A Phase 1 Study to Evaluate the Immunogenicity and Safety of a Pandemic Avian Influenza Vaccine in Adults

Study Overview
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Brief Summary
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Recombinant hemagglutinin has been shown to induce protective neutralising antibodies against avian influenza virus but is relatively non-immunogenic. An ideal pandemic avian influenza influenza vaccine would combine hemagglutinin antigen with an appropriate adjuvant to increase its immunogenicity. This Phase 1 study will collect preliminary human safety and efficacy data on combined formulations of recombinant hemagglutinin with Advax adjuvant formulations administered by intramuscular injection

Detailed Description
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This is a study to test new vaccine formulations against pandemic avian influenza (bird flu). Bird flu is a potentially deadly disease that is caused by influenza virus from birds. It is not the same as the common seasonal flu for which there is a seasonal vaccine released around March each year. To date, bird flu due to the H5N1 strain of influenza virus has infected over 500 people mainly in Asia resulting in death in more than half the cases. More recently there has been an outbreak of another bird flu virus in China known as H9N7 that is also highly lethal when it infects humans. Vaccination is the single most effective measure to prevent infection from bird flu viruses such as H5N1 or H9N7 should such a pandemic occur. In the event of a major bird flu pandemic outbreak, vaccine supplies are likely to be very limited, as there is not currently sufficient manufacturing capacity to provide enough vaccine quickly for the whole population. Research is needed on how to make the pandemic flu vaccine more effective but also how to stretch vaccine supplies using a strategy called 'antigen-sparing'. This can potentially be achieved by using an important ingredient called an 'adjuvant'. Adjuvants act by stimulating the immune system to make vaccines more effective. This study will test Advax adjuvants which are based on delta inulin in combination with recombinant hemagglutinin from the H5N1 influenza virus serotype.

Official Title
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A Randomised, Controlled, Blinded Phase 1 Study to Evaluate the Immunogenicity and Safety of a Pandemic Avian H5 Influenza Vaccine in Adults

Conditions
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Influenza

Intervention / Treatment
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* Biological: recombinant influenza hemagglutinin
* Biological: Advax1
* Biological: Advax2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ambulatory males or females aged 18 years and over Able to provide written informed consent Willing and able to comply with the protocol for the duration of the study. Not planning to have seasonal influenza vaccine within 2 months from the time of the first trial immunization Exclusion Criteria: Pregnant or lactating women. Women of childbearing potential unless using a reliable and appropriate contraceptive method. Receipt of another investigational agent within 28 days preceding initiation of treatment. Any other serious 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
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HA 45ug<br>recombinant influenza hemagglutinin (H5) 45ug, i.m. injection, 2 doses | Biological: recombinant influenza hemagglutinin<br>* recombinant influenza hemagglutinin<br>|
| Experimental: HA 45ug+Advax1<br>recombinant influenza hemagglutinin(H5) 45ug, Advax1 adjuvant 20mg, i.m. injection, 2 doses | Biological: recombinant influenza hemagglutinin<br>* recombinant influenza hemagglutinin<br>Biological: Advax1<br>* Delta inulin adjuvant formulation 1<br>|
| Experimental: HA 45ug+Advax2<br>recombinant influenza hemagglutinin (H5) 45ug, Advax2 adjuvant 20mg, i.m. injection, 2 doses | Biological: recombinant influenza hemagglutinin<br>* recombinant influenza hemagglutinin<br>Biological: Advax2<br>* Delta inulin adjuvant formulation 2<br>|
| Experimental: HA 15ug+Advax1<br>recombinant influenza hemagglutinin (H5) 15ug, Advax1 adjuvant 20mg, i.m. injection, 2 doses | Biological: recombinant influenza hemagglutinin<br>* recombinant influenza hemagglutinin<br>Biological: Advax1<br>* Delta inulin adjuvant formulation 1<br>|
| Experimental: HA 15ug+Advax2<br>recombinant influenza hemagglutinin (H5) 15ug, Advax2 adjuvant 20mg, i.m. injection, 2 doses | Biological: recombinant influenza hemagglutinin<br>* recombinant influenza hemagglutinin<br>Biological: Advax2<br>* Delta inulin adjuvant formulation 2<br>|
| Experimental: HA 5ug+Advax1<br>recombinant influenza hemagglutinin (H5) 5ug, Advax1 adjuvant 20mg, i.m. injection, 2 doses | Biological: recombinant influenza hemagglutinin<br>* recombinant influenza hemagglutinin<br>Biological: Advax1<br>* Delta inulin adjuvant formulation 1<br>|
| Experimental: HA 5ug+Advax2<br>recombinant influenza hemagglutinin (H5) 5ug, Advax2 adjuvant 20mg, i.m. injection, 2 doses | Biological: recombinant influenza hemagglutinin<br>* recombinant influenza hemagglutinin<br>Biological: Advax2<br>* Delta inulin adjuvant formulation 2<br>|
| Experimental: HA 2.5ug+Advax2<br>recombinant influenza hemagglutinin (H5) 2.5ug, Advax2 adjuvant 20mg, i.m. injection, 2 doses | Biological: recombinant influenza hemagglutinin<br>* recombinant influenza hemagglutinin<br>Biological: Advax2<br>* Delta inulin adjuvant formulation 2<br>|
| Experimental: HA 15ug<br>recombinant influenza hemagglutinin (H5) 15ug, i.m. injection, 2 doses | Biological: recombinant influenza hemagglutinin<br>* recombinant influenza hemagglutinin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of adverse events | The frequency of adverse events will be compared between groups | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hemagglutination inhibition assay | Seroconversion, seroprotection and GMT fold increase will be compared between groups at each time point using hemagglutination inhibition titers | 1 month post each immunization and 11 months post final immunization |