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Trial registered on ANZCTR


Registration number
ACTRN12621001159842
Ethics application status
Approved
Date submitted
18/08/2021
Date registered
27/08/2021
Date last updated
14/10/2022
Date data sharing statement initially provided
27/08/2021
Type of registration
Retrospectively registered

Titles & IDs
Public title
A study of the safety of EDV nanocells packaged with spike-protein plasmid and glycolipid as a COVID-19 vaccine in healthy volunteers.
Scientific title
A Phase I/IIa Trial to determine safety of EDV nanocells packaged with a plasmid encoding SARS-CoV-2 spike protein in the EDV and a glycolipid a-galactosyl ceramide (EDV-plasmid-spike-GC) in non-COVID-19 infected volunteers.
Secondary ID [1] 305041 0
None
Universal Trial Number (UTN)
Trial acronym
COVID-EDV/ENG12
Linked study record

Health condition
Health condition(s) or problem(s) studied:
COVID-19 323220 0
Condition category
Condition code
Infection 320804 320804 0 0
Other infectious diseases
Respiratory 320887 320887 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a Phase I/IIa, open label study to determine the safety of EDV nanocells packaged with a plasmid encoding SARS-CoV-2 spike protein in the EDV and a glycolipid a-galactosyl ceramide (EDV-plasmid-spike-GC) in non-COVID-19 infected volunteers, 18 years and older.

Participants who are enrolled into Cohort 1 will receive 0.6mL intramuscular dose of 8 x 10^9 EDV-plasmid-spike-GC. Once the safety and tolerability of this dose level has been confirmed (and approximately within 1 week of Cohort 1 completion), new participants will be assigned to Cohort 2, receiving 0.6mL intramuscular dose of 9 x 10^9 EDV-plasmid-spike-GC. Once the safety and tolerability of this dose level has been confirmed (and approximately within 1 week of Cohort 2 completion), new participants will be assigned to Cohort 3, receiving 0.6mL intramuscular dose of 1 x 10^10 EDV-plasmid-spike-GC. Cohorts 1-3 will still enroll 6 participants each.

The dose level of 9 x 10^9 EDV-plasmid-spike-GC has been determined by the Safety Committee to be the most safe and efficacious. All new participants will now be administered this dose level, up to 200 participants total.

All doses will be administered in clinic with 3 hour safety monitoring on dosing days. This includes vital signs, laboratory tests and adverse event monitoring.
Intervention code [1] 321435 0
Prevention
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 328613 0
Assess the safety and tolerability of EDV-plasmid-spike-GC administered intramuscularly as two doses in non-COVID-19 infected volunteers. Safety assessment will involve standard clinical monitoring of the following in hospital medical records:
- Dose Limiting Toxicities and Adverse Events
- Clinical Laboratory Tests (Full Blood Count, Chemistry, C-Reactive Protein, Coagulation Studies, Creatinine Clearance, Urinalysis, Cytokines)
- Vital Signs
- Physical Examination
- 12-Lead Electrocardiogram
Timepoint [1] 328613 0
Baseline; Day 1; Day 21; Day 28; 2-Months; 3-Months; and 6-Months.
Primary outcome [2] 328614 0
Composite assessment of immune responses of participants receiving the EDV-plasmid-spike-GC through:
Serum Biochemistry and Haematology
C-Reactive Protein
IgG and IgM antibody responses
Type I interferon response
Type II interferon response
Virus neutralising response
CD8+ T-cell response
Activation and proliferation of macrophages, dendritic cells and iNKT cells
Timepoint [2] 328614 0
Baseline; Day 1; Day 21; Day 28; 2-Months; 3-Months; and 6-Months.
Secondary outcome [1] 399637 0
N/A
Timepoint [1] 399637 0
N/A

Eligibility
Key inclusion criteria
1. Volunteers (male or female) non-COVID-19 infected.
2. Aged greater than or equal to 18 years.
3. No medical history of SARS-CoV-2 infection within 4 months of Day 1.
4. The subject (or subject’s legally authorised representative) has provided voluntary signed informed consent.
5. Subject should be willing to comply with protocol scheduled study visits or procedures, to the best of the subject and Investigator’s knowledge.
6. Have a baseline body temperature of less than or equal to 37·5°C and have general good health as established by medical history and physical examination.
7. Reproductive criteria as follows:
• Female subjects who are of non-reproductive potential (i.e., post menopausal by history - no menses for greater than or equal to 1 year and follicle-stimulating hormone (FSH) level consistent with post-menopausal status; OR history of hysterectomy; OR history of bilateral tubal ligation; OR history of bilateral oophorectomy).
• Female subjects of childbearing potential must have a negative serum pregnancy test within 14 days of the first dose.
• Female subjects must be willing to use highly effective methods of birth control during the period of therapy and for 6 months following the last study drug administration. Highly effective methods of birth control include sexual abstinence, hormonal birth control, or intrauterine device (women), vasectomy or a condom with spermicide (men) in combination with barrier methods.
• Male subjects must be willing to use highly effective methods of birth control during the period of therapy and for 6 months following the last study drug administration.
• All study subjects must be willing to ensure that corresponding sexual partners practice these same methods of highly effective birth control for the same duration.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Prior intervention for SARS-CoV-2 prophylaxis within 4 months of Day 1.
2. Prior treatment with a SARS-CoV-2 specific monoclonal antibody or convalescent COVID-19 plasma within 4 months of Day 1.
3. Significant pericardial effusions, pleural effusions or ascites.
4. Subject has experienced a history of coronary artery disease, with or without angina pectoris or myocardial infarction, symptomatic congestive heart failure (New York Heart Association > Class II), uncontrolled hypertension (systolic > 160 mmHg or diastolic > 100 mmHg), or cardiac arrhythmias requiring anti-arrhythmic therapy.
5. History of uncontrolled arterial or venous thrombosis. Subjects with a history of arterial or venous thrombosis are eligible if the subject is controlled via ongoing therapeutic intervention.
6. Active or uncontrolled severe infection.
7. Received the following procedures within 28 days prior to receiving their first dose (Day 1), (or has not recovered from the toxic effects of such therapy) including:
• radiotherapy
• major surgery.
8. History of myocarditis.
9. QTc interval prolonging medicines should be reviewed and where possible their use should be minimized and alternate medicines that are not QTc interval prolonging considered as substitutes.
10. Known allergy/hypersensitivity to investigational components or excipients (monoclonal antibody infusions, interferon therapy or bacterial vaccines).
11. Any kind of disorder that, in the opinion of the Investigator, may compromise the ability of the subject to give written informed consent and/or to comply with all required study procedures.
12. History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the Investigator would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.
13. Platelet disorder or other bleeding disorder that may cause contraindication to injection.
14. Prior administration of other investigational agents less than or equal to 15 days prior to study Day 1.
15. Prior administration of attenuated vaccine in last 30 days.
16. Prior administration of inactivated vaccine in last 14 days.

Study design
Purpose of the study
Prevention
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is not concealed.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1 / Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
26/08/2021
Date of last participant enrolment
Anticipated
31/10/2022
Actual
Date of last data collection
Anticipated
28/04/2023
Actual
Sample size
Target
200
Accrual to date
78
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 20242 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment hospital [2] 21354 0
Sydney Adventist Hospital - Wahroonga
Recruitment postcode(s) [1] 34975 0
3065 - Fitzroy
Recruitment postcode(s) [2] 36246 0
2076 - Wahroonga

Funding & Sponsors
Funding source category [1] 309412 0
Commercial sector/Industry
Name [1] 309412 0
EnGeneIC Pty Limited
Country [1] 309412 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
EnGeneIC Pty Limited
Address
Building 2/25 Sirius Rd.
Lane Cove West
NSW 2066
Country
Australia
Secondary sponsor category [1] 310403 0
None
Name [1] 310403 0
Address [1] 310403 0
Country [1] 310403 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309216 0
St Vincent's Hospital Melbourne Human Research Ethics Committee
Ethics committee address [1] 309216 0
Research Governance Unit
Level 1
93-103 Victoria Parade
Fitzroy VIC 3065
Ethics committee country [1] 309216 0
Australia
Date submitted for ethics approval [1] 309216 0
16/06/2021
Approval date [1] 309216 0
28/06/2021
Ethics approval number [1] 309216 0
HREC 315/20

Summary
Brief summary
This is the initial Phase I/IIa, first-in-human study of EDV nanocells packaged with SARS-CoV-2 spike protein and alpha galacosylceramide adjuvant (EDV-plasmid-spike-GC) as a COVID-19 vaccine.

The study follows an open label, non-randomised dose escalation study design across three dose levels, whereby the EDV-plasmid-spike-GC is administered intramuscularly (IM) at a dosage dependent on the cohort in order to assess the safety and tolerability of the vaccine in healthy volunteers 18 years and older.

Up to a total of 200 participants will be recruited to the study, at 6 per cohort during dose escalation. Each cohort follows the same timepoints of dosing on Days 1 and 21, followed by subsequent visits at 28 days, 2 months, 3 months and 6 months. Adverse events and DLT evaluation will occur between Day 1 and 28 in order to assess the safety and tolerability of each dose level before continuing to the next cohort. Once a recommended dose level has been identified from one of the cohorts, recruitment will continue until a maximum of 200 participants.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 113378 0
Prof Kumar Visvanathan
Address 113378 0
Eastern Hill Campus
The University of Melbourne
4th Floor, Clinical Sciences Building,
St. Vincent's Hospital Melbourne
41 Victoria Parade, Fitzroy Victoria 3065 Australia
Country 113378 0
Australia
Phone 113378 0
+61 03 9288 2745
Fax 113378 0
Email 113378 0
[email protected]
Contact person for public queries
Name 113379 0
Joshua Barnes
Address 113379 0
EnGeneIC Pty Limited Building 2/25 Sirius Rd. Lane Cove West, NSW 2066
Country 113379 0
Australia
Phone 113379 0
+61 02 94205844
Fax 113379 0
Email 113379 0
[email protected]
Contact person for scientific queries
Name 113380 0
Jennifer MacDiarmid
Address 113380 0
EnGeneIC Pty Limited
Building 2/25 Sirius Rd.
Lane Cove West,
NSW 2066
Country 113380 0
Australia
Phone 113380 0
+61 03 9420 5833
Fax 113380 0
Email 113380 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


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
SourceTitleYear of PublicationDOI
EmbaseNanocell COVID-19 vaccine triggers a novel immune response pathway producing high-affinity antibodies which neutralize all variants of concern.2023https://dx.doi.org/10.3389/fimmu.2022.1038562
N.B. These documents automatically identified may not have been verified by the study sponsor.