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

Sponsor

Neuracle Science Co., LTD. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05143463

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

4.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Neurodegenerative Diseases	Drug: NS101 IV infusion	Phase 1

Detailed 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.

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 & 6 only, one single CSF sample will be collected via lumbar puncture over the study, for PK and PD analysis.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

64 participants

Allocation:

Randomized

Intervention Model:

Sequential Assignment

Intervention 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.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 (Participant, Investigator)

Masking Description:

Subjects will be administered each treatment (NS101 or placebo), according to the block randomization scheme. The subjects and the clinical personnel involved in the collection, monitoring, revision, or evaluation of AEs, or personnel who could have an impact on the outcome of the study will be blinded with respect to the subject's treatment assignment (NS101 or placebo).

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Nov 4, 2021

Anticipated Primary Completion Date :

Aug 19, 2022

Anticipated Study Completion Date :

Feb 3, 2023

Arms and Interventions

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.

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

Outcome Measures

Primary Outcome Measures

AEs of NS101 following intravenous (IV) administration of single ascending doses in healthy subjects [up to 60 Days ± 3 after IV infusion]
To assess Incidence, nature, relatedness, and severity of adverse events (AEs) of NS101 following intravenous (IV) administration of single ascending doses in healthy subjects

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Yes

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

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Syneos Health	Québec		Canada

Sponsors and Collaborators

Neuracle Science Co., LTD.

Investigators

Principal Investigator: Richard Larouche, M.D., Syneos Health

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Neuracle Science Co., LTD.

ClinicalTrials.gov Identifier:

NCT05143463

Other Study ID Numbers:

NS101_P1_01

First Posted:

Dec 3, 2021

Last Update Posted:

May 13, 2022

Last Verified:

Nov 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Neurodegenerative Diseases

Study Results

No Results Posted as of May 13, 2022