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.
- Conditions
- Atopic DermatitisEczema10014982
- Registration Number
- NL-OMON51714
- Lead Sponsor
- BenevolentAI Bio Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 15
Patients meeting the following criteria will be included in the study:
1. 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.
2. Willing and able to comply with scheduled visits, treatment plan, laboratory
tests and other study procedures.
3. Patient is aged between 18 to 65 years, inclusive.
4. Patient has a body mass index (BMI) of 18.0 to 35.0 kg/m2, inclusive.
5. Body weight of >=50 kg.
6. History of AD for at least 6 months diagnosed by a dermatologist or GP.
7. Previous or current successful treatment with topical corticosteroids.
8. 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).
9. Atopic dermatitis affecting between >=1% to <=30% BSA of treatable skin (not
including face, scalp, genital area, palms of hands or soles of feet) at
Screening and Day -1 for all cohorts in Part A and at Screening, Day -3 and Day
1 for Part B.
10. History of AD associated pruritus with an itch score (NRS) of >=4.
· For Part A, the mean of the pruritus NRS scores (worst itch over the last 24
hours) obtained on Day -3, Day -2 and Day -1 during the emollient only washout
phase will be used to assess inclusion.
· For Part B, the mean of the pruritus NRS scores (worst itch over the last 24
hours) obtained on Day -5, Day -4 and Day -3 (pre-dose) during the emollient
only washout phase, and the mean of these scores on each day of the run-in
phase (Day -2, Day -1 and Day 1 [pre-dose]) will be used to assess
inclusion at Day -3 and Day 1, respectively. Where the run-in phase is extended
by 1 day, the mean NRS for all NRS scores reported over that time (minimum of
3) will be used to determine eligibility. Where patients are unable to provide
3 consecutive days of NRS scores for calculation of the average score to
determine eligibility, a minimum of 3 scores taken over a maximum of 4 days
will be used to calculate the average.
11. Patients must be willing to stop applying their daily emollients and
instead use the study emollient and shower cream from at least 7 days prior to
Day 1 in Part A and 10 days prior to Day 1 in Part B, and throughout their
participation in the study.
12. Males must use a condom during the trial and for 3 months after their final
dose study medication. In addition, their female partner of child-bearing
potential must be established on an additional method of highly effective
contraception (see Section 6.3.1) prior to dosing until 3 months following
final dosing.
13. Female patients of child-bearing potential must be established on a highly
effective method of contraception prior to dosing until 3 months after last
dose (see Section 6.3.1 for highly effective method of contraception) in
combination with male partner*s use of a condom during the trial and for 3
months after the last dose.
14. Female patients must have a negative pregnancy test at Screening and Day -1
(Part A only) and at Screening, Day -3 and Day 1 (Part B only).
15. Participant has a minimum of one AD area in a site suitable for biopsy.
16. Written informed consent, which includes
Patients with any of the following will be excluded from study participation:
1. 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.
2. Any skin tattoo, scar, cuts, bruises, or other skin damage, including
excessive UV exposure, at the possible IMP application sites.
3. Patients who have AD lesions affecting >3% untreatable areas (face, scalp,
genitals, palms of hands or soles of feet) (Cohorts 3 and 4 in Part A and Part
B only).
4. Patients who have a source of itch solely or significantly from untreatable
areas (face, scalp, genitals, palms of hands or soles of feet) (Cohorts 3 and 4
in Part A and Part B only).
5. 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.
6. Patients who are excessively hirsute in areas of skin to be dosed with study
ointment.
7. 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.
8. History of drug and/or alcohol abuse within the last 2 years, or intake of
>21 units of alcohol weekly, or a positive alcohol breath test at Screening or
Day -1 (Part A) and at Screening, Day -3 or Day 1 (Part B). One unit is
equivalent to a 285 mL glass of full-strength beer or one (30 mL) measure of
spirits or one small glass (100 mL) of wine.
9. Regular use of tobacco and/or nicotine containing products within 3 months
of Day 1, until the end of the study. Social smokers may be included in the
study as long as they are able to abstain from smoking/vaping during
residential stays (Part A only). Patients with a positive urine cotinine test
at Screening or Day -1 will not be eligible (Part A only). Use of tobacco
and/or nicotine containing products (up to 20 cigarettes per day, or
equivalent) is permitted for patients in Part B.
10. 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).
11. Positive urine test for drugs of abuse at Screening or Day -1 (Part A) and
at Screening or Day -3 (Part B).
12. Positive test for hepatitis B surface antigen (HBsAg), anti-hepatitis C
antibody (anti-HCV), human immunodeficiency virus I and II (anti-HIV I/II) or
SARS-CoV-2 at Screening.
13. Clinically relevant abnormal laboratory results (including hepatic and
renal panels, complete blood count, chemistry panel and urinalysis), 12-lead
ECG and vital signs, or physical findings at Screening or Day -1 (Part A) and
at Screening or Day -3 (Part B). In case of uncertain or questionable results,
tests performed during Screening, Day -1 or Day -3 may be repeated once to
confirm eligibility or judged to be clinically irrelevant.
14. Part B only: Patients treated within 28 days of Day 1 with tricyclic
antidepressants (e.g., amitriptyline), anticonvulsants (e.g., carbam
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary safety endpoints:<br /><br>· Adverse events, local tolerance assessments, vital signs, 12-lead ECG,<br /><br>laboratory safety tests (clinical chemistry, haematology and urinalysis).</p><br>
- Secondary Outcome Measures
Name Time Method