the Clinical Symptoms Compared to Baseline	At Day 4, Day 8, Day 11, Day 15, Day 18, Day 22, and Day 25	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).