Safety, Tolerability, Pharmacokinetics and Efficacy of WOL071-007 in Atopic Dermatitis Patients
Condition: Dermatitis, Atopic
MeSH terms: Dermatitis, Atopic; Dermatitis
Study type: Interventional
Phase: Phase 1

Summary: 
      Purpose of the study is the local tolerability and systemic safety of a novel k-opioid
      receptor agonist proven to inhibit inflammation and pruritus in preclinical model of
      dermatitis.

      Three concentrations of WOL071-007 and placebo will be applied to patients with AD in a
      first-in-human, single-center, combined single/multiple ascending dose (SAD/MAD),
      double-blind, placebo-controlled, half-side comparison (MAD part only) study. The IMP will be
      applied occlusively to lesional or non-lesional skin. In the SAD part 24 subjects will
      receive the IMP for 2 days. In the MAD part, 30 hospitalized subjects will receive the IMP
      for 6 days. Study objectives are the safety and tolerability as well as (MAD part only) the
      pharmacokinetics and efficacy of WOL071-007.
    

Detailed description: 
      Three concentrations of the Investigational Medicinal Product (IMP) WOL071-007 (= active IMP)
      or placebo will be applied to patients with a clinical diagnosis of atopic dermatitis at
      screening with an Investigator's Global Dermatitis Assessment (IGADA) score of 1 or 2 (mild
      to moderate) and/or a local SCORing Atopic Dermatitis (SCORAD) ≤12.

      Each dose level cohort will begin with 2 sentinel patients: 1 patient randomized to receive
      active IMP and the other patient randomized to receive placebo only. From the remaining
      patients 1 patient will be randomized to receive placebo.

      In the Single Ascending Dose (SAD) part of the study the active IMP or placebo will be
      applied to a defined surface area of ≤ 100 cm² of non-lesional skin (Day 1) or lesional skin
      (Day 2) for about 22 hours and the patients will remain in the study center for at least 6
      hours after dosing.

      In the Multiple Ascending Dose (MAD) part placebo or test product + placebo (half-side
      comparison) will be administered up to 24 hours to achieve a defined surface area of
      approximately 2000 cm² in total (10% Body Surface Area) for each dose level cohort. A Data
      Safety Monitoring Board will review the data and recommend continuation following each dose
      level cohort.

      Primary criteria for evaluation are safety assessments, e.g. by Adverse Event (AE) recording,
      and assessments of the local tolerability (by scoring of local symptoms) as well as of the
      systemic tolerability (e.g. by blood tests and neurological examination) of WOL071-007. In
      the MAD part additionally pharmacokinetics will be measured and as secondary parameter local
      efficacy.
    

Intervention name(s): 0.1% WOL071-007; 0.3% WOL071-007; 1.0% WOL071-007; Placebo of WOL071-007
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): Application of approximately 2 mg cream/cm² skin to a defined surface area. SAD part: Single application to ≤ 100 cm² of non-lesional or lesional skin; MAD part: Multiple application (6 Days) to 2000 cm² of lesional and non-lesional skin.; Application of approximately 2 mg cream/cm² skin to a defined surface area. SAD part: Single application to ≤ 100 cm² of non-lesional or lesional skin; MAD part: Multiple application (6 Days) to 2000 cm² of lesional and non-lesional skin.; Application of approximately 2 mg cream/cm² skin to a defined surface area. SAD part: Single application to ≤ 100 cm² of non-lesional or lesional skin; MAD part: Multiple application (6 Days) to 2000 cm² of lesional and non-lesional skin.; Application of approximately 2 mg cream/cm² skin to a defined surface area. SAD part: Single application to ≤ 100 cm² of non-lesional or lesional skin; MAD part: Multiple application (6 Days) to 2000 cm² of lesional and non-lesional skin.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment