Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621000303842
Ethics application status
Approved
Date submitted
22/01/2021
Date registered
18/03/2021
Date last updated
11/01/2023
Date data sharing statement initially provided
18/03/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase I Safety Study of NVG-291 in Healthy Adults
Scientific title
A Randomized, Triple-Blind, Placebo-Controlled Phase I Study of Single and Multiple Ascending Doses of NVG-291 in Healthy Subjects
Secondary ID [1] 303237 0
NVG-291-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Spinal cord injury 320392 0
Condition category
Condition code
Neurological 318299 318299 0 0
Other neurological disorders
Injuries and Accidents 318300 318300 0 0
Other injuries and accidents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
NVG-291 is a drug injected under the skin (subcutaneous). 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 received 1 dose on 1 day only. Doses began with 0.032 mg/kg (Cohort 1) and increased until 0.864 mg/kg (Cohort 6). Each cohort began after a safety review committee reviewed the data from the previous cohort. An additional cohort was enrolled at the end of Part 1, to be dosed at 0.864 mg/kg, to assess CSF drug levels.
In Part 2 (MAD), postmenopausal female participants received 1 dose daily for for 14 consecutive days. The starting dose for Part 2 was 0.384 mg/kg (2 dose levels lower than the maximum dose achieved during Part 1). There were 3 cohorts in Part 2. The maximum daily dose in Part 2 did not exceed the maximum daily dose tolerated in Part 1.
In Part 3 (MAD), male and pre-menopausal female participants will received 0.547 mg/kg daily for for 14 consecutive days.
All study parts will be monitored by a qualified CRA to assure study procedures and dose administrations are performed as per protocol.
Intervention code [1] 319540 0
Treatment: Drugs
Comparator / control treatment
Salt water is being used as a placebo and will be injected under the skin (subcutaneous). In Part 1 (SAD), participants receive 1 dose on 1 day only and in Parts 2 and 3 (MAD), participants receive 1 dose every day for 14 days. Doses will start low and increase for every cohort in Parts 1 and 2. All participants in Part 3 will receive the same daily dose.
Control group
Placebo

Outcomes
Primary outcome [1] 326274 0
Safety and tolerability as assessed by vital signs, clinical laboratory tests (hematology, biochemistry, hormones, and urinalysis), immunogenicity tests, and incidence of adverse events.
Timepoint [1] 326274 0
Assessed daily in the clinic and 7 days following the last dose for all SAD and MAD cohorts
Primary outcome [2] 326275 0
The primary safety analyses will be conducted on the incidence of subjects with AEs (including SAEs and discontinuations due to AEs), changes in PE or vital signs, and incidence of subjects with abnormal clinical laboratory values.
Timepoint [2] 326275 0
Determined on completion of all dosing and safety reviews
Secondary outcome [1] 390864 0
The primary PK analyses (plasma) will include (where sufficient data are available) AUC0-t, AUC0-inf, Cmax, %AUC extrapolated, t1/2lambdaz, Cl/F, Vz/F, and Tmax.
Timepoint [1] 390864 0
Assessed on Day 1 (SAD and MAD) and Day 14 (MAD only)
Secondary outcome [2] 390866 0
Immunogenicity (serum) analyses will be conducted to determine the presence of anti-drug antibodies in response to dosing with NVG-291.
Timepoint [2] 390866 0
Assessed on Day 1 (SAD and MAD), Day 8 (SAD and MAD) and Day 21 (MAD only)

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
6/05/2021
Actual
6/05/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
74
Accrual to date
58
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 18479 0
CMAX Clinical Research Pty Ltd - Adelaide
Recruitment hospital [2] 21073 0
Nucleus Network - Melbourne
Recruitment postcode(s) [1] 32797 0
5000 - Adelaide
Recruitment postcode(s) [2] 35926 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 307647 0
Commercial sector/Industry
Name [1] 307647 0
NervGen Pharma Corp.
Country [1] 307647 0
Canada
Primary sponsor type
Commercial sector/Industry
Name
NervGen Pharma Corp.
Address
595 Burrard Street, Suite 1703
Vancouver, BC V7X 1J1
Country
Canada
Secondary sponsor category [1] 308339 0
None
Name [1] 308339 0
Address [1] 308339 0
Country [1] 308339 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307686 0
Bellberry Human Research Ethics Committee
Ethics committee address [1] 307686 0
123 Glen Osmond Road
Eastwood Adelaide, SA 5063
Ethics committee country [1] 307686 0
Australia
Date submitted for ethics approval [1] 307686 0
20/01/2021
Approval date [1] 307686 0
13/04/2021
Ethics approval number [1] 307686 0

Summary
Brief summary
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 participants. The trial is split into three parts, starting with Part 1 (SAD) and then Parts 2 and 3 (MAD). In Part 1 (SAD), participants receive 1 dose on 1 day only and in Parts 2 and 3 (MAD), participants receive 1 dose every day for 14 days.
Trial website
Trial related presentations / publications
Public notes
Participants who receive of a COVID-19 vaccination within 3 weeks prior to Day -1 will be excluded from the study

Contacts
Principal investigator
Name 108138 0
Prof Philip Ryan
Address 108138 0
Nucleus Network
5th floor, Burnet Tower, AMREP Precinct
89 Commercial Rd,
Melbourne, VIC 3004
Country 108138 0
Australia
Phone 108138 0
+61 0438 009 787
Fax 108138 0
Email 108138 0
[email protected]
Contact person for public queries
Name 108139 0
Mr Andrew Walker
Address 108139 0
Nucleus Network
5th floor, Burnet Tower, AMREP Precinct
89 Commercial Rd,
Melbourne, VIC 3004
Country 108139 0
Australia
Phone 108139 0
+61 0404 225 972
Fax 108139 0
Email 108139 0
[email protected]
Contact person for scientific queries
Name 108140 0
Prof Philip Ryan
Address 108140 0
Nucleus Network
5th floor, Burnet Tower, AMREP Precinct
89 Commercial Rd,
Melbourne, VIC 3004
Country 108140 0
Australia
Phone 108140 0
+61 0438 009 787
Fax 108140 0
Email 108140 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
To be used for regulatory purposes only.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.