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Trial registered on ANZCTR


Registration number
ACTRN12620000817943
Ethics application status
Approved
Date submitted
3/08/2020
Date registered
14/08/2020
Date last updated
8/09/2020
Date data sharing statement initially provided
14/08/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase 1/2 randomized, placebo-controlled, multi-centre study to evaluate the safety and immunogenicity of COVID-19 Vaccine in Healthy Adults
Scientific title
A randomized, observer-blind, placebo-controlled, Phase I/II study to evaluate the safety, reactogenicity and immunogenicity of Receptor Binding Domain (RBD) SARS-CoV-2 (COVID-19) Hepatitis B surface antigen (HBsAg) virus like particle (VLP) Vaccine in Healthy Adults
Secondary ID [1] 301714 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
SARS-CoV-2 318459 0
COVID-19 318475 0
Condition category
Condition code
Infection 316465 316465 0 0
Other infectious diseases
Respiratory 316607 316607 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
RBD SARS-CoV-2 HBsAg VLP Vaccine, administered at two dose amounts, 5mcg and 25 mcg, by intramuscular injection by Investigators (or delegate) during in-clinic visit. Phase 1 will include three cohorts, to receive either 5mcg dose on Day 0 and 28; 25mcg dose on Days 0 and 28 or placebo on Day 0 and 28.

Phase 2 will evaluate both dose amounts either as single dose (given at day 0, with placebo at Day 28) or two doses (at Days 0 and 28). Participants will be randomised into one of 5 cohorts. These are 1) 5mcg dose administered on Days 0 and 28; 2) 25mcg dose administered on Days 0 and 28; 3) 5mcg dose administered on Days 0 and placebo on Day 28; 4) 25mcg dose administered on Days 0 and placebo on Day 28, or 5) placebo on day 0 and 28.

Phase 2 will commence following DSMB review of safety data from Phase 1.

Two groups of participants will be enrolled. Phase 1 will include a group of healthy adults aged 18-45. Phase 2 will include a separate group of healthy adults aged 18 - 79 years.

Participants will return to site at day 7 and 14 from vaccine administration dates to undergo safety assessments and blood sampling for immunogenicity evaluation. Further on site assessments are conducted monthly or bi-monthly for up to 180 days from date of first vaccine administration.
Intervention code [1] 318220 0
Treatment: Drugs
Comparator / control treatment
Phase I and II: Placebo vaccine containing aluminium hydroxide suspension, administered as two doses (0.25mL per dose) on days 0 and 28
Control group
Placebo

Outcomes
Primary outcome [1] 324616 0
Phase I: To assess the composite endpoints of vaccine safety and reactogenicity of a two-dose schedule of two dose amounts of RBD SARS-CoV-2 HBsAg VLP vaccine as compared with two-dose administration of placebo in healthy adults aged 18 - 45 years as determined through participant reported (solicited and unsolicited) and clinically identified local and systemic adverse events (e.g. blood tests, vital signs, physical examination).
Timepoint [1] 324616 0
Participant reported events reported daily for 7 days post-vaccination and then on occurrence up to 180 days post-vaccination
Primary outcome [2] 324617 0
Phase II; To assess the immune response of a two-dose schedule of two dose amounts of RBD SARS-CoV-2 HBsAg VLP vaccine as compared with two-dose administration of placebo in healthy adults aged 18 - 79 years as determined through changes in participant immunity 56 days from first dose.

To assess the immune response following a single-dose schedule of RBD SARS-CoV-2 HBsAg VLP vaccine as compared with placebo in healthy adults aged 18 - 79 years as determined through changes in participant immune response 56 days after receiving the vaccine dose. Immune response will be measured through analysis of blood samples.
Timepoint [2] 324617 0
Increase in neutralising antibody titres as measured through to day 56
Primary outcome [3] 324618 0
Phase II; To assess the composite endpoints of safety and reactogenicity of a the single and two-dose schedule of RBD SARS-CoV-2 HBsAg VLP vaccine administration as compared with placebo in healthy adults aged 18 - 79 years as determined through participant reported and clinically identified local and systemic adverse events. This will include safety blood assessment and the recording of solicited and unsolicited local and systemic adverse events by participants via an electronic diary or by the clinical staff as part of scheduled clinic visits
Timepoint [3] 324618 0
Participant reported events reported daily for 7 days post-vaccination and then on occurrence up to 180 days post-vaccination
Secondary outcome [1] 385222 0
Phase I; To assess the immune response of a two-dose schedule of RBD SARS-CoV-2 HBsAg VLP vaccine as compared with two-dose administration of placebo in healthy adults aged 18 - 45 years as determined through changes in participant serum blood immune response 28 days after receiving the second vaccine dose and through assessment of cellular immune response as taken from PBMC samples.
Timepoint [1] 385222 0
Increase in neutralising antibody titres as measured at Day 14, 28, and 56 from date of first vaccine administration.

Eligibility
Key inclusion criteria
1. Male or Female aged 18 to 79 years (both inclusive)
a. Phase I: Subjects aged 18 to 45 years (both inclusive)
b. Phase II: Subjects aged 18 to 79 years (both inclusive)
2. Healthy participants as determined by medical history, physical examination, vital signs and clinical laboratory examination with no clinically significant deviations as judged by the Investigator at screening and randomization (Day 0)
3. Test negative for SARS-CoV-2 infection by RT-PCR test at screening
4. Test negative for SARS-CoV-2 IgG antibody by at screening
5. Capable and willing to provide written informed consent prior to the performance of any study-specific procedures
Minimum age
18 Years
Maximum age
79 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Receipt of medications or vaccines intended to prevent or treat COVID-19 infection in the past
2. Fever (non-axillary temperature > 37.5 ºC) or any other symptoms of infection that have not completely resolved including respiratory symptoms/illnesses within the past 3 days from randomization (Day 0)
3. Participants with a BMI > 35 kg/m2.
4. Presence of current active viral or bacterial infection, at screening and randomization (Day 0), which is determined by the Investigator to be of clinical significance
5. Individuals with history of any major pulmonary, cardiovascular, renal, neurological, metabolic, gastrointestinal, hepato-biliary, blood dyscrasia, uncontrolled hypertension and diabetes, clinically significant chronic pulmonary disease, asthma (with the exception of history of resolved childhood asthma), immunological and autoimmune diseases or any condition which in the opinion of the Investigator might interfere with the evaluation of the study objectives
6. Individuals currently working in occupations with high risk of exposure to SARS-CoV-2 (e.g. healthcare worker in direct care of COVID-19 patients, front line workers in COVID-19 hotspots/outbreak areas)
7. Pregnant or lactating women or willingness/intention to become pregnant during the study
8. Men and Women (of child-bearing potential) not agreeing to use adequate contraception during the study
9. Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the Investigator, contraindicate intramuscular injection
10. Severely immunocompromised subjects. This exclusion category comprises a) subjects with solid organ transplantation; b) subjects with bone marrow transplantation; c) subjects under chemotherapy/radiotherapy; d) subjects with primary immunodeficiency; e) treatment with any anticytokine therapies. f) treatment with oral or intravenous steroids defined as daily doses of 10mg prednisolone or equivalent for longer than 3 months from the time of screening, or probable use of oral or intravenous steroids in the following four weeks
11. History of solid or non-solid malignancy or lymphoma (except basal cell carcinoma of the skin and cervical carcinoma in situ)
12. Known allergy to any component of the RBD SARS-CoV-2 HBsAg VLP Vaccine, or serious adverse reactions to the vaccine, such as urticaria, dyspnea, and angioedema.
13. A history of anaphylaxis to a vaccine, food, drug, toxin or other exposure.
14. Known hypersensitivity reactions to yeast.
15. Positive test result at screening for human immunodeficiency virus (Types 1 or 2) antibody, hepatitis B surface antigen, or hepatitis C virus antibody.
16. Clinical laboratory tests of blood and urine not within the normal range and show clinically relevant deviations as judged by the Investigator
17. History of demyelinating disease or Guillain Barre syndrome
18. Eczema or other significant skin lesion or infection at the site of vaccination
19. Planned or actual receipt of any vaccine other than the study intervention within 30 days before and after each study vaccination
20. Positive screen for drugs of abuse#or alcohol (breath test) at screening and randomization (Day 0).
21. Participants who currently smoke 10 cigarettes or equivalent per day
22. Subjects not willing to/unable to comply with study procedures
23. Participating in any other study and have received any other investigational medication or device within 30 days prior to randomization or are taking part in a non-medication study which, in the opinion of the Investigator, would interfere with the interpretation of the assessments in this study.
24. Receipt of blood/blood products/immunoglobulins or donation of blood/ blood products 8 weeks prior to vaccination or planned receipt or donation during the study period
25. Any other medical condition which in the opinion of the Investigator may affect the subject’s safety or study participation and conduct

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)
Central randomisation
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation table created by computer software
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
Intervention assignment
Other design features
Phase
Phase 1 / Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 17185 0
Nucleus Network - Melbourne
Recruitment postcode(s) [1] 30888 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 306152 0
Commercial sector/Industry
Name [1] 306152 0
Serum Institute of India Pvt Ltd
Address [1] 306152 0
212/2, Off Soli Poonawalla Road, Hadapsar
Pune - 411028
Country [1] 306152 0
India
Primary sponsor type
Commercial sector/Industry
Name
Accelagen Pty Ltd
Address
Suite 1.02, 722 High Street
Kew East VIC 3102
Country
Australia
Secondary sponsor category [1] 306621 0
Commercial sector/Industry
Name [1] 306621 0
Serum Institute of India Pvt Ltd
Address [1] 306621 0
212/2, Off Soli Poonawalla Road, Hadapsar
Pune - 411028
Country [1] 306621 0
India

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 306369 0
Alfred Health
Ethics committee address [1] 306369 0
55 Commercial Rd, Melbourne VIC 3004
Ethics committee country [1] 306369 0
Australia
Date submitted for ethics approval [1] 306369 0
03/07/2020
Approval date [1] 306369 0
19/08/2020
Ethics approval number [1] 306369 0

Summary
Brief summary
The receptor-binding domain (RBD) in SARS-CoV-2 S protein has been identified as the component required for coronaviruses to enter the human cells using the human receptor angiotensin converting enzyme 2 (ACE2).

The investigational vaccine, RBD SARS-CoV-2 HBsAg VLP vaccine, is a subunit vaccine where the RBD antigen is conjugated to the hepatitis B surface antigen to allow the stimulation of the immune system to produce anti-RBD (CoV2 Receptor binding domain) antibodies.

The study will be conducted in two stages: phase I and phase II. Phase I will include healthy adults aged 18 - 45 years and evaluate the safety and immunogenicity reported after two-doses of vaccine when compared with placebo. Phase II will include a separate group of healthy adults participants aged 18 - 79 years and evaluate the safety and immunogenicity reported after receiving a single dose or two-doses of vaccine 28 days apart when compared with placebo.

Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 103638 0
A/Prof Paul Griffin
Address 103638 0
Nucleus Network
89 Commercial Road
Melbourne, Victoria, 3004
Australia
Country 103638 0
Australia
Phone 103638 0
+61385939801
Fax 103638 0
Email 103638 0
p.griffin@nucleusnetwork.com.au
Contact person for public queries
Name 103639 0
Mr Greg Plunkett
Address 103639 0
Accelagen Pty Ltd
Suite 1.02, 722 High Street
Kew East VIC 3102
Country 103639 0
Australia
Phone 103639 0
+61410552020
Fax 103639 0
Email 103639 0
RBDCovid@Accelagen.com.au
Contact person for scientific queries
Name 103640 0
Mr Greg Plunkett
Address 103640 0
Accelagen Pty Ltd
Suite 1.02, 722 High Street
Kew East VIC 3102
Country 103640 0
Australia
Phone 103640 0
+61410552020
Fax 103640 0
Email 103640 0
RBDCovid@Accelagen.com.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Data from overall study population will be available within the clinical study report provided to participating sites, and scientific publications as prepared by Sponsor representatives or Study Investigators.
What supporting documents are/will be available?
No other documents available
Summary results
No Results