Investigation of the Efficacy of 2.5% and 5% Cis-urocanic Acid in Patients With Moderate or Severe Atopic Dermatitis

Study Overview
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Brief Summary
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The purpose of this study is to evaluate dose response, safety, tolerability and efficacy of 2.5% and 5% cis-UCA in comparison to placebo and active comparator in the treatment of adult patients with moderate or severe chronic atopic dermatitis.

Detailed Description
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This is a Phase II multi-centre, double-blinded, vehicle-controlled, repeated and multiple dose, study to evaluate dose response, safety, tolerability and efficacy of 2.5% and 5% cis-UCA compared to placebo, and investigator-blinded to compare the safety, tolerability and efficacy of cis-UCA to the active comparator Protopic® 0.1% in patients with moderate or severe chronic atopic dermatitis treated for up to 28 days. The primary objective is to compare the efficacy of two different doses of cis-UCA (2.5% and 5%) with placebo for up to 28 days in adult patients with moderate or severe chronic atopic dermatitis to determine the dose of cis-UCA for further clinical development. Secondary objectives are as follows: To evaluate safety and tolerability of cis-UCA after topical twice daily doses of 2.5% and 5% for up to 28 days in adult patients with moderate or severe chronic atopic dermatitis. To evaluate dose response after topical twice daily doses of 2.5% and 5% for up to 28 days in adult subjects with moderate or severe chronic atopic dermatitis. To compare the efficacy and safety of 2.5% and 5% of cis-UCA to the efficacy and safety of 0.1% Protopic® after topical twice daily doses for up to 28 days in adult patients with moderate or severe chronic atopic dermatitis The key eligibility criteria are the following: patients with moderate or severe chronic atopic dermatitis, at least 18 years of age, with no current treatment for atopic dermatitis with active systemic medication or active topical treatment in the planned investigational area, and with no history of any significant disease that would affect the use of cis-UCA or comparator. In total, up to 150 adult patients (both males and females; at least 20% of each gender) with moderate or severe chronic atopic dermatitis will be included in the study. Up to 36 adult patients (both males and females) will be included in each treatment arm.

Official Title
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Phase II Study to Investigate the Properties of Topical Twice Daily Doses of 2.5% and 5% Cis-urocanic Acid in Comparison to Active Comparator 0.1% Protopic® for up to 28 Days in Patients With Moderate or Severe Atopic Dermatitis

Conditions
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Atopic Dermatitis

Intervention / Treatment
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* Drug: Cis-UCA 2.5% emulsion cream
* Drug: Cis-UCA 5% emulsion cream
* Drug: Placebo for cis-UCA emulsion cream
* Drug: Protopic® 0.1% ointment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent obtained prior to any screening procedure Caucasian male or female patient At least 18 years of age Weight at least 45 kg Patient with moderate or severe chronic atopic dermatitis Good general health ascertained by medical history, physical examination and laboratory determinations, showing no signs of clinically significant findings, except chronic atopic dermatitis Negative pregnancy test (premenopausal female patient) at screening and use of adequate contraceptive measures (both male and female patients) throughout the study and 30 days after the last cis-UCA dose Exclusion Criteria: History of other significant skin disease, or skin manifestations of allergic illness or other dermatologic condition, except chronic moderate or severe atopic dermatitis, that would interfere with the trial assessments or compromise the patient's safety according to the opinion of the Investigator Present symptoms of other skin diseases, except chronic atopic dermatitis, that could disturb the study assessment and evaluation of the skin Current use of any active systemic medication for chronic atopic dermatitis within one month Current use of active topical medication in the planned investigational area for chronic atopic dermatitis within two weeks History of a sunny holiday, UV-light therapy or solarium use within one month before beginning of study treatments, or planning such during the study or within 7 days after the study Allergy to cis-UCA, or any constituents of the placebo emulsion cream or any constituents of Protopic® ointment History of any skin-related cancer Congenital or acquired immunodeficiency or ongoing therapy that cause immunosuppression Earlier participation in a clinical study performed with cis-UCA Any clinically significant laboratory test result Suspected current drug or alcohol abuse Clinically significant illness during the 4 weeks prior to the first dose administration Any other condition that in the opinion of the Investigator would interfere with the evaluation of the study results or constitute a health hazard for the patient Unwillingness or doubtful capacity to comply with the protocol Doubtful availability to complete the study

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 2 Cis-UCA 5% emulsion cream<br> | Drug: Cis-UCA 5% emulsion cream<br>* 5% cis-UCA in emulsion cream base twice daily, amount of a fingertip per one hand (i.e. palm + thumb + fingers) area, applied topically as a thin layer on the affected skin area of approximate size of maximally three hand areas for up to 28 days (one fingertip per one hand area)<br>* Other names: Cis-UCA 5%;|
| Placebo Comparator: Group 3 Placebo cis-UCA emulsion cream<br> | Drug: Placebo for cis-UCA emulsion cream<br>* The placebo for cis-UCA product (emulsion cream base) twice daily, amount of a fingertip per one hand area applied topically as a thin layer on the affected skin area on of approximate size of maximally three hand areas for up to 28 days (one fingertip per one hand area).<br>* Other names: Placebo;|
| Active Comparator: Group 4 Protopic® 0.1% ointment<br> | Drug: Protopic® 0.1% ointment<br>* 0.1% Protopic® twice daily, amount of a fingertip per one hand area applied topically as a thin layer on the affected skin area of approximate size of maximally three hand areas for up to 28 days (one fingertip per one hand area).<br>* Other names: Protopic®;|
| Experimental: Group 1 Cis-UCA 2.5% emulsion cream<br> | Drug: Cis-UCA 2.5% emulsion cream<br>* 2.5% cis-UCA in emulsion cream base twice daily, amount of a fingertip per one hand (i.e. palm + thumb + fingers) area, applied topically as a thin layer on the affected skin area of approximate size of maximally three hand areas for up to 28 days (one fingertip per one hand area)<br>* Other names: Cis-UCA 2.5%;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Skin Assessment of erythema, oedema/papulation, oozing/crusts, excoriations, and lichenification |  | 37 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Skin Erythema measurement |  | 37 days | 
| Transepidermal Water Loss (TEWL) measurement |  | 37 days | 
| Visual Analogue Scale (VAS) assessment for itching (pruritus) of the treatment area |  | 37 days | 
| Physician Global Assessment (PGA) |  | 37 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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atopic dermatitis, cis-urocanic acid