Double-blind, placebo-controlled, multi-centre Phase II study to investigate dose response, safety, tolerability and efficacy 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

INTERVENTION: Product Name: Cis‐UCA 2.5% emulsion cream Product Code: No product code available Pharmaceutical Form: Cream CAS Number: 7699‐35‐6 Current Sponsor code: cis‐UCA Other descriptive name: cis‐urocanic acid Concentration unit: % percent Concentration type: equal Concentration number: 2.5‐ Pharmaceutical form of the placebo: Cream Route of administration of the placebo: Cutaneous use Trade Name: Protopic 0.1 % ointment Product Name: Protopic 0.1 % ointment Pharmaceutical Form: Ointment CAS Number: 109581‐93‐3 Other descriptive name: TACROLIMUS MONOHYDRATE Concentration unit: % percent Concentration type: equal Concentration number: 0.1‐ Product Name: Cis‐UCA 5 % emulsion cream Product Code: No product code available Pharmaceutical Form: Cream CAS Number: 7699‐35‐6 Current Sponsor code: Cis‐UCA Other descriptive name: cis‐urocanic acid Concentration unit: % percent Concentration type: equal Concentration number: 5‐ Pharmaceutical form of the placebo: Cream Route of administration of the placebo: Cutaneous use CONDITION: Chronic moderate or severe atopic dermatitis PRIMARY OUTCOME: Main Objective: ‐ 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 Primary end point(s): The efficacy will be evaluated after treatment with cis‐urocanic acid, placebo or comparator by Clinical Skin Assessment of erythema, oedema/papulation, oozing/crusts, excoriations, and lichenification at treatment area. Visual Analogue Scale assessment for itching (pruritus) of the treatment area will be also performed. In addition, the evaluation of the atopic eczema in the treatment area will be assessed by Physician Global Assessment, and measuring Skin Erythema and Transepidermal Water Loss at treatment area by specific non‐invasive devices. ; The safety and tolerabilityof cis‐urocanic acid will be evaluated by collecting adverse events. Secondary Objective: ‐ 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; INCLUSION CRITERIA: 1. Informed consent obtained prior to any screening procedure 2. Caucasian male or female patient 3. At least 18 years of age 4. Weight at least 45 kg 5. Patient with moderate or severe chronic atopic dermatitis 6. Good general health ascertained by medical history, physical examination and laboratory determinations, showing no signs of clinically significant findings, except chronic atopic dermatitis 7. 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 ‐ Premenopausal female patient should be either surgically sterile or using a reliable contraception method: intrauterine device (hormonal or non‐hormonal); oral combination pill or hormonal contraception patch; or two of the following: intra‐vaginal hormonal ring, oral contraceptive containing progestin only, spermicidal foam, condom, ster