Clinical trial NCT06355232: Covid-19 and Influenza Oral Vaccine Study
Official title: A Binded, Randomised, Controlled Cross-over Trial to Assess the Safety and Efficacy of Mucosal Covid-19 and Influenza Vaccines
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: covid19 Infection
Influenza, Human
Keywords: covid-19
influenza
pandemic
mucosal
spikogen
advax
adjuvant
vaccine
Lead sponsor: Vaxine Pty Ltd
Sponsor class: INDUSTRY
Collaborators: name: Australian Respiratory and Sleep Medicine Institute Ltd
First posted: 2024-04-09
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Randomised, controlled cross-over study
Primary purpose: PREVENTION

Brief summary: The purpose of the current study is to assess the effectiveness of protein-based COVID-19 or influenza vaccines when given individually or together via oral/ sublingual mucosal route instead of intramuscular delivery. The comparator will be a seasonal influenza vaccine which will also be administered with Advax-CpG adjuvant via the oral route. This study will use a cross-over design and everyone in the study will over a space of about 4 months receive both the COVID-19 and influenza vaccines.

Detailed description: 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. SARS-COV-2 vaccines remain a key priority to help fight the current pandemic as they help reduce symptomatic infection and disease severity. However, vaccine immunity starts to wane as early as 3 months following the most recent immunisation. This rapidly waning vaccine immunity is a particular problem for the newer Omicron variants. Spikogen® vaccine is an Advax-CpG55.2 adjuvanted recombinant protein vaccine that was shown to significantly reduce infection and serious disease in a pivotal Phase 3 trial in 16,876 participants who received two intramuscular doses 3 weeks apart. SpikoGen® vaccine was licensed for use in the Middle East as a primary vaccine course in adults in October 2021. Eight million doses of SpikoGen® vaccine have subsequently been supplied to date. A booster study confirmed the safety and immunogenicity of SpikoGen® vaccine when given as a third dose intramuscular booster to adult participants who previously received two doses of either inactivated viral vaccine, adenoviral vector vaccine, mRNA or recombinant protein vaccine. While COVID-19 vaccines such as SpikoGen® vaccine have been shown to reduce the incidence of severe SARS-CoV-2 infection disease, they have less effect on SARS-CoV-2 infection or transmission. This is because intramuscular vaccines largely work by increasing antibody and T cell levels within the body, whereas what is needed to prevent infection and transmission is mucosal immunity, which means increasing immunity at the body surfaces where the virus initially gets access to the body, namely the mucosal surfaces of the nose and upper respiratory tract. To induce mucosal immunity normally requires immune cells at these respiratory tract surfaces to be exposed to the relevant viral antigen, which requires the vaccine to be applied to these surfaces in such a way as to trigger an appropriate immune response.The current study is based on the finding that an adjuvanted protein-based COVID-19 vaccine (SpikoGen®) when given as 2 sublingual doses 2 weeks apart in monkeys that had previously received a primary course of 2 intramuscular doses of the same vaccine, was safe and well tolerated and induced robust protection against challenge with the heterologous Omicron BA.5 virus. The monkeys that received the sublingual boost also showed reduced nasal virus shedding (additional details in the Investigator Brochure). This suggests an oral/ sublingual COVID-19 vaccine may also help block virus transmission. Similarly, mice that received sublingual inactivated influenza vaccine with Advax-CpG adjuvant have demonstrated robust protection against an otherwise lethal influenza infection. The purpose of the current study is to assess the effectiveness of protein-based COVID-19 or influenza vaccines when given individually or together via oral/ sublingual mucosal route instead of intramuscular delivery. The comparator will be a seasonal influenza vaccine which will also be administered with Advax-CpG adjuvant via the oral route. This study will use a cross-over design and everyone in the study will over a space of about 4 months receive both the COVID-19 and influenza vaccines.

Eligibility criteria: 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.
* Do not plan to have a non-study COVID-19 or influenza vaccine within the next 6 months.

Exclusion Criteria:

* Allergy to COVID-19 or seasonal influenza vaccine or one of its components e.g. polysorbate 80.
* Have received a COVID-19 or influenza vaccine or an experimental agent within 30 days prior to the study vaccination or expect to receive another experimental agent or a COVID-19 or influenza vaccine during the trial reporting period.
* Any serious medical, social or mental condition which, in the opinion of the investigator, would be detrimental to the subjects or the study.

Primary outcomes:
measure: SARS-CoV-2 Seroconversion
timeFrame: Between baseline and 2 weeks post the second dose
measure: Influenza Seroconversion
timeFrame: Between baseline and 2 weeks post the second dose
measure: SARS-CoV-2 Seroprotection
timeFrame: Between baseline and 2 weeks post the second dose
measure: Influenza Seroprotection
timeFrame: Between baseline and 2 weeks post the second dose
measure: SARS-CoV-2 Geometric mean titer fold change
timeFrame: Between baseline and 2 weeks post the second dose
measure: Influenza geometric mean titer fold change
timeFrame: Between baseline and 2 weeks post the second dose
measure: Safety assessment 1
timeFrame: Between time of administration of first dose and through study completion, an average of 10 months
measure: Safety assessment 2
timeFrame: Between time of administration of first dose and through study completion, an average of 10 months
measure: SARS-CoV-2 infection
timeFrame: From 2 weeks post the administration of the second dose and through study completion, an average of 10 months
measure: Influenza infection
timeFrame: From 2 weeks post the administration of the second dose and through study completion, an average of 10 months
Secondary outcomes:
measure: Antibody durability
timeFrame: From 2 weeks post the administration of the second dose and through study completion, an average of 10 months
measure: Seroconversion in participants with and without evidence of past infection
timeFrame: From 2 weeks post the administration of the second dose and through study completion, an average of 10 months
measure: Antibody GMT in participants with and without evidence of past infection
timeFrame: From 2 weeks post the administration of the second dose and through study completion, an average of 10 months
measure: Antibody correlates of protection
timeFrame: From 2 weeks post the administration of the second dose and through study completion, an average of 10 months
Other outcomes:
Locations:
city: Adelaide
country: Australia
facility: ARASMI
state: South Australia
Study officials:
affiliation: ARASMI
name: Dimitar Sajkov, MBBS/PhD
role: PRINCIPAL_INVESTIGATOR
References: