Phase I, Randomized, double-blind, vehicle-controlled study to evaluate the safety, tolerability, PK and efficacy of M528101 in Healthy Volunteers and AD subjects

Completed

• Conditions: Atopic Dermatitis; Eczema; 10014982

• Registration Number: NL-OMON50835
• Lead Sponsor: Maruho Co,Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 2023-03-31
• Last Update Posted: 11 June 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 36

Inclusion Criteria

Part A
Subjects who meet all of the following criteria are eligible to participate in
this study:
1. Healthy male subjects, 18 to 45 years of age, inclusive. Healthy status is
defined by absence of evidence of any active or chronic disease following a
detailed medical and surgical history, a complete physical examination
including vital signs, 12-lead ECG, hematology, blood chemistry, blood serology
and urinalysis;
3. Body mass index (BMI) between 18 and 30 kg/m2, inclusive, and with a minimum
weight of 50 kg;
3. Subjects must use effective contraception for the duration of the study;
4. Able and willing to give written informed consent and to comply with the
study restrictions;
5. Subject has a negative result of COVID-19 test at Day -1.

Part B and C
1. Male subjects with mild to moderate AD (IGA 2 or 3) 18 to 65 years of age,
inclusive; Healthy status is defined by absence of evidence of any active or
chronic disease except for atopic dermatitis following a detailed medical and
surgical history, a complete physical examination including vital signs,
12-lead ECG, hematology, blood chemistry, blood serology and urinalysis;
2. Diagnosed with AD according to the Hanifin & Rajka criteria;
3. Body mass index (BMI )>=18 kg/m2, with a minimum of 50 kg;
4. Subjects must use effective contraception for the duration of the study;
5. Suitable target lesions defined as eczema lesions of 3- 10% BSA (excluding
the head, face and genitals)
In part C, the first 6 subjects have eczema lesions with 3 to 5% BSA and 3
subjects have 8 to 10% BSA;
6. Subject has a negative result of COVID-19 test at Day -1;
7. Average Pruritus (AP) NRS *3 at Screening and AP NRS*5 at Day1. The AP NRS
score for each visits will be determined by a single AP NRS assessment
(ranging from 0 to 10) of the past 24-hours.

Inclusion Criteria Part C only
8. Average of daily AP NRS*5 at Day 1 The average of daily AP NRS score will be
determined based on the average of Daily AP NRS scores (score ranging from 0 to
10) of the past three days.

Exclusion Criteria

Exclusion Criteria part A
1. Any disease associated with immune system impairment, including auto-immune
diseases, allergies, HIV and transplantation patients;
2. History of pathological scar formation (keloid, hypertrophic scar);
3. Excessive sun exposure or a tanning booth within 21 days prior to Day 1;
4. Participation in an investigational drug or device study within 3 months
prior to screening or more than 4 times a year;
5. Loss or donation of blood over 500 mL within three months prior to
screening. Or the donation of plasma within 14 days prior to screening;
6. Current smoker and/or regular user, of other nicotine-containing products
(e.g., patches). Regular users are defined as someone who smokes more than 10
cigarettes per day;
7. History of or current drug or substance abuse considered significant by the
PI (or medically qualified designee), including a positive urine drug screen;
8. Subject has a body temperature of >38.0 °C at screening and/or Day 1;
9. Have known history of atopy;
10. No prescription medications and OTC medications will be permitted within 21
days prior to study drug administrations, or less than 5 half-lives (whichever
is longer, and during the course of the study;
11. Have any current and / or recurrent pathologically, clinically significant
skin condition at the treatment area (i.e. atopic dermatitis).

Exclusion Criteria part B and C
1. Any disease associated with immune system impairment, including auto-immune
diseases, allergies, HIV and transplantation patients;
2. History of pathological scar formation (keloid, hypertrophic scar);
3. Excessive sun exposure or a tanning booth within 21 days prior to Day 1;
4. Participation in an investigational drug or device study within 3 months
prior to screening or more than 4 times a year;
5. Loss or donation of blood over 500 mL within three months prior to
screening. Or the donation of plasma within 14 days prior to screening;
6. Current smoker and/or regular user of other nicotine-containing products
(e.g., patches). Regular users are defined as someone who smokes more than 10
cigarettes per day;
7. History of or current drug or substance abuse considered significant by the
PI (or medically qualified designee), including a positive urine drug screen;
8. Subject has a body temperature of >38.0 °C at screening and/or Day 1;
9. Any topical anti-AD drugs on the lesional sites within 7 days prior to Day
1, for all other systemic anti-AD drugs a washout period of 4 weeks or 5
half-lives (whichever is longer) is required, or planned to use during the
course of the study;
10. Requirement of immunosuppressive or immunomodulatory medication within 28
days or 5 half-lives (whichever is longer) prior to Day 1 or planned to use
during the course of the study;
11. Use of antihistamines within 14 days prior to start of the study (Day 1).

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Primary endpoints are safety, tolerability and PK after IMP is administered<br /><br>once a day in part A and B and three times a day for 14 days in Part C.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Pharmacodynamic endpoints<br /><br>• Change from baseline in EASI total score in part C.<br /><br>• Change from baseline in SCORAD total score and each component signs and<br /><br>symptoms of AD in part C (erythema, induration/papulation, exudation,<br /><br>excoriation, lichenification).<br /><br>• Change from baseline in treatable BSA in part C.<br /><br>• Change in NRS itch score (Peak pruritus NRS, average NRS) from Baseline to<br /><br>Day 14 for Part C.<br /><br>• Time course change in NRS itch score in Part B.<br /><br>• Time course change in NRS itch score (Daytime 12 hr itch and nighttime 12 hr<br /><br>itch) in Part C.<br /><br>• Change of nighttime duration of scratching in Part C.<br /><br>• Change in NRS sleeplessness in Part C.</p><br>