Safety, Tolerability, Pharmacokinetics and Efficacy of WOL071-007 in Atopic Dermatitis Patients

NCT02576093 | Completed Phase 1 DMC

• 1 other identifier: KOR1-14/2013
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Dermatitis, Atopic

Outcome Measures

Primary Outcomes (3)

• Safety of WOL071-007 by recording adverse events (AEs) and other safety parameters over the Study Period

  Number of participants with AEs related to treatment and/or abnormal vital signs (blood pressure, pulse and temperature), monitored on each study day.

  SAD part: 2 days; MAD part: 7 days

• Local tolerability over the Study Period

  Number of participants with a change in at least one item of local tolerability scores (erythema, edema, vesiculation, oozing, scaling, cracking or crazing, scabbing, papules, reaction spreading outside area of application, glazing, burning or stinging), monitored on each study day.

  SAD part: 2 days; MAD part: 7 days

• Systemic Tolerability over the Study Period

  Number of participants with results from neurological examination other than normal (covering possible central and peripheral neurological disorders) and/or with abnormal safety laboratory values (standard hematology, blood chemistry), monitored on each study day.

  SAD part: 2 days; MAD part: 7 days

Secondary Outcomes (5)

• Maximum Plasma Concentration (Cmax) over the Treatment Period (MAD part only)

  6 days

• Change in Local Pruritus Intensity over the Study Period (MAD part only)

  7 days

• Change in Atopic Dermatitis Severity assessed by Eczema Area and Severity Index (EASI) over the Study Period (MAD part only)

  7 days

• Change in Atopic Dermatitis Severity assessed by IGADA scores over the Study Period (MAD part only)

  7 days

• Change in Atopic Dermatitis Severity assessed by local SCORAD over the Study Period (MAD part only)

  7 days

Study Arms (4)

0.1% WOL071-007

EXPERIMENTAL

Formulation containing 0.1% WOL071-007 for topical application

Drug: 0.1% WOL071-007

0.3% WOL071-007

EXPERIMENTAL

Formulation containing 0.3% WOL071-007 for topical application

Drug: 0.3% WOL071-007

1.0% WOL071-007

EXPERIMENTAL

Formulation containing 1.0% WOL071-007 for topical application

Drug: 1.0% WOL071-007

WOL071-007 Placebo

PLACEBO COMPARATOR

Formulation containing Placebo of WOL071-007 for topical application

Drug: Placebo of WOL071-007

Interventions

0.1% WOL071-007 DRUG

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.

0.1% WOL071-007

0.3% WOL071-007 DRUG

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.

0.3% WOL071-007

1.0% WOL071-007 DRUG

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.

1.0% WOL071-007

Placebo of WOL071-007 DRUG

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.

WOL071-007 Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent, including acceptance of biopsies.
• Male / female.
• Age between 18 and 75 years.
• Body weight between 60 and 130 kg for males and between50 and 110 kg for females. In addition the Body Mass Index (BMI) range limit of 19 - 32 kg/m² (both inclusive) is applicable.
• Lesional skin (at least 50 cm²) anywhere on the body (non-hairy skin) (SAD part only).
• Score of ≥40mm on all screening pruritus visual analogue scale (vas) assessments (average and worst over the last 24 hours and current itch) (MAD part only).
• Stable disease for ≥7 days prior to screening (MAD part only).
• Eczema on the right and left crook of the arms, or in the hollow of the knees (MAD part only).

You may not qualify if:

• Absence of written informed consent upon enrolment.
• Atopic dermatitis only affecting the head or scalp. Unstable or actively infected atopic dermatitis.
• Patients with severe atopic dermatitis (IGADA score \>2 or local SCORAD \>12).
• Concomitant dermatologic or medical condition(s) assessed by the investigator which may interfere with the investigator's ability to evaluate the patient's response to the study drug.
• Patients who have received monoclonal antibody therapy for their atopic dermatitis in the 4 months prior to the start of study treatment.
• Patients who have used systemic immunosuppressive drugs, corticosteroids or received puva therapy in the 4 weeks prior to starting study treatment, or are scheduled to start these treatments during the study period.
• Patients who have used topical immunomodulators (such as pimecrolimus, tacrolimus) within 1 week of starting study treatment or are scheduled to start these treatments during the study period.
• Patients who have used topical corticosteroids from who group II, III or IV, or other treatments for atopic dermatitis, including wet wraps, within 1 week prior to starting study treatment or are likely to require treatment with these medications during the study period of the SAD and MAD parts and from day 7 until day 14 of the MAD part.
• Patients who are unable to abstain from using emollients in the target imp (verum and placebo) assessment areas from day -3 until day 4 during the SAD part and from day -3 until day 14 during the MAD part.
• Patients who are using any concomitant medication(s), e.g. antihistamines, psychotropic drugs, immunosuppressive drugs, and immunologic drugs that, in the investigators' opinion, could affect the patient's atopic dermatitis or pruritus. Patients using such medications may be included, at the investigators discretion, if they have been stable on treatment for at least 1 month prior to the start of study treatment and no changes to these medications are planned during the study period.
• Patients undergoing ultraviolet A or B (UVA or UVB) therapy in the 2 weeks prior to starting study treatment or during the study period.
• Planned exposure of affected areas to excessive sunlight.
• Patients with any of the liver function tests (aspartate aminotransferase \[ast\], alanine aminotransferase \[alt\], alkaline phosphatase \[alp\], gamma-glutamyl-transferase \[ggt\]) \>2.0 x upper limit of normal, or with any clinically significant abnormal safety laboratory tests.
• Patients who are receiving any investigational drug or who have taken part in a clinical study with an investigational drug within three months prior to the start of study treatment.
• History of hypersensitivity and/or idiosyncrasy to any of the test compounds or excipients employed in this study.

Sponsors & Collaborators

• Dr. August Wolff GmbH & Co. KG Arzneimittel: lead
• Parexel: collaborator

Study Sites (1)

PAREXEL International GmbH Early Phase

Berlin, State of Berlin, 14050, Germany

Location

MeSH Terms

Conditions

Dermatitis, Atopic

Condition Hierarchy (Ancestors)

Skin Diseases, Genetic; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Dermatitis; Skin Diseases; Skin and Connective Tissue Diseases; Skin Diseases, Eczematous; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Study Officials

• Christoph Abels, MD

  Dr. August Wolff GmbH & Co. KG Arzneimittel

  STUDY DIRECTOR

• Georg Golor, MD

  Parexel GmbH

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 4, 2015
• First Posted: October 15, 2015
• Study Start: March 1, 2014
• Primary Completion: July 1, 2015
• Study Completion: July 1, 2015
• Last Updated: October 16, 2015

Record last verified: 2015-10

Locations

DE (1)