Covid-19 and Influenza Oral Vaccine Study

Influenza, Human Clinical Trial

Official title:

A Binded, Randomised, Controlled Cross-over Trial to Assess the Safety and Efficacy of Mucosal Covid-19 and Influenza Vaccines

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06355232
• Other study ID #: Vaxine-2301
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: April 21, 2024
• Est. completion date: April 21, 2025

Study information

• Verified date: April 2024
• Source: Vaxine Pty Ltd
• Contact: Sharen Pringle, GradCert
• Phone: 0437033400
• Email: office[@]arasmi.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 100
• Est. completion date: April 21, 2025
• Est. primary completion date: April 21, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• COVID-19
• covid19 Infection
• Influenza, Human

Intervention

Biological:
• Covid-19 vaccine
Recombinant SARS-CoV-2 spike protein with Advax-CpG55.2 adjuvant
• Influenza vaccine
Inactivated seasonal influenza vaccine with Advax-CpG55.2 adjuvant

Locations

Country	Name	City	State
Australia	ARASMI	Adelaide	South Australia

Sponsors (2)

Lead Sponsor	Collaborator
Vaxine Pty Ltd	Australian Respiratory and Sleep Medicine Institute Ltd

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	SARS-CoV-2 Seroconversion	Proportion of study participants who seroconvert (4-fold or greater rise in serum spike antibody) by primary vaccine group	Between baseline and 2 weeks post the second dose
Primary	Influenza Seroconversion	Proportion of study participants who seroconvert (4-fold or greater rise in hemagglutinin antibody) by primary vaccine group	Between baseline and 2 weeks post the second dose
Primary	SARS-CoV-2 Seroprotection	Proportion of study participants who achieve a spike protein neutralisation titer of 32 or greater by primary vaccine group	Between baseline and 2 weeks post the second dose
Primary	Influenza Seroprotection	Proportion of study participants who achieve a hemagglutinin neutralisation titer of 40 or greater by primary vaccine group	Between baseline and 2 weeks post the second dose
Primary	SARS-CoV-2 Geometric mean titer fold change	Increase in Geometric mean titer of spike neutralisation antibodies by primary vaccine group	Between baseline and 2 weeks post the second dose
Primary	Influenza geometric mean titer fold change	Increase in Geometric mean titer of spike neutralisation antibodies by primary vaccine group	Between baseline and 2 weeks post the second dose
Primary	Safety assessment 1	Frequency of Adverse events by primary vaccine group	Between time of administration of first dose and through study completion, an average of 10 months
Primary	Safety assessment 2	Frequency of Serious Adverse events by primary vaccine group	Between time of administration of first dose and through study completion, an average of 10 months
Primary	SARS-CoV-2 infection	Frequency of SARS-CoV-2 infections in study participants by primary vaccine group, age, gender, co-morbidities, and past infection	From 2 weeks post the administration of the second dose and through study completion, an average of 10 months
Primary	Influenza infection	Frequency ofinfluenza infections in study participants by primary vaccine group, age, gender, co-morbidities, and past infection	From 2 weeks post the administration of the second dose and through study completion, an average of 10 months
Secondary	Antibody durability	The proportion of subjects who remain seroprotected throughout the duration of the study including broken down by primary vaccine group.	From 2 weeks post the administration of the second dose and through study completion, an average of 10 months
Secondary	Seroconversion in participants with and without evidence of past infection	Antibody seroconversion in participants by primary vaccine group	From 2 weeks post the administration of the second dose and through study completion, an average of 10 months
Secondary	Antibody GMT in participants with and without evidence of past infection	Antibody GMT in baseline seropositive versus negative participants by primary vaccine group.	From 2 weeks post the administration of the second dose and through study completion, an average of 10 months
Secondary	Antibody correlates of protection	antibody levels in subjects with or without breakthrough infection	From 2 weeks post the administration of the second dose and through study completion, an average of 10 months