Clinical trial NCT05143463: A FIH Study to Assess the Safety and Tolerability of NS Intravenous NS101 Infusion
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neurodegenerative Diseases
Lead sponsor: Neuracle Science Co., LTD.
Sponsor class: INDUSTRY
First posted: 2021-12-03
Enrollment: 64
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
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.
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: AEs of NS101 following intravenous (IV) administration of single ascending doses in healthy subjects
timeFrame: up to 60 Days ± 3 after IV infusion
Secondary outcomes:
measure: AUC of NS101 in serum
timeFrame: up to 1416 hours after IV infusion
measure: Cmax of NS101 in serum
timeFrame: up to 1416 hours after IV infusion
measure: Concentrations of FAM19A5 in Cerebrospinal fluid (CSF)
timeFrame: up to 336 hours after IV infusion
measure: The immunogenicity profile of NS101
timeFrame: up to 1416 hours after IV infusion
Other outcomes:
Locations:
city: Québec
country: Canada
facility: Syneos Health
Study officials:
affiliation: Syneos Health
name: Richard Larouche, M.D.
role: PRINCIPAL_INVESTIGATOR
References: