A First-in-Human, Double-Blind, Randomised, Vehicle Controlled Phase I/II Proof of Concept Study to Investigate the Safety, Tolerability, Pharmacokinetics and Efficacy of BEN2293 in Patients With Mild to Moderate Atopic Dermatitis
Overview
- Phase
- Phase 1
- Intervention
- BEN2293 (0.25% or 1.0% w/w) or matching placebo
- Conditions
- Atopic Dermatitis
- Sponsor
- BenevolentAI Bio
- Enrollment
- 123
- Locations
- 1
- Primary Endpoint
- Safety and tolerability assessed by means of incidence of adverse events, incidence of adverse events at the local application site, mean vital signs, mean 12-lead ECG parameters and mean safety laboratory results.
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
A randomised, adaptive design, double-blind, placebo-controlled, first-in-human, two-part study to investigate the safety, tolerability, PK and preliminary efficacy of multiple topical doses of BEN2293 in patients with mild to moderate AD.
Detailed Description
This Protocol will be adaptive and designed to enable knowledge gained from the previous cohort to be applied to subsequent cohorts. Changes made will be within the boundaries of the adaptive elements with clear control mechanisms and guidance for staying within these boundaries. Part A is a randomised, double-blind, placebo-controlled, sequential group study to investigate ascending multiple topical doses of BEN2293 in patients with mild to moderate AD. Patients will participate in only one cohort. Part B is a randomised, double-blind, placebo-controlled, parallel group study to investigate up to two dose regimens of topical doses of BEN2293 administered for a maximum of 28 days in patients with mild to moderate AD.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Males and females with mild to moderate AD (based on vIGA) free from other clinically significant illness or disease that may adversely affect the safety of the patient or the integrity of the study as determined by medical history, physical examination, safety laboratory and other assessments.
- •History of AD for at least 6 months diagnosed by a dermatologist or GP.
- •Previous or current successful treatment with topical corticosteroids.
- •A vIGA score of 2 (mild) to 3 (moderate) at both Screening and Day -1 (Part A) and at Screening, Day-3 and Day 1 (Part B).
Exclusion Criteria
- •Atopic dermatitis of such severity that the patient could not comply with the demands of the study and/or the patient is not a suitable candidate for a placebo controlled study, as per Investigator's discretion.
- •Any skin tattoo, scar, cuts, bruises, or other skin damage, including excessive UV exposure, at the possible IMP application sites.
- •Patients who have AD lesions affecting \>3% untreatable areas (face, scalp, genitals, palms of hands or soles of feet).
- •Have concomitant skin disease or infection (e.g., acne, impetigo) or presence of skin comorbidities in the study area to be dosed that may interfere with study assessments.
- •Patients who are excessively hirsute in areas of skin to be dosed with study ointment.
- •Patients who are unwilling to stop hair removal by any means (including shaving, waxing or depilatory creams) to skin areas to be dosed with study ointment for 2 weeks prior to Day -1 and throughout the duration of the study.
- •Clinically relevant history of abnormal physical or mental health interfering with the study as determined by medical history and physical examinations as judged by the Investigator (including \[but not limited to\], neurological, psychiatric, endocrine, cardiovascular, gastrointestinal, hepatic, or renal disorder).
- •The patient has participated in a clinical study and has received a medication or a new chemical entity within 3 months prior to Day 1.
Arms & Interventions
Placebo
Placebo
Intervention: BEN2293 (0.25% or 1.0% w/w) or matching placebo
Dose Regimen Low Dose
Low Dose Strength
Intervention: BEN2293 (0.25% or 1.0% w/w) or matching placebo
Dose Regimen High Dose
High Dose Strength
Intervention: BEN2293 (0.25% or 1.0% w/w) or matching placebo
Outcomes
Primary Outcomes
Safety and tolerability assessed by means of incidence of adverse events, incidence of adverse events at the local application site, mean vital signs, mean 12-lead ECG parameters and mean safety laboratory results.
Time Frame: Up to 28 days
Parameters measured by prompted reporting of adverse events and scheduled safety assessments.
Secondary Outcomes
- PK-AUC(Up to 28 days)
- PK - Accumulation ratio(Up to 28 days)
- Change from baseline in the Numerical Rating Scale (NRS) for pruritus - Worst Itch over 24 hours(Up to 28 days)
- Change from baseline in Eczema Area and Severity Index (EASI) score(Up to 28 days)
- Change from baseline in Patient Reported Outcomes Measurement Information System (PROMIS)(Up to 28 days)
- Fraction of patients achieving itch reduction(Up to 28 days)
- Change from baseline in the Numerical Rating Scale (NRS) for pruritus - Current Itch(Up to 28 days)
- Change from baseline in EQ5D score(Up to 28 days)
- Number of patients achieving improvement in Eczema Area and Severity Index (EASI) score(Up to 28 days)
- Change from baseline in Patient Oriented Eczema Measure (POEM)(Up to 28 days)
- Change from baseline in Insomnia Severity Index (ISI)(Up to 28 days)
- PK-T1/2(Up to 28 days)
- Time to itch reduction(Up to 28 days)
- Change from baseline in Dermatology Life Quality Index (DLQI)(Up to 28 days)
- PK-Cmax(Up to 28 days)
- PK-Tmax(Up to 28 days)
- PK- over a dosing interval (AUCт)(Up to 28 days)
- Change from baseline in BSA affected by AD in treated area(s)(Up to 28 days)
- Change from baseline in vIGA score(Up to 28 days)