A Phase I Study to Assess the Safety, Tolerability and Pharmacokinetics of Single and Multiple Ascending Doses of NM-101 in Healthy Male and Female Subjects
Overview
- Phase
- Phase 1
- Intervention
- NM-101
- Conditions
- Parkinson Disease
- Sponsor
- Neuramedy Co. Ltd.
- Enrollment
- 56
- Locations
- 1
- Primary Endpoint
- Safety of NM-101: Incidence of Treatment-Related Adverse Events by Severity
- Status
- Not yet recruiting
- Last Updated
- 3 years ago
Overview
Brief Summary
This is a Phase I, double-blind, randomised, two-part, single-ascending dose (Part 1) and multiple-ascending dose (Part 2) study of NM-101 in healthy males and healthy females of non-childbearing potential
Detailed Description
NM-101 is an anti-TLR2 antibody which may have clinical efficacy in Parkinson's disease patients. This Phase I study aims to assess the safety, tolerability and pharmacokinetics (PK) of single and multiple ascending doses of NM-101 in healthy males and healthy females of non-childbearing potential. A total of 56 subjects (8 per cohort) are planned to be enrolled. Subjects will be randomly assigned to recieve NM-101 or placebo in a 3:1 ratio. The study will be in 2 parts: Part 1 will consist of 3 single-dose cohorts; Part 2 will consist of 4 multiple-dose cohorts. In Part 1, sentinel dosing will be applied. In each cohort, 1 subject will be randomised to receive NM-101 and 1 subject will be randomised to receive placebo ahead of dosing in the remaining 6 subjects. The dose for Cohort 1 is 20 mg/kg NN-101. The predicted doses for Cohorts 2 and 3 are 40 mg/kg and 60 mg/kg NM-101, respectively (dependent on a blinded interim review of the safety, tolerability and PK data). Blood samples will be collected at regular intervals for PK analysis and safety from Day 1 until Day 42. In Part 2, sentinel dosing will not be applied. Each subject will receive 4 doses of NM-101 or placebo over the course of 3 months. Dosing may occur in parallel to the conduct of Part 1. The doses administered will be selected based on emerging safety, tolerability and PK data from preceding groups in Part 1. The predicted NM-101 doses are: 10 mg/kg for Cohort 4; 20 mg/kg for Cohort 5; 40 mg/kg for Cohort 6; 60 mg/kg for Cohort 7. In Cohorts 5 to 7, subjects will undergo a lumbar puncture to assess NM-101 concentrations in the cerebrospinal fluid. Blood samples will be collected at regular intervals for PK analysis and safety from Day 1 until Day 127.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Informed Consent and Compliance
- •Must provide written informed consent
- •Must be willing and able to communicate and participate in the whole study
- •Demographics and Contraception
- •Aged 18 to 65 years inclusive at the time of signing informed consent
- •Must agree to adhere to the contraception requirements
- •Baseline Characteristics
- •Healthy males or WONCBP
- •Body mass index (BMI) of 18.0 to 32.0 kg/m2 as measured at screening
- •Must have received at least 2 doses of a COVID-19 vaccine
Exclusion Criteria
- •Medical/Surgical History and Mental Health
- •Serious adverse reaction or serious hypersensitivity to any drug or formulation excipients
- •History of allergic or anaphylactic reactions to humanised or other therapeutic monoclonal antibodies or to any of the excipients of NM-101
- •Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hay fever is allowed unless it is active
- •History of clinically significant cardiovascular, renal, hepatic, dermatological, chronic respiratory or gastrointestinal disease, neurological or psychiatric disorder, as judged by the investigator
- •Undergone a lumbar puncture within 6 weeks before Day 1 (Part 2 only)
- •Medical history or evidence of mass occupying lesion in brain or spinal cord or history of spinal cord injury, which could preclude the procedure of lumbar puncture and CSF collection (Part 2 only)
- •Evidence or history of clinically significant back pain, back pathology and/or back injury (e.g. degenerative disease, spinal deformity or spinal surgery) that may predispose to complications or technical difficulties in the conduct of a lumbar puncture (Part 2 only)
- •Physical Examination
- •Subjects who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator or delegate at screening
Arms & Interventions
NM-101
Ascending doses of NM-101. IV infusion over 2 hours
Intervention: NM-101
Placebo
IV infusion over 2 hours
Intervention: Placebo
Outcomes
Primary Outcomes
Safety of NM-101: Incidence of Treatment-Related Adverse Events by Severity
Time Frame: up to 4 months
A treatment related adverse event is defined as a clinical event with plausible time relationship to NM-101 administration and that cannot be explained by concurrent disease or other drugs or chemicals
PK Parameter
Time Frame: up to 4 months
Volume of distribution at steady state (Vss)
Secondary Outcomes
- Cerebrospinal Fluid (CSF) Concentrations of NM-101(Day 2 or Day 86)
- Immunogenicity of NM-101(up to 4 months)