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

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

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.

Study Overview

• Status: Completed
• Conditions: Spinal Cord Injury
• Intervention / Treatment: Drug: NVG-291; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 74
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Cara Casseday; Phone Number: (604) 488-5421; Email: info@nervgen.com
• Study Contact Backup: Name: Steven Mulcahy; Phone Number: (604) 488-5421; Email: info@nervgen.com

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Nucleus Networks

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Healthy subjects between 18 and 65 years old.
2. BMI between 18 and 33 kg/m2, inclusive, and a total body weight > 50 kg.
3. All laboratory values must be within normal limits or any abnormalities deemed not clinically significant.
4. 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.
5. Subjects must not donate ova or sperm during the study and for an additional 120 days after the follow-up visit
6. Subjects must be willing and able to comply with scheduled visits, all sample collections, and other trial procedures.
7. Subjects must provide written informed consent.

Exclusion Criteria:

1. For premenopausal female subjects: Irregular menstrual cycles; Amenorrhea; or Abnormal vaginal bleeding
2. 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.
3. Blood pressure > 160/95 at screening or on Day -1.
4. Any active or uncontrolled infections or other medical condition or circumstance that could interfere with the subject's participation in the study.
5. History of allergic reaction to mannitol.
6. 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
7. a significant history of atopic dermatitis as an adult, or history of severe allergic reaction to injections.
8. INR > 1.4 or PTT > 50 or platelets <50x10^3/µL at screening or on Day -1.
9. History of regular alcohol consumption exceeding 10 units/week (1 unit = 83 mL of 12% wine) within 6 months of screening.
10. Test positive for use of drugs or alcohol at screening.
11. Positive hepatitis B, hepatitis C, or HIV test at screening.
12. Blood or plasma donation within 1 week prior to Day -1.
13. Receipt of an investigational drug within 30 days or five half-lives of the drug (whichever is longer) prior to Day -1.
14. Prior participation in this trial.
15. Female subjects who are breastfeeding or who have a positive pregnancy test at screening or Day -1.
16. 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.
17. Receipt of a COVID-19 vaccination within 3 weeks prior to Day -1
18. 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NVG-291 SAD; 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; NVG-291 is a drug injected under the skin (subcutaneous).; Other: Placebo; Salt water is being used as a placebo and will be injected under the skin (subcutaneous).
Experimental: NVG-291 MAD; 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; NVG-291 is a drug injected under the skin (subcutaneous).; Other: Placebo; Salt water is being used as a placebo and will be injected under the skin (subcutaneous).
Experimental: NVG-291 MAD - Males and Premenopausal Females; 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; NVG-291 is a drug injected under the skin (subcutaneous).; Other: Placebo; Salt water is being used as a placebo and will be injected under the skin (subcutaneous).

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: NervGen Pharma
• Investigators: Study Director: Daniel Miko, MD, CMO

Study record dates

Study Major Dates

• Study Start (Actual): May 6, 2021
• Primary Completion (Actual): June 4, 2023
• Study Completion (Actual): July 3, 2023

Study Registration Dates

• First Submitted: March 15, 2022
• First Submitted That Met QC Criteria: March 24, 2022
• First Posted (Actual): April 4, 2022

Study Record Updates

• Last Update Posted (Actual): January 10, 2024
• Last Update Submitted That Met QC Criteria: January 9, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Trauma, Nervous System; Spinal Cord Diseases; Spinal Cord Injuries
• Other Study ID Numbers: NVG-291-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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