LEO 29102 Cream in the Treatment of Atopic Dermatitis

Study Overview
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Brief Summary
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This is a proof of concept and dose finding Phase II trial comparing 5 dose strengths with vehicle and an active comparator (Elidel cream 10 mg/g) in a 4 week, twice daily treatment regimen in mild to moderate atopic dermatitis patients.

Official Title
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A Phase 2, Proof of Concept and Dose Finding Study, Investigating Treatment Efficacy of LEO 29102 Cream, LEO 29102 Cream Vehicle, and Elidel® Cream 10 mg/g, After Cutaneous Administration Twice Daily for 4 Weeks

Conditions
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Atopic Dermatitis

Intervention / Treatment
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* Drug: LEO 29102
* Drug: Elidel®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of atopic dermatitis defined according to Hanifin and Rajka IGA assessment scored as mild (2) to moderate (3) atopic dermatitis Treatment lesions located on the trunk and limbs Treatment lesions involving 3% to 10% of the total body surface area Patients of either gender between 18 years and 65 years of age Exclusion Criteria: Systemic treatment with immunosuppressive drugs or corticosteroids within 6 weeks prior to randomisation Topical treatment with immunomodulators (pimecrolimus, tacrolimus) within 2 weeks prior to randomisation Topical treatment with corticosteroids from WHO groups II, III or IV within 1 week prior to randomisation Use of topical or systemic antibiotics within 2 weeks prior to randomisation PUVA or UVB therapy within 4 weeks prior to randomisation Clinical infection (viral, fungal or bacterial) on the treatment area Known or suspected severe renal insufficiency or severe hepatic disorders Patients with history of an immunocompromised disease (e.g., lymphoma, HIV, Wiskott-Aldrich Syndrome) Patients with concomitant serious disease (e.g., cancer) which might affect the AD treatment in this trial Females who are pregnant or are breast feeding Females intending to temporarily or permanently stop their hormonal contraceptive regime during and up to one month post study termination visit

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LEO 29102 0.03 mg/g cream<br> | Drug: LEO 29102<br>* comparison of different dosages of drug<br>|
| Experimental: LEO 29102 0.1 mg/g cream<br> | Drug: LEO 29102<br>* comparison of different dosages of drug<br>|
| Experimental: LEO 29102 0.3 mg/g cream<br> | Drug: LEO 29102<br>* comparison of different dosages of drug<br>|
| Experimental: LEO 29102 1.0 mg/g cream<br> | Drug: LEO 29102<br>* comparison of different dosages of drug<br>|
| Experimental: LEO 29102 2.5 mg/g cream<br> | Drug: LEO 29102<br>* comparison of different dosages of drug<br>|
| Placebo Comparator: LEO 29102 cream vehicle<br> | Drug: LEO 29102<br>* comparison of different dosages of drug<br>|
| Active Comparator: Elidel® cream (pimecrolimus) 10 mg/g<br> | Drug: Elidel®<br>* comparison<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Change in Eczema Area and Severity Index (EASI) Score From Baseline (Last Observation Carried Forward [LOCF]) | The EASI is a composite score based on the evaluation of four characteristic atopic dermatitis (AD) signs and symptoms; erythema, oedema/induration/papulation, excoriation and lichenification together with the area involved. For each body region, the investigator rated four clinical signs of AD using the following severity scale: 0 = none/absent = mild = moderate = severe The EASI score ranges from 0-12, a higher score equals a worse outcome. Baseline was defined as Day 0. Mean values in table are least squares mean adjusted for the effect of (pooled) country. | Baseline (Day 0) and end of treatment (Day 28) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants That Were Symptom Free Responders (LOCF) | The IGA (Investigator's global assessment) of disease severity on the body (trunk and limbs excluding the hands) was assessed based on visual evaluation by use of the following definitions of severity: 0. Clear - no inflammatory signs of AD Almost clear - just perceptible erythema, and just perceptible papulation/infiltration Mild - mild erythema, and mild papulation/infiltration Moderate - moderate erythema, and moderate papulation/infiltration Severe - severe erythema, and-severe papulation/infiltration Very severe - severe erythema, and severe papulation/infiltration with oozing/crusting. Symptom free responders were defined as an IGA of 0 (Clear) or 1 (Almost clear) at the end of treatment. | At end of treatment (Day 28) | 
| Participants' Assessment of Pruritus on Trunk and Limbs | Participants' assessment of pruritus on trunk and limbs was assessed at end of treatment by use of the scale below. Absent - no itching Mild - occasional, slight itching Moderate - constant or intermittent itching which is not disturbing sleep Severe - intolerable itching which is disturbing sleep The assessment was based on the average degree of pruritus over the last 24 hours. | At end of treatment (Day 28) | 
| Participants' Overall Assessment of Disease Severity | Participants' overall assessment of disease severity on trunk and limbs (excluding the hands) was assessed at end of treatment by use of the following scale: clear, very mild, mild, moderate, severe. The assessment was based on the condition of the disease at the time of the evaluation and not in relation to the condition at a previous visit. | At end of treatment (Day 28) | 
| Number of Participants That Were Symptom Free Responders by Visit | Symptom free responders were defined as an IGA of 0 (Clear) or 1 (Almost clear) according to Investigator's global assessment of disease severity on trunk and limbs at the end of treatment. | At Visit 2 (Day 7), Visit 3 (Day 14), Visit 4 (Day 21) and end of treatment (Day 28) | 
| Absolute Change in Eczema Area and Severity Index (EASI) Score From Baseline by Visit | The EASI is a composite score based on the evaluation of four characteristic atopic dermatitis (AD) signs and symptoms; erythema, oedema/induration/papulation, excoriation and lichenification together with the area involved. For each body region, the investigator rated four clinical signs of AD using the following severity scale: 0 = none/absent = mild = moderate = severe The EASI score ranges from 0-12, a higher score equals a worse outcome. Baseline was defined as Day 0. Mean values in table are least squares mean adjusted for the effect of (pooled) country. | Baseline and at Visit 2 (Day 7), Visit 3 (Day 14), Visit 4 (Day 21) |