Clinical trial NCT03038776: Recombinant H7 Hemagglutinin Influenza Vaccine Trial
Official title: A Randomised, Controlled, Phase 1 Study in Healthy Adults to Evaluate the Immunogenicity and Safety of a Recombinant H7 Hemagglutinin Influenza Vaccine
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Influenza, Avian
Keywords: vaccine
Lead sponsor: Vaxine Pty Ltd
Sponsor class: INDUSTRY
Collaborators: name: Australian Respiratory and Sleep Medicine Institute
First posted: 2017-02-01
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Recombinant H7 (rH7) vaccine has been shown to be poorly immunogenic in previous human clinical trials. This study will test approaches to improve the immunogenicity of H7 vaccine, namely use of a three dose regimen, use of a modified H7 HA sequence from which the Tregitope has been removed (rH7m), and inclusion of delta inulin adjuvant adjuvant in the vaccine

Detailed description: Because antibody responses to experimental H7 vaccine have been low even with high antigen doses, there is a need to find ways to enhance the effectiveness of H7 vaccines. Protein Sciences Corporation (PSC) produces an FDA approved seasonal recombinant trivalent influenza vaccine consisting of influenza hemagglutinin proteins (HA) which are full length uncleaved glycoproteins (rHA0) produced using baculovirus expression vectors in cultured insect cells grown in serum-free media (FluBlok®). The mechanism of action of FluBlok is the same as that of traditional inactivated seasonal influenza vaccines.

PanBlok H7 is a pandemic influenza vaccine produced by PSC in the same way as Flublok but it is directed against H7 rather than seasonal influenza virus strains. The vaccine candidate consists of a full-length recombinant monovalent hemagglutinin (rHA) derived from H7N9 virus, in a sterile solution for intramuscular injection. PanBlok H7 rHA is manufactured using the same production process as previously used for Panblok H1/2009pdm ("swine flu") and Panblok H5 pandemic vaccines, both of which vaccines have been previously successfully trialled by us in clinical protocols, FLU005 and FLU003. In both these trials the Panblok antigen was combined with Advax adjuvant formulations. In the FLU005 trial of Panblok H1N1/2009pdm vaccine, the inclusion of Advax adjuvant doubled the seroconversion rate of the vaccine and provided major antigen-sparing effects (Gordon et al, 2012). Whilst the FLU003 trial is ongoing, preliminary data again shows the importance of the Advax adjuvants to vaccine effectiveness. This provides a strong rationale for inclusion of Advax adjuvants in the Panblok H7 vaccine.

It has also been recently recognised that at least one of the reasons for the low immunogenicity of H7 vaccines in human trials to date is that the H7 antigen from this virus contains a T-cell regulatory epitope (Tregitope) in the HA stem region which suppresses the immune response to the vaccine. It was recently demonstrated in humanised animal studies undertaken by collaborators in Japan that removing this Tregitope by modifying 3 amino acids in the H7 stem was able to significantly increase the ability of the H7 vaccine to induce antibody production by human immune cells. This trial will provide the first opportunity to confirm this approach is able to enhance the immunogenicity of H7 in humans, which if confirmed would represent a major breakthough in pandemic influenza vaccine design.

Eligibility criteria: Inclusion Criteria:

* Male or female
* Age 18 years or over
* Able to provide written informed consent
* Willing and able to comply with the protocol for the duration of the study

Exclusion Criteria:

* History of serious vaccine allergy\*
* History of vasculitis, Wegener's granulomatosis, narcolepsy, Guillain Barre, SLE or other systemic autoimmune disease that in the opinion of the investigator would make the vaccine contraindicated
* History of chronic liver disease or liver transaminases elevated more than 3xULN
* Women of childbearing potential, unless using a reliable and appropriate contraceptive method, specifically oral contraceptive pill, IUD or mechanical barrier device.
* Pregnant or lactating women.
* Any serious medical, social or mental condition which, in the opinion of the investigator, would be detrimental to the subjects or the study.
* Receipt of another investigational agent within 28 days preceding initiation of treatment.

  * Individuals who have a past history of potential vaccine reactions will be assessed by the investigator, who will decide whether any past potential vaccine-related side are sufficiently minimal to allow vaccine administration to proceed.

Primary outcomes:
measure: Seroconversion
timeFrame: 1 month post immunization
measure: Seroprotection
timeFrame: 1 month post immunization
measure: Fold rise in geometric mean titer
timeFrame: 1 month post immunization
Secondary outcomes:
measure: Safety: Frequency and severity of adverse events
timeFrame: 12 months post immunization
measure: T cell response
timeFrame: 1 month post-immunization
Other outcomes:
Locations:
city: Adelaide
country: Australia
facility: Flinders University
state: South Australia
Study officials:
affiliation: Flinders University/ARASMI
name: Dimitar Sajkov, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: