A Phase 3b/4 Randomised Trial of 3 Doses of Protein-based Covid-19 Vaccine (SpikoGen)

Study Overview
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Brief Summary
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This study will determine the immunogenicity of Spikogen in vaccine naïve individuals. Spikogen will be administered as two doses 1 month apart with a third booster dose either 1 or 3 months after the second dose. This study will provide key data on SARS-CoV-2 antibody responses.

Detailed Description
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The SARS-CoV-2 outbreak has caused millions of deaths globally. It has a particularly high mortality rate in elderly people and those with chronic disease where mortality rates can be as high as 20-30%. SARS-COV-2 vaccines remain a key priority to help fight the current pandemic. COVID-19 vaccines prevent symptomatic infection and may help reduce virus transmission. Spikogen® vaccine, also known as Covax-19™ in Australia, is an adjuvanted recombinant protein Covid-19 vaccine has recently been approved by the Iranian FDA for emergency use in Iran in adults as a primary vaccine course and booster dose, after meeting its primary efficacy endpoint in a Phase 3 trial in 16,876 participants randomised 3:1 to receive Spikogen vaccine or saline placebo via two intramuscular doses 3 weeks apart where Spikogen vaccine demonstrated significant protection against serious infection with the delta variant. Approximately 5-10% of the broader Australian population and an even higher proportion of the indigenous populations remains unvaccinated despite current availability of these vaccines. One reason is that some people have medical contraindications to the current vaccines, such as serious allergies to the vaccine components such as polyethyleneglycol (PEG) in the mRNA vaccines. Spikogen vaccine is made using a recombinant protein approach with the SARS-CoV-2 spike protein synthesized in an insect cell line grown in broth. Insect cell expression of recombinant protein is a well-established vaccine manufacturing approach. Spikogen vaccine also contains a unique Australian developed adjuvant called Advax-CpG55.2, which is added to the spike protein to make the vaccine more effective. AdvaxCpG55.2 has two components, one a natural plant sugar called inulin, and the second a short synthetic oligonucleotide polymer, known as CpG55.2 oligonucleotide. Spikogen vaccine is designed to protect against SARS-CoV-2 infection. It has been shown to be effective against infection in hamster, ferret and monkey SARS-CoV-2 infection models. This study will determine the immunogenicity of Spikogen in vaccine-naïve individuals. Spikogen will be administered as two doses 31 month apart with a third booster dose given either 1 or 3 months after the second dose.

Official Title
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A Phase 3b/4 Randomised Trial of 3 Doses of Protein-based Covid-19 Vaccine (SpikoGen)

Conditions
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COVID-19

Intervention / Treatment
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* Biological: Advax-CpG55.2 adjuvanted recombinant spike protein


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to provide written informed consent Males or females* 18 years of age or older Understand and are likely to comply with planned study procedures and be available for all study visits. Have not previously had a Covid-19 vaccine and do not intend to have a non-study Covid-19 vaccine within the next 6 months Exclusion Criteria: History of Covid-19 vaccination. History of serious vaccine allergy. Pregnancy1 Have received an experimental agent within 30 days prior to the study vaccination or expect to receive another experimental agent during the trial reporting period. Any medical, social or mental condition which, in the opinion of the investigator, would be detrimental to the subjects or the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Subjects will be stratified for analysis by age, sex and seropositivity at time of study entry
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Spikogen vaccine - accelerated arm<br>Spikogen vaccine 25 micrograms by intramuscular injection on study months 0, 1 and 2 | Biological: Advax-CpG55.2 adjuvanted recombinant spike protein<br>* recombinant SARS-CoV-2 spike protein formulated with Advax-CpG55.2 adjuvant<br>* Other names: Spikogen vaccine;|
| Experimental: Spikogen vaccine - standard arm<br>Spikogen vaccine 25 micrograms by intramuscular injection on study months 0, 1 and 4 | Biological: Advax-CpG55.2 adjuvanted recombinant spike protein<br>* recombinant SARS-CoV-2 spike protein formulated with Advax-CpG55.2 adjuvant<br>* Other names: Spikogen vaccine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| First dose Seroconversion | Proportion of subjects in each group stratified by baseline antibody positivity seroconverting to spike protein antibody positivity | 2-4 weeks post first immunisation | 
| Second dose Seroconversion | Proportion of subjects in each group stratified by baseline antibody positivity seroconverting to spike protein antibody positivity | 2-4 weeks post second immunisation | 
| Third Dose Seroconversion | Proportion of subjects in each group stratified by baseline antibody positivity seroconverting to spike protein antibody positivity | 2-4 weeks post third immunisation | 
| Final Seroconversion | Proportion of subjects in each group stratified by baseline antibody positivity seroconverting to spike protein antibody positivity | through study completion, an average of 7 months | 
| First Dose GMT | Spike protein antibody Geometric Mean Titers (GMT) in each group stratified by baseline antibody positivity | 2-4 weeks post first immunisation | 
| Second Dose GMT | Spike protein antibody Geometric Mean Titers (GMT) in each group stratified by baseline antibody positivity | 2-4 weeks post second immunisation | 
| Third Dose GMT | Spike protein antibody Geometric Mean Titers (GMT)in each group stratified by baseline antibody positivity | 2-4 weeks post third immunisation | 
| Final GMT | Spike protein antibody Geometric Mean Titers (GMT)in each group stratified by baseline antibody positivity | through study completion, an average of 7 months | 
| First Dose Adverse events (AE) | AE occurring within 7 days of immunisation in each group stratified by baseline antibody positivity | 7 days post first immunisation | 
| Second Dose Adverse events (AE) | AE occurring within 7 days of immunisation in each group stratified by baseline antibody positivity | 7 days post second immunisation | 
| Third Dose Adverse events (AE) | AE occurring within 7 days of immunisation in each group stratified by baseline antibody positivity | 7 days post third immunisation | 
| Serious adverse events (SAE) | Number of Serious adverse events (SAE) occurring within study period in each group stratified by baseline antibody positivity | through study completion, an average of 7 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| First dose Vaccine efficacy | Proportion of Covid-19 infections in trial participants in each group stratified by baseline antibody positivity | From 2 weeks post-first dose to 2 weeks after second dose | 
| Second dose Vaccine efficacy | Proportion of Covid-19 infections in trial participants in each group stratified by baseline antibody positivity | From 2 weeks post-second dose to 2 weeks after third dose | 
| Third dose Vaccine efficacy | Proportion of Covid-19 infections in trial participants in each group stratified by baseline antibody positivity | From 2 weeks post-third dose through study completion, an average of 7 months | 
| Total Covid-19 infections | Proportion of breakthrough Covid-19 infections in trial participants in each group stratified by baseline antibody positivity | From first vaccine dose through study completion, an average of 7 months | 
| Seroconversion against variants of concern | Serum spike protein antibody seroconversion rates against each SARS-CoV-2 variant of concern in trial participants in each group stratified by baseline antibody positivity | 2-4 weeks post first, second and third immunisation and at study completion | 
| GMT against variants of concern | Geometric mean serum spike protein antibodies against SARS-CoV-2 variants in trial participants in each group stratified by baseline antibody positivity | 2-4 weeks post first, second and third immunisation and at study completion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sars-cov-2, coronavirus, vaccine, adjuvant, Advax, Spikogen, Covax-19