Clinical trial NCT04737304: A First-in-Human PoC Study With BEN2293 in Patients With Mild to Moderate Atopic Dermatitis
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Atopic Dermatitis
Lead sponsor: BenevolentAI Bio
Sponsor class: INDUSTRY
First posted: 2021-02-03
Enrollment: 123
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: 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.
timeFrame: Up to 28 days
Secondary outcomes:
measure: PK-Cmax
timeFrame: Up to 28 days
measure: PK-Tmax
timeFrame: Up to 28 days
measure: PK-T1/2
timeFrame: Up to 28 days
measure: PK-AUC
timeFrame: Up to 28 days
measure: PK- over a dosing interval (AUCт)
timeFrame: Up to 28 days
measure: PK - Accumulation ratio
timeFrame: Up to 28 days
measure: Time to itch reduction
timeFrame: Up to 28 days
measure: Fraction of patients achieving itch reduction
timeFrame: Up to 28 days
measure: Change from baseline in the Numerical Rating Scale (NRS) for pruritus - Worst Itch over 24 hours
timeFrame: Up to 28 days
measure: Change from baseline in the Numerical Rating Scale (NRS) for pruritus - Current Itch
timeFrame: Up to 28 days
measure: Change from baseline in Eczema Area and Severity Index (EASI) score
timeFrame: Up to 28 days
measure: Number of patients achieving improvement in Eczema Area and Severity Index (EASI) score
timeFrame: Up to 28 days
measure: Change from baseline in BSA affected by AD in treated area(s)
timeFrame: Up to 28 days
measure: Change from baseline in vIGA score
timeFrame: Up to 28 days
measure: Change from baseline in Patient Oriented Eczema Measure (POEM)
timeFrame: Up to 28 days
measure: Change from baseline in Dermatology Life Quality Index (DLQI)
timeFrame: Up to 28 days
measure: Change from baseline in EQ5D score
timeFrame: Up to 28 days
measure: Change from baseline in Patient Reported Outcomes Measurement Information System (PROMIS)
timeFrame: Up to 28 days
measure: Change from baseline in Insomnia Severity Index (ISI)
timeFrame: Up to 28 days
Other outcomes:
Locations:
city: Manchester
country: United Kingdom
facility: MAC Clinical Research
Study officials:
affiliation: MAC Clinical Research
name: Alexander Thompson, MBBS
role: PRINCIPAL_INVESTIGATOR
References: