Investigating the Safety of LEO 158968 in Healthy Volunteers

Study Overview
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Brief Summary
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The purpose of this study is to investigate what side effects the new compound LEO 158968 might cause and how well it is tolerated when it is used by healthy participants. It will also investigate how quickly and to what extent LEO 158968 is distributed and eliminated from the body and if LEO 158968 causes the body to make antibodies. In the single ascending dose (SAD) cohorts, participants will receive escalating doses of LEO 158968 if the safety and tolerability results of the initial participants up to 48 hours (or 4 days for SC dosing) following dosing are acceptable to the Investigator. In the multiple ascending dose (MAD) cohorts, the dose of LEO 158968 will be determined based on results derived from the earlier SAD cohorts and additional preclinical data from a 5-week good laboratory practice (GLP) cynomolgus monkey toxicology study.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Single- And Multiple Ascending Dose Trial To Evaluate The Safety, Tolerability, And Pharmacokinetics Of Leo 158968 In Healthy Subjects

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: LEO 158968
* Drug: Placebo
* Drug: LEO 158968
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: 18 to 60 years, inclusive, at screening Sex: Male or female Body mass index: 18.0 kg/m^2 to 32.0 kg/m^2, inclusive, at screening Health status: In good health as judged by the Investigator based on medical history, physical examination, electrocardiogram (ECG), hematology, biochemistry, and urinalysis. Exclusion Criteria: A participant who meets any of the following exclusion criteria will not be eligible for inclusion in the study: Male participants sexually active with a woman of childbearing potential who are not willing to use a barrier method of contraception (eg, condom) from the time of first dose of investigational medicinal product (IMP) until 16 weeks after the last dose, in conjunction with this female partner using a highly effective form of contraception. Female participants who are pregnant, lactating, or planning to become pregnant during the time of the trial. Participants with any surgical or medical condition which might significantly alter the distribution, metabolism, or excretion of any drug. Positive polymerase chain reaction (PCR) test for coronavirus disease-19 (COVID-19) on Day -1, or contact with COVID-19 positive (or suspected) persons within 14 days prior to first dose. ECG with QT-interval corrected for heart rate (QTc) using Fridericia's formula (QTcF) >450 msec for men, >460 msec for women, confirmed by repeat measurement at screening. Treatment with any prescribed or nonprescribed systemic or topical medication within 7 days prior to the first dose of IMP (excluding paracetamol; including herbal remedies), unless, in the opinion of the Investigator and the Sponsor, the medication will not interfere with the trial procedures or compromise safety.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Basic Science
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LEO 158968 Single Ascending Dose (SAD) Cohorts<br>Participants will receive a single dose of LEO 158968 or matching placebo via an intravenous (IV) infusion or subcutaneous (SC) injection. The dose of LEO 158968 will be increased per cohort. | Drug: LEO 158968<br>* IV infusion or SC injection<br>Drug: Placebo<br>* IV infusion or SC injection<br>|
| Experimental: LEO 158968 Multiple Ascending Dose (MAD) Cohorts<br>Participants will receive 5 once weekly (QW) doses of LEO 158968 or matching placebo via a SC injection. | Drug: LEO 158968<br>* SC injection<br>Drug: Placebo<br>* SC injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Treatment-emergent Adverse Events (TEAEs) Reported for Each Participant | Any clinically significant changes from baseline in clinical laboratory parameters, vital signs including systolic and diastolic blood pressure, and abnormal clinically significant findings from physical examinations following first dose will be recorded as TEAEs. | Day 1 to Day 113 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Serum Concentration-time Curve from Time 0 to Infinity (AUC0-∞) of LEO 158968 |  | Day 1 to Day 85 | 
| Area Under the Serum Concentration-time Curve from 0 Hours to 168 Hours (AUC0-168h) of LEO 158968 |  | Day 1 to Day 85 | 
| Area Under the Serum Concentration-time Curve from t=0 to t (AUC0-t) of LEO 158968 | Where t corresponds to the last observed quantifiable concentration calculated by the linear up - logarithmic down trapezoidal rule. | Day 1 to Day 85 | 
| Serum Concentration Observed at 168 Hours Post-dose (C168h) of LEO 158968 |  | Day 1 to Day 85 | 
| Maximum Observed Serum Concentration (Cmax) of LEO 158968 |  | Day 1 to Day 85 | 
| Apparent Terminal Half-life (t1/2) of LEO 158968 |  | Day 1 to Day 85 | 
| Time of Last Quantifiable Concentration (tlast) of LEO 158968 |  | Day 1 to Day 85 | 
| Time of Cmax (tmax) of LEO 158968 |  | Day 1 to Day 85 | 
| Area Under the Serum Concentration-time Curve Over the Dosing Interval τ (ie, 168 hours) (AUCτ) of LEO 158968 |  | Day 1 to Day 113 | 
| AUC0-t of LEO 158968 |  | Day 1 to Day 113 | 
| Trough Serum Concentration Observed at the End of a Dosing Interval (168 hours post-dose) (Cτ) of LEO 158968 |  | Day 1 to Day 113 | 
| Cmax of LEO 158968 |  | Day 1 to Day 113 | 
| t1/2 of LEO 158968 |  | Day 1 to Day 113 | 
| tlast of LEO 158968 |  | Day 1 to Day 113 | 
| tmax of LEO 158968 |  | Day 1 to Day 113 | 
| Number of Participants with Antidrug Antibodies (ADA) |  | Day 1 to Day 113 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Healthy Volunteers, LEO 158968