Influenza, AvianPhase 1FLU007NCT03038776
Recombinant H7 Hemagglutinin Influenza Vaccine Trial
A Phase 1 study testing Recombinant influenza hemagglutinin in people with Influenza, Avian, run by Vaxine Pty Ltd at 1 site in Australia.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Influenza, Avian
- What is being tested?
- Recombinant influenza hemagglutinin
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 150 participants
- Where
- 1 siteAustralia
- Study dates
- Jan 2017to May 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomised, Controlled, Phase 1 Study in Healthy Adults to Evaluate the Immunogenicity and Safety of a Recombinant H7 Hemagglutinin Influenza Vaccine
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
Read the 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.
- Conditions
- Influenza, Avian
- Being tested
- Recombinant influenza hemagglutinin
- Keywords
- vaccine
- Medical subject headings
- Influenza in Birds
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Recombinant influenza hemagglutininBiological
Also called Panblok-H7
Avian H7N9 influenza vaccine
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Two i.m. administrations 4 weeks apart of recombinant influenza hemagglutinin corresponding to avian H7N9 virus strain (rH7 antigen) Receives: Biological: Recombinant influenza hemagglutinin |
| 2 | Experimental | Two i.m. administrations 4 weeks apart of recombinant influenza hemagglutinin corresponding to avian H7N9 virus strain (rH7 antigen) + Advax-1 adjuvant Receives: Biological: Recombinant influenza hemagglutinin |
| 3 | Experimental | Two i.m. administrations 4 weeks apart of recombinant influenza hemagglutinin corresponding to avian H7N9 virus strain (rH7 antigen) + Advax-2 adjuvant Receives: Biological: Recombinant influenza hemagglutinin |
| 4 | Experimental | Two i.m. administrations 4 weeks apart of T cell epitope modified recombinant influenza hemagglutinin corresponding to avian H7N9 virus strain (rH7m antigen) antigen Receives: Biological: Recombinant influenza hemagglutinin |
| 5 | Experimental | Two i.m. administrations 4 weeks apart of T cell epitope modified recombinant influenza hemagglutinin corresponding to avian H7N9 virus strain (rH7m antigen) + Advax-1 adjuvant Receives: Biological: Recombinant influenza hemagglutinin |
| 6 | Experimental | Two i.m. administrations 4 weeks apart of T cell epitope modified recombinant influenza hemagglutinin corresponding to avian H7N9 virus strain (rH7m antigen) + Advax-2 adjuvant Receives: Biological: Recombinant influenza hemagglutinin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Seroconversion
Measured: 1 month post immunization
Seroprotection
Measured: 1 month post immunization
Fold rise in geometric mean titer
Measured: 1 month post immunization
Secondary outcomes (2)
Safety: Frequency and severity of adverse events
Frequency and severity of adverse events
Measured: 12 months post immunization
T cell response
Frequency of influenza specific T cells
Measured: 1 month post-immunization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Feb 2017 (estimated)
- Study startJan 2017
- Primary completionNov 2017
- Study completionMay 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Influenza, AvianStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Vaxine Pty Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Australian Respiratory and Sleep Medicine Institute
- Responsible party
- Sponsor
- Investigators
- Dimitar Sajkov, MD, PhD, Principal investigator, Flinders University/ARASMI
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03038776
- Sponsor's protocol ID
- FLU007
- Acronym
- FLU007
- Status last verified
- May 2019
- First submitted
- 30 Jan 2017
- Last updated
- 7 May 2019
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised, Controlled, Phase 1 Study in Healthy Adults to Evaluate the Immunogenicity and Safety of a Recombinant H7 Hemagglutinin Influenza Vaccine
- ClinicalTrials.gov ID
- NCT03038776
- Acronym / sponsor ID
- FLU007 / FLU007
- Conditions
- Influenza, Avian
- Keywords
- vaccine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- Vaxine Pty LtdIndustry (pharma, biotech, devices)
- Collaborators
- Australian Respiratory and Sleep Medicine Institute
- Study start
- Jan 2017 (actual)
- Primary completion
- Nov 2017 (actual)
- Study completion
- May 2019 (actual)
- First posted
- 1 Feb 2017 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Biological: Recombinant influenza hemagglutininTwo i.m. administrations 4 weeks apart of recombinant influenza hemagglutinin corresponding to avian H7N9 virus strain (rH7 antigen) |
| 2 | Experimental | Biological: Recombinant influenza hemagglutininTwo i.m. administrations 4 weeks apart of recombinant influenza hemagglutinin corresponding to avian H7N9 virus strain (rH7 antigen) + Advax-1 adjuvant |
| 3 | Experimental | Biological: Recombinant influenza hemagglutininTwo i.m. administrations 4 weeks apart of recombinant influenza hemagglutinin corresponding to avian H7N9 virus strain (rH7 antigen) + Advax-2 adjuvant |
| 4 | Experimental | Biological: Recombinant influenza hemagglutininTwo i.m. administrations 4 weeks apart of T cell epitope modified recombinant influenza hemagglutinin corresponding to avian H7N9 virus strain (rH7m antigen) antigen |
| 5 | Experimental | Biological: Recombinant influenza hemagglutininTwo i.m. administrations 4 weeks apart of T cell epitope modified recombinant influenza hemagglutinin corresponding to avian H7N9 virus strain (rH7m antigen) + Advax-1 adjuvant |
| 6 | Experimental | Biological: Recombinant influenza hemagglutininTwo i.m. administrations 4 weeks apart of T cell epitope modified recombinant influenza hemagglutinin corresponding to avian H7N9 virus strain (rH7m antigen) + Advax-2 adjuvant |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Recombinant influenza hemagglutininAlso: Panblok-H7Avian H7N9 influenza vaccine | Biological | 1, 2, 3, 4, 5, 6 |
Primary outcome
Seroconversion
Time frame: 1 month post immunization
Seroprotection
Time frame: 1 month post immunization
Fold rise in geometric mean titer
Time frame: 1 month post immunization
2 secondary outcomes
Safety: Frequency and severity of adverse events
Time frame: 12 months post immunization
T cell response
Time frame: 1 month post-immunization
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 May 2019.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dimitar Sajkov, MD, PhD principal investigator
Flinders University/ARASMI
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Recombinant influenza hemagglutinin in people with Influenza, Avian, run by Vaxine Pty Ltd at 1 site in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 May 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Seroconversion (time frame: 1 month post immunization). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 May 2019.