A Phase I Safety Study of NVG-291 in Healthy Adults

Study Overview
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Brief Summary
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This is a randomized, triple-blind (subjects, Investigators, and Sponsor blinded), placebo-controlled Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD) study to evaluate the safety and tolerability of NVG-291 administered by subcutaneous injection daily in healthy female participants. The trial is split into three parts, starting with Part 1 (SAD), then Part 2 (MAD - post-menopausal Females), and finally Part 3 (MAD - males and premenopausal females). In Part 1 (SAD), participants receive 1 dose on 1 day only and in Parts 2 and 3, participants receive 1 dose every day for 14 days.

Official Title
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A Randomized, Triple-Blind, Placebo-Controlled Phase I Study of Single and Multiple Ascending Doses of NVG-291 in Healthy Subjects

Conditions
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Spinal Cord Injury

Intervention / Treatment
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* Drug: NVG-291
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy subjects between 18 and 65 years old. BMI between 18 and 33 kg/m2, inclusive, and a total body weight > 50 kg. All laboratory values must be within normal limits or any abnormalities deemed not clinically significant. All subjects must be willing to abstain from sexual intercourse or to use adequate contraception during the study and for an additional 120 days after the follow-up visit. Subjects must not donate ova or sperm during the study and for an additional 120 days after the follow-up visit Subjects must be willing and able to comply with scheduled visits, all sample collections, and other trial procedures. Subjects must provide written informed consent. Exclusion Criteria: For premenopausal female subjects: Irregular menstrual cycles; Amenorrhea; or Abnormal vaginal bleeding A history (within the past year) or presence of a clinically significant infectious disease or hepatic, renal, gastrointestinal, cardiovascular, endocrine, respiratory, immunologic, hematologic, dermatologic, neurologic, or psychiatric abnormality. Blood pressure > 160/95 at screening or on Day -1. Any active or uncontrolled infections or other medical condition or circumstance that could interfere with the subject's participation in the study. History of allergic reaction to mannitol. Presence of a tattoo, piercing, scar, or other dermatologic abnormality at the injection site (abdomen), that might interfere with the ability to assess injection site reactions a significant history of atopic dermatitis as an adult, or history of severe allergic reaction to injections. INR > 1.4 or PTT > 50 or platelets <50x10^3/µL at screening or on Day -1. History of regular alcohol consumption exceeding 10 units/week (1 unit = 83 mL of 12% wine) within 6 months of screening. Test positive for use of drugs or alcohol at screening. Positive hepatitis B, hepatitis C, or HIV test at screening. Blood or plasma donation within 1 week prior to Day -1. Receipt of an investigational drug within 30 days or five half-lives of the drug (whichever is longer) prior to Day -1. Prior participation in this trial. Female subjects who are breastfeeding or who have a positive pregnancy test at screening or Day -1. History of any condition that might impair the subject's ability to understand or to comply with the requirements of the study or to provide informed consent. Receipt of a COVID-19 vaccination within 3 weeks prior to Day -1 Subject is at risk of self-harm or harm to others as evidenced by past suicidal behavior or endorsing items 4 or 5 on the Columbia-Suicide Severity Rating Scale at screening

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

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
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NVG-291 SAD<br>Doses will begin at the lowest dose level in Cohort 1, increasing in dose with each subsequent cohort to the highest dose level in Cohort 6 or until a maximum tolerated dose (MTD) is reached. | Drug: NVG-291<br>* NVG-291 is a drug injected under the skin (subcutaneous).<br>Other: Placebo<br>* Salt water is being used as a placebo and will be injected under the skin (subcutaneous).<br>|
| Experimental: NVG-291 MAD<br>Participants will receive 1 dose daily for for 14 consecutive days. The maximum starting dose for MAD will be 2 dose levels lower than the maximum dose achieved during SAD. There will be a maximum of 3 dosing cohorts in Part 2. The maximum daily dose in Part 2 will not exceed the maximum daily dose tolerated in Part 1. | Drug: NVG-291<br>* NVG-291 is a drug injected under the skin (subcutaneous).<br>Other: Placebo<br>* Salt water is being used as a placebo and will be injected under the skin (subcutaneous).<br>|
| Experimental: NVG-291 MAD - Males and Premenopausal Females<br>Participants will receive 1 dose daily for for 14 consecutive days. The dose maximum daily dose in Part 3 will not exceed the maximum daily dose tolerated in either Part 1 or 2. | Drug: NVG-291<br>* NVG-291 is a drug injected under the skin (subcutaneous).<br>Other: Placebo<br>* Salt water is being used as a placebo and will be injected under the skin (subcutaneous).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events | number and frequency of adverse events | Assessed through 7 days following the last dose of study drug | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic analysis (plasma) | measure of concentration of drug in blood plasma | Assessed on Day 1 (SAD and MAD) and Day 14 (MAD only) | 
| Immunogenicity analysis | number of participants with confirmed and titer results for the presence of anti-drug antibodies | Assessed on Day 1 (SAD and MAD), Day 8 (SAD and MAD) and Day 21 (MAD only) |