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

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

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.

Study Overview

• Status: Completed
• Conditions: Neurodegenerative Diseases
• Intervention / Treatment: Drug: NS101 IV infusion

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Québec, Canada
    • Syneos Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. 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.

2. Healthy as defined by:

   1. the absence of clinically significant illness and surgery within 4 weeks prior to dosing.
   2. the absence of clinically significant history of neurological, endocrine, cardiovascular, respiratory, hematological, immunological, psychiatric, gastrointestinal, renal, hepatic, and metabolic disease.
3. Subject's score on the Sheehan Suicidality Tracking Scale (S-STS) at screening must be 0.

Exclusion Criteria:

1. 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.
2. Positive urine drug screen or alcohol breath test at screening or admission.
3. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sequential SAD - NS101; A staggered dosing schedule will be used for each dose level administered under fasting conditions.	Drug: NS101 IV infusion; 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.
Placebo Comparator: Sequential SAD - NS101 Placebo; Volume of matching placebo will be determined based on subject weight and NS101 concentration per cohort.	Drug: NS101 IV infusion; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Neuracle Science Co., LTD.
• Investigators: Principal Investigator: Richard Larouche, M.D., Syneos Health

Study record dates

Study Major Dates

• Study Start (Actual): November 4, 2021
• Primary Completion (Actual): August 19, 2022
• Study Completion (Actual): December 22, 2022

Study Registration Dates

• First Submitted: October 29, 2021
• First Submitted That Met QC Criteria: November 22, 2021
• First Posted (Actual): December 3, 2021

Study Record Updates

• Last Update Posted (Actual): December 23, 2022
• Last Update Submitted That Met QC Criteria: December 21, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neurodegenerative Diseases
• Other Study ID Numbers: NS101_P1_01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Will decide once CSR is released

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No