A First-in-Human PoC Study With BEN2293 in Patients With Mild to Moderate Atopic Dermatitis

Overview

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.

Full Title of Study: “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

• Study Type: Interventional
• Study Design
  • Allocation: Randomized
  • Intervention Model: Parallel Assignment
  • Primary Purpose: Treatment
  • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Study Primary Completion Date: January 12, 2023

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.

Interventions

• Drug: BEN2293 (0.25% or 1.0% w/w) or matching placebo
  • BEN2293 and placebo will be administered as a topical ointment. Both ointments contain the same excipients; placebo ointment has been manufactured in the same way except for the addition of 0.25% and 1.0% (w/w) BEN2293.

Arms, Groups and Cohorts

• Experimental: Dose Regimen Low Dose
  • Low Dose Strength
• Experimental: Dose Regimen High Dose
  • High Dose Strength
• Placebo Comparator: Placebo
  • Placebo

Clinical Trial Outcome Measures

Primary Measures

• Safety and Tolerability – Local Tolerability
  • Time Frame: Up to 28 days
  • Assessment by means of prompted reporting of application site adverse events.

Secondary Measures

• PK-Cmax
  • Time Frame: Up to 28 days
  • The investigation of the plasma PK of BEN2293 and metabolite BEN6403 following multiple topical doses to mild to moderate AD patients.
• PK-AUC
  • Time Frame: Up to 28 days
  • The investigation of the plasma PK of BEN2293 and metabolite BEN6403 following multiple topical doses to mild to moderate AD patients.
• PK-Tmax
  • Time Frame: Up to 28 days
  • The investigation of the plasma PK of BEN2293 and metabolite BEN6403 following multiple topical doses to mild to moderate AD patients.
• PK-T1/2
  • Time Frame: Up to 28 days
  • The investigation of the plasma PK of BEN2293 and metabolite BEN6403 following multiple topical doses to mild to moderate AD patients.
• PK- Apparent terminal rate constant
  • Time Frame: Up to 28 days
  • The investigation of the plasma PK of BEN2293 and metabolite BEN6403 following multiple topical doses to mild to moderate AD patients.
• PK- Amount excreted over 24 hours
  • Time Frame: Up to 28 days
  • The investigation of the plasma PK of BEN2293 and metabolite BEN6403 following multiple topical doses to mild to moderate AD patients.
• PK- Fraction excreted over 24 hours
  • Time Frame: Up to 28 days
  • The investigation of the plasma PK of BEN2293 and metabolite BEN6403 following multiple topical doses to mild to moderate AD patients.
• PK- renal clearance
  • Time Frame: Up to 28 days
  • The investigation of the plasma PK of BEN2293 and metabolite BEN6403 following multiple topical doses to mild to moderate AD patients.
• Time to itch reduction
  • Time Frame: Up to 28 days
  • The investigation of the effect of BEN2293 on pruritus and Atopic Dermatitis in patients with mild to moderate AD.
• Fraction of patients achieving itch reduction
  • Time Frame: Up to 28 days
  • The investigation of the effect of BEN2293 on pruritus and Atopic Dermatitis in patients with mild to moderate AD.
• Change from baseline in the NRS for pruritus
  • Time Frame: Up to 28 days
  • The investigation of the effect of BEN2293 on pruritus and Atopic Dermatitis in patients with mild to moderate AD.
• Change from baseline in EASI score
  • Time Frame: Up to 28 days
  • The investigation of the effect of BEN2293 on pruritus and Atopic Dermatitis in patients with mild to moderate AD.
• Change from baseline in vIGA score
  • Time Frame: Up to 28 days
  • The investigation of the effect of BEN2293 on pruritus and Atopic Dermatitis in patients with mild to moderate AD.
• Change from baseline in EQ5D score
  • Time Frame: Up to 28 days
  • The investigation of the effect of BEN2293 on pruritus and Atopic Dermatitis in patients with mild to moderate AD.

Participating in This Clinical Trial

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. 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.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 65 Years

Are Healthy Volunteers Accepted: No

Investigator Details

• Lead Sponsor
  • BenevolentAI Bio
• Provider of Information About this Clinical Study
  • Sponsor
• Overall Official(s)
  • Pui Leung, MBChB FFPM, Principal Investigator, MAC Clinical Research