A FIH Study to Assess the Safety and Tolerability of NS Intravenous NS101 Infusion

Study Overview
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Brief Summary
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Up to 80 healthy adult males, ≥ 18 and ≤ 55 years of age, are planned to be enrolled in the study. The study will consist of 8 cohorts (Cohorts 1 to 8, 1 cohort per dose level). Each cohort will include 8 subjects (6 subjects receiving a single dose of the study drug NS101 and 2 subjects receiving a single dose of a matching placebo), for a total of 64 subjects planned for evaluation. A total of 21 blood samples will be collected in each cohort for PK analysis and a total of 14 blood samples will be collected in each cohort for PD analysis.

Detailed Description
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The study will consist of 8 cohorts (Cohorts 1 to 8, 1 cohort per dose level). Each cohort will include 8 subjects (6 subjects receiving a single dose of the study drug NS101 and 2 subjects receiving a single dose of a matching placebo), for a total of 64 subjects planned for evaluation. For each dose level, the dose to be administered to each subject for a single infusion will be calculated based on subject's body weight, measured on Day 1. In each cohort, subjects will receive a single infusion of NS101 or matching placebo under fasting conditions over a period of approximately 60 minutes at the target dose level. A total of 21 blood samples will be collected in each cohort for PK analysis and a total of 14 blood samples will be collected in each cohort for PD analysis. A total of 6 immunogenicity blood samples will be collected for ADA and NAbs. For each subject in cohort 5 to 8 only, one single CSF sample will be collected via lumbar puncture over the study, for PK and PD analysis.

Official Title
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A Phase 1, Randomized, Placebo-controlled, Double-blind, Single Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Intravenous NS101 Infusion in Healthy Volunteers

Conditions
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Neurodegenerative Diseases

Intervention / Treatment
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* Drug: NS101 IV infusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male, non-smokers (no use of tobacco or nicotine products within 6 months prior to screening), ≥18 and ≤55 years of age, with BMI >18.5 and <30.0 kg/m2 and body weight ≥50.0 kg for males. Healthy as defined by: the absence of clinically significant illness and surgery within 4 weeks prior to dosing. the absence of clinically significant history of neurological, endocrine, cardiovascular, respiratory, hematological, immunological, psychiatric, gastrointestinal, renal, hepatic, and metabolic disease. Subject's score on the Sheehan Suicidality Tracking Scale (S-STS) at screening must be 0. Exclusion Criteria: Any clinically significant abnormality at physical examination, clinically significant abnormal laboratory test results or positive test for human immunodeficiency virus (HIV), hepatitis B, or hepatitis C found during medical screening. Positive urine drug screen or alcohol breath test at screening or admission. History of asthma, allergic rhinitis or urticaria, anaphylactic reactions, or any other clinically significant allergic reactions to any medication, including biologics, or food, or allergy to any excipient in the formulation.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

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: Sequential Assignment
Interventional Model Description: For each dose level, the dose to be administered to each subject for a single infusion will be calculated based on subject's body weight, measured on Day 1.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sequential SAD - NS101<br>A staggered dosing schedule will be used for each dose level administered under fasting conditions. | Drug: NS101 IV infusion<br>* Approximately 1 hour prior to start of study drug infusion, an IV port will be inserted into the antecubital region and a sterile normal saline solution infusion will be initiated at fixed rate in order to keep the vein open. The study drug will be infused over approximately 60 minutes at a constant rate. At the end of the infusion, 3 mL of saline solution will be injected to flush the remaining drug into the IV catheter. The end of infusion will be set to the end of the 3 mL flush. For safety reason (e.g., administration of rescue medication), the IV line will remain opened for approximately 1 hour following completion of infusion.<br>|
| Placebo Comparator: Sequential SAD - NS101 Placebo<br>Volume of matching placebo will be determined based on subject weight and NS101 concentration per cohort. | Drug: NS101 IV infusion<br>* Approximately 1 hour prior to start of study drug infusion, an IV port will be inserted into the antecubital region and a sterile normal saline solution infusion will be initiated at fixed rate in order to keep the vein open. The study drug will be infused over approximately 60 minutes at a constant rate. At the end of the infusion, 3 mL of saline solution will be injected to flush the remaining drug into the IV catheter. The end of infusion will be set to the end of the 3 mL flush. For safety reason (e.g., administration of rescue medication), the IV line will remain opened for approximately 1 hour following completion of infusion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AEs of NS101 following intravenous (IV) administration of single ascending doses in healthy subjects | To assess Incidence, nature, relatedness, and severity of adverse events (AEs) of NS101 following intravenous (IV) administration of single ascending doses in healthy subjects | up to 60 Days ± 3 after IV infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC of NS101 in serum | To characterize the pharmacokinetic (PK) profile of NS101 in serum following single IV infusion doses in healthy subjects | up to 1416 hours after IV infusion | 
| Cmax of NS101 in serum | To characterize the pharmacokinetic (PK) profile of NS101 in serum following single IV infusion doses in healthy subjects | up to 1416 hours after IV infusion | 
| Concentrations of FAM19A5 in Cerebrospinal fluid (CSF) | To investigate FAM19A5 concentrations in CSF following single IV infusion doses in healthy subjects for Cohort 5 to 8 only | up to 336 hours after IV infusion | 
| The immunogenicity profile of NS101 | To measure as the number and percentage of subjects who develop detectable Anti-Drug Antibody (ADA) and Neutralizing Antibody (NAb). | up to 1416 hours after IV infusion |