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Trial registered on ANZCTR


Registration number
ACTRN12623000836639
Ethics application status
Approved
Date submitted
12/07/2023
Date registered
4/08/2023
Date last updated
9/08/2024
Date data sharing statement initially provided
4/08/2023
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 immunocompromised patients.
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 (COVID-EDV) in non-COVID-19 Infected, immunocompromised patients.
Secondary ID [1] 310115 0
None
Universal Trial Number (UTN)
Trial acronym
COVID-EDV IC/ENG 14
Linked study record
COVID-EDVs are being developed as a potential COVID-19 vaccine to protect COVID-vulnerable people such as those suffering from cancer and who have a compromised immune system. This study is a follow-up of ACTRN12621001159842 where the COVID-EDVs were initially tested in healthy volunteers.

Health condition
Health condition(s) or problem(s) studied:
COVID-19 330684 0
Condition category
Condition code
Infection 327501 327501 0 0
Other infectious diseases
Respiratory 327502 327502 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 and a glycolipid a-galactosyl ceramide in the EDV, called COVID-EDVs, in non-COVID-19 infected immunocompromised patients. Participants must be 18 years and older and will receive the COVID-EDV vaccine administered as a 0.6mL intramuscular injection at a single dose level of 9 billion COVID-EDVs at Day 1, 21 and at 4 months.

Participants will undergo a Screening Visit, 3 injections of the COVID-EDV vaccine, a 28 Day Safety Follow-up Visit and 2 month, 6 month and 9 month follow-up visits. The total treatment duration is 4 months, with a total on study duration of approximately 9 months.

All doses will be administered in a clinic with 1 hour of safety monitoring on dosing days. This includes vital signs, laboratory tests and adverse event monitoring. The study will be conducted as a multi-centre trial, enrolling up to 100 participants in total.

During the informed consent process, participants are provided a Participant Information Sheet/Consent Form that outlines what participation in the study involves as well as the purpose of the research. During this process, the Principle Investigator counsels the participant on the importance of adhering to the protocol visits.

The Study Co-ordinators are responsible for communicating with participants and ensuring they are scheduled for upcoming study visits. All communications are recorded in the source notes and the study monitors assess adherence to study visits both remotely and during on-site monitoring visits.
Intervention code [1] 326515 0
Prevention
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 335365 0
The primary objective of this trial is to assess the safety and tolerability of COVID-EDVs administered intramuscularly (IM) as three injections (Day 1, 21 and at 4 months) in non-COVID-19-infected immunocompromised patients.
Safety assessments 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

Of the 18 evaluated participants from the dose escalation stage of the ENG12 healthy volunteer trial studying COVID-EDVs, most related adverse events were identified as Grade 1, with Myalgia – Deltoid (44.4%), Injection Site Rash and Swelling (11.1%), Headache (13.9%) and Malaise/Fatigue (13.9%) considered the most common occurrences.

Participants will remain in the clinic for a minimum of 1 hour after each dose for safety monitoring, where participants vital signs will be recorded, and laboratory samples taken as per protocol schedule.

AEs associated with COVID-EDV administration intramuscularly will be assessed using the AE toxicity grading scale Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The Investigator is responsible for ensuring that all AEs that are observed by themselves and members of the clinical team or are reported by the subject that occur after signing of the informed consent through to the safety follow-up (Day 28), are recorded in the subject’s medical records and reported on the appropriate CRF pages (e.g. Adverse Event form).
The Safety Monitoring Committee will review accumulated safety data including, but not limited to, incidence of adverse events (AEs) and Serious Adverse Events (SAEs), dose limiting toxicities (DLTs), clinically significant changes in vital signs and clinical laboratory tests, to determine if there are any emerging safety issues.

Laboratory tests will be performed by the local pathology laboratory using whole blood samples for serum biochemistry, FBC/haematology and Coagulation tests as well as Urinalysis by dipstick analysis. A COVID-19 PCR test will be performed by local laboratory to confirm the absence of infection.

Vital signs include resting pulse, respiration, temperature, blood pressure. Blood pressure will be measured using the same arm throughout the study in sitting position after 5 minutes rest. Aural or oral temperature will be measured electronically. If an elevated temperature is recorded it should be measured at least hourly (if supplementary to scheduled assessments) until it returns to within normal range, or is considered by the Investigator to be stable with no associated clinical cause other than immune response, in which case the subject may be discharged at the Investigators discretion. Pulse rate will be measured under the same conditions as the blood pressure measurements either manually by palpation of the radial pulse, or electronically.
Timepoint [1] 335365 0
The primary timepoints in this trial are Baseline; Day 1; Day 21; Day 28; 2-Months; 4-Months; 6-Months: and 9-Months.

The “baseline value” is the value measured on Day 0, or at the Screening Visit and before first administration of investigational medicinal product. Day 1 is the day that the first dose of investigational medicinal product is administered for each participant. All subsequent doses and follow-up visits are relative to the date of the participant’s Day 1 visit.
Secondary outcome [1] 424118 0
Composite assessment of immune responses of participants receiving the COVID-EDV vaccine through:
Serum Biochemistry and Haematology assessed by pathology lab
C-Reactive Protein assessed by pathology lab
IgG and IgM antibody responses assessed by ELISA
Type I interferon response assessed by ELISA
Type II interferon response assessed by ELISA
Virus neutralising response assessed by surrogate virus neutralisation test
CD8+ T-cell response assessed by flow cytometry
Activation and proliferation of macrophages, dendritic cells and iNKT cells assessed by flow cytometry
Timepoint [1] 424118 0
The secondary timepoints in this trial are Baseline; Day 1; Day 21; Day 28; 2-Months; 4-Months; 6-Months: and 9-Months.

The “baseline value” is the value measured on Day 0, or at the Screening Visit and before first administration of investigational medicinal product. Day 1 is the day that the first dose of investigational medicinal product is administered for each participant. All subsequent doses and follow-up visits are relative to the date of the participant’s Day 1 visit.

Eligibility
Key inclusion criteria
Participants must have a primary or acquired immunocompromising condition and should be willing to comply with protocol scheduled study visits or procedures, to the best of the subject and Investigator’s knowledge.
Participants must have a Negative COVID-19 test (PCR or equivalent), a baseline body temperature of less than or equal to 37·5°C, an oxygen saturation of at least 92% at baseline and have general good health as established by medical history and physical examination.

Reproductive criteria are 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?
No
Key exclusion criteria
1. Medical history of SARS-CoV-2 infection within 3 months of Day 1.
2. Prior vaccination with a COVID-19 vaccine or prior participation in a COVID-19 vaccine trial or prior treatment with a SARS-CoV-2 specific monoclonal antibody or convalescent COVID-19 plasma within 3 months of Day 1.
3. Significant pericardial effusions, pleural effusions or ascites.
4. Subject is currently diagnosed with Acute Respiratory Distress Syndrome.
5. Subject has experienced a history of uncontrolled: coronary artery disease, with or without angina pectoris or myocardial infarction, symptomatic congestive heart failure (New York Heart Association greater than Class II), uncontrolled hypertension (systolic greater than 160 mmHg or diastolic greater than 100 mmHg), or cardiac arrhythmias requiring anti-arrhythmic therapy.
6. 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.
7. Current active or uncontrolled severe infection.
8. 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: major surgery.
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. 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.
11. 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.
12. Platelet disorder or other bleeding disorder that may cause contraindication to injection. 13. Prior administration of other investigational agents less than or equal to 28 days prior to study Day 1.
14. Prior administration of attenuated vaccine in last 30 days prior to first dose.
15. Prior administration of inactivated vaccine in last 14 days prior to first dose.

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)
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
4/04/2023
Date of last participant enrolment
Anticipated
4/04/2025
Actual
Date of last data collection
Anticipated
5/01/2026
Actual
Sample size
Target
100
Accrual to date
1
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 25171 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment postcode(s) [1] 40839 0
3065 - Fitzroy

Funding & Sponsors
Funding source category [1] 314276 0
Commercial sector/Industry
Name [1] 314276 0
EnGeneIC Pty Limited
Country [1] 314276 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
EnGeneIC Pty Limited
Address
2/25 Sirius Rd
Lane Cove West
NSW 2066
Country
Australia
Secondary sponsor category [1] 316216 0
None
Name [1] 316216 0
Address [1] 316216 0
Country [1] 316216 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 313395 0
St Vincent's Hospital Melbourne Human Research Ethics Committee
Ethics committee address [1] 313395 0
Research Governance Unit
Level 1
93-103 Victoria Parade
Fitzroy VIC 3065
Ethics committee country [1] 313395 0
Australia
Date submitted for ethics approval [1] 313395 0
02/09/2022
Approval date [1] 313395 0
25/10/2022
Ethics approval number [1] 313395 0
HREC 176/22

Summary
Brief summary
A Phase I/IIa, first-in-human study of EDV nanocells packaged with SARS-CoV-2 spike protein and alpha galacosylceramide adjuvant (COVID-EDV) as a COVID-19 vaccine in immunocompromised patients. COVID-EDVs are being developed as a potential anti-COVID-19 vaccine to protect COVID-vulnerable people such as those suffering from cancer and who have a compromised immune system. This trial is a follow-up of the previous healthy volunteer trial ACTRN12621001159842.

The primary objective of this trial is to assess the safety and tolerability of COVID-EDVs administered intramuscularly (IM) in non-COVID-19-infected immunocompromised patients. The study follows an open label, non-randomised study design using a COVID-EDV dose level that was determined previously in a healthy volunteer trial. The study is designed to assess the ability of COVID-EDV to stimulate and support the body’s immune response to produce antibodies that can fight COVID-19.

The COVID-EDV vaccine will be administered as three injections on Day 1, 21 and at 4 months. Each participant must have a immunocompromised condition and will be involved in the study for 9 months. A total of 100 participants will be recruited to the study.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 127998 0
Prof Kumar Visvanathan
Address 127998 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 127998 0
Australia
Phone 127998 0
+61 03 9288 2745
Fax 127998 0
Email 127998 0
[email protected]
Contact person for public queries
Name 127999 0
Scott Pattison
Address 127999 0
EnGeneIC Pty Limited
Level 4 Building 53
11 Julius Ave
North Ryde NSW 2113
Country 127999 0
Australia
Phone 127999 0
+61 02 9420 5844
Fax 127999 0
Email 127999 0
[email protected]
Contact person for scientific queries
Name 128000 0
Jennifer MacDiarmid
Address 128000 0
EnGeneIC Pty Limited
Level 4 Building 53
11 Julius Ave
North Ryde NSW 2113
Country 128000 0
Australia
Phone 128000 0
+61 02 9420 5844
Fax 128000 0
Email 128000 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
Undecided


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.