A Trial to Evaluate Pharmacokinetics, Immunogenicity, Safety, and Tolerability of LEO 138559 in Healthy Japanese Subjects

Study Overview
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Brief Summary
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This trial will investigate the pharmacokinetics, immunogenicity, safety, and tolerability of LEO 138559 in healthy Japanese subjects. The trial consists of a screening period of up to 4 weeks, a single treatment with either LEO 138559 or placebo, and 8 follow-up visits to Day 85. A total of 24 healthy subjects will be enrolled in 3 dose groups (n=8 per dose group) and randomized to either LEO 138559 or placebo in a ratio of 6:2.

Official Title
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A Phase 1, Single-center, Double-blind, Randomized, Placebo-controlled, Single Ascending Dose Trial to Evaluate Pharmacokinetics, Immunogenicity, Safety, and Tolerability of LEO 138559 in Healthy Japanese Subjects

Conditions
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Atopic Dermatitis

Intervention / Treatment
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* Drug: LEO 138559
* Drug: LEO 138559 Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Males and females between 18 to 65 years of age, inclusive, at the Screening visit Japanese subjects to be considered ethnic Japanese must: Be born in Japan with parents and grandparents (maternal and paternal) of Japanese descent Not have lived outside of Japan for more than 10 years at the time of Screening No significant change in lifestyle since leaving Japan, including diet. Body mass index (BMI) between 18.0 and 32.0 kg/m2, inclusive, at the Screening visit. Healthy, determined by pre-trial medical evaluation at Principal Investigator's discretion Exclusion Criteria Female subjects of childbearing potential who are not willing to use highly effective contraception. Subject has clinically significant history or evidence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, immunological, musculoskeletal, infectious, metabolic, hematologic, neurological, or psychiatric disorder(s) as determined by the Principal Investigator or designee. Subject has any surgical or medical condition that might significantly alter the absorption, distribution, metabolism, or excretion of any drug as determined by the Principal Investigator or designee. Clinically significant infection within 4 weeks prior to randomization that may compromise the safety of the subject in the trial or the integrity of the trial. This includes clinically significant infections (common cold is allowed [with negative SARS-CoV-2 PCR test]) that in the opinion of the Investigator or Sponsor's Medical Monitor may compromise the safety of the subject in the trial, interfere with evaluation of the IMP, or reduce the subject's ability to participate in the trial. History of any active skin infection within 1 week prior to Screening or randomization. Subject who has taken immunosuppressive/immunomodulating medication within 4 weeks prior to randomization, topical corticosteroids, topical calcineurin inhibitors within 2 weeks prior to randomization, or was treated with biologics within 5 half-lives (if known) or 12 weeks prior to randomization, whichever is longer. Subject has used over-the-counter (OTC) medications (including vitamins), or herbal remedies from 14 days prior to admission until the End-of-trial Visit. By exception, paracetamol/acetaminophen ≤ 2 g per day is permitted. History of chronic alcohol or drug abuse within 12 months prior to Screening, or any condition associated with poor compliance as judged by the Investigator. Heavy smoker (daily average >10 cigarettes) within the last three months prior to Screening. Subject is unwilling to avoid use of alcohol or alcohol-containing foods, medications, or beverages, within 36 hours prior to admission until discharge from the Clinical Unit. Female subjects are breastfeeding or female subjects with a positive serum pregnancy test at the Screening visit or urine pregnancy test at admission. Subject is unwilling to avoid consumption of coffee and caffeine-containing beverages within 48 hours prior to admission until discharge from the Clinical Unit. Subject is unable to abstain from smoking (or other nicotine use) from admission until discharge from the Clinical Unit. Subject scheduled to receive COVID-19 vaccination within 2 weeks before IMP administration. Less than 4 weeks after the second COVID-19 vaccination or booster (if on a single dose vaccination, it should be 4 weeks after). Live attenuated viral vaccine administration within 12 weeks before LEO 138559 or planned within three months after the last administration of LEO 138559.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LEO 138559 Dose 1<br>LEO 138559 will be administered subcutaneously up to 3 injections per dosing | Drug: LEO 138559<br>* LEO 138559 is an antibody given by injection just under the skin.<br>|
| Experimental: LEO 138559 Dose 2<br>LEO 138559 will be administered subcutaneously up to 3 injections per dosing | Drug: LEO 138559<br>* LEO 138559 is an antibody given by injection just under the skin.<br>|
| Experimental: LEO 138559 Dose 3<br>LEO 138559 will be administered subcutaneously up to 3 injections per dosing | Drug: LEO 138559<br>* LEO 138559 is an antibody given by injection just under the skin.<br>|
| Placebo Comparator: Placebo<br>LEO 138559 placebo will be administered subcutaneously up to 3 injections per dosing | Drug: LEO 138559 Placebo<br>* LEO 138559 placebo is given by injection just under the skin. LEO 138559 placebo contains the same excipients in the same concentration as LEO 138559, except the medical ingredient LEO 138559.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-last: the area under the concentration-time curve from pre-dose (time 0) to the time of the last quantifiable concentration | Pharmacokinetic endpoint to be determined from serum concentrations | From Day 1 to Day 85 | 
| AUC0-inf: area under the concentration-time curve from pre-dose (time 0) extrapolated to infinite time | Pharmacokinetic endpoint to be determined from serum concentrations | From Day 1 to Day 85 | 
| Cmax: maximum serum LEO 138559 concentration | Pharmacokinetic endpoint to be determined from serum concentrations | From Day 1 to Day 85 | 
| tmax: time of maximum serum LEO 138559 concentration | Pharmacokinetic endpoint to be determined from serum concentrations | From Day 1 to Day 85 | 
| t½: terminal elimination half-life | Pharmacokinetic endpoint to be determined from serum concentrations | From Day 1 to Day 85 | 
| CL/F: apparent total body clearance | Pharmacokinetic endpoint to be determined from serum concentrations | From Day 1 to Day 85 | 
| Vz/F: apparent volume of distribution | Pharmacokinetic endpoint to be determined from serum concentrations | From Day 1 to Day 85 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of treatment emergent adverse events |  | From Day 1 to Day 85 | 
| Presence of binding anti-drug antibodies |  | Day 1(pre-dose), Day 29, Day 57, and Day 85 |