Influenza APhase 1H7N9vax-1NCT06046092
H7HLAII DNA Influenza Vaccine
A Phase 1 study testing H7HLAII in people with Influenza A and Pandemic Influenza, run by Oslo University Hospital at 1 site in Norway.
Trial summary
The purpose of this study is to assess safety and immunogenicity of H7HLAII, a DNA vaccine encoding influenza hemagglutinin (HA) from influenza A/Shanghai/2/2013 (H7N9) directed to cells expressing human leukocyte antigen class II (HLAII) molecules, for prophylaxis of pandemic H7N9 influenza infection in healthy… Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Influenza A, Pandemic Influenza
- What is being tested?
- H7HLAII
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 1 siteNorway
- Study dates
- 15 Jul 2023to 31 Dec 2024
- 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 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy subjects, as concluded from the medical history, physical examination test including normal vital signs, and clinical judgment, without the need for medication.
- For women with childbearing potential (WOCBP), defined as fertile following menarche and until becoming post-menopausal (i.e. no menses for 12 months without an alternative medical cause) unless permanently sterile by hysterectomy, bilateral salpingectomy and bilateral oophorectomy: Must use a highly effective contraceptive measures (from 4 weeks prior to the first vaccination until 4 weeks after the second vaccination), and a negative urine pregnancy test before administration of each dose of vaccine. Must agree to not donate eggs during the study and the first three months after their last study visit.
- Able to understand and willing to sign the Informed Consent Form (ICF), which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
- Subjects able to understand and comply with the study protocol, including being able to attend the scheduled visits.
Who cannot join
- Medical Conditions
- Ongoing or recent (< 2 weeks) intercurrent febrile condition
- Previous reports of autoimmune disease
- Concurrent chronic active viral hepatitis B or C or HIV
- BMI>30
- Persons with a history of anaphylaxis or serious reactions to a prior vaccination
Show all 15Show fewer
- Persons with known hypersensitivity to any of the vaccine components
- Persons who have had a temperature >38 °C during the previous 72 hours
- Persons who have had an acute respiratory infection during the last 7 days
- Persons who have abnormal electrocardiogram (ECG)
- Women who are pregnant or breast-feeding (women of child-bearing potential must have a negative pregnancy test at screening)
- Have received any vaccination within the last month
- Prior/Concomitant Therapy 12. Currently taking anti-inflammatory or immunosuppressive drugs 13. Currently taking antibiotics, steroids, phenytoin, chemotherapy, or other immunosuppressive drugs
- Prior/Concurrent Clinical Study Experience 14. Persons who have participated in another clinical trial during the last month
- Diagnostic assessments 15. Abnormal values of the hematologic and clinical chemistry parameters, as judged by the Investigator, including creatinine, AST, ALT (SGPT), bilirubin and alkaline phosphatase values above normal reference values 16. Positive autoantibodies (anti-nuclear antigens, rheumatoid factor) 17. Serum IgG and IgM lower or higher than the normal reference levels 18. Positive serology tests for hepatitis B or C with detectable hepatitis B HBsAg or DNA, or hepatitis C RNA 19. Positive HIV serology test
Trial locations and contacts
1 site in 1 country.
Norway1 site, 1 recruiting
- Recruiting
Oslo University Hospital
Oslo, 0372
Gunnveig Grødeland, PhD, 4741667704, gunnveig.grodeland@medisin.uio.no
Dag Kvale, MD/PhD, +4795200709, Dag.Kvale@medisin.uio.no
About this study
Official title: An Open Label, Dose Escalation Phase I Trial to Assess Safety and Immunogenicity of the H7HLAII DNA Vaccine, Encoding Influenza Hemagglutinin H7 Directed to HLA Class II, for Prophylaxis of Pandemic Influenza Infection in Healthy Volunteers
The purpose of this study is to assess safety and immunogenicity of H7HLAII, a DNA vaccine encoding influenza hemagglutinin (HA) from influenza A/Shanghai/2/2013 (H7N9) directed to cells expressing human leukocyte antigen class II (HLAII) molecules, for prophylaxis of pandemic H7N9 influenza infection in healthy volunteers.
Read the detailed description
H7HLAII is a DNA vaccine that could remedy the current challenges of slow production for conventional influenza vaccines. The prolonged production time of current influenza vaccines has as a consequence that circulating influenza strains often have drifted significantly from the vaccine included strains, and as such reducing vaccine efficacy. The rapid production enabled by the DNA format could enhance efficacy of seasonal influenza vaccines, but is particularly well suited for prophylaxis against an emerging influenza pandemic.
The only vaccine format that can presently be produced and deployed within 2-3 months is DNA. However, DNA vaccines are typically hampered by low immunogenicity. To surpass this challenge, H7HLAII genetically links the influenza H7 HA to a targeting unit that steers the produced vaccine proteins to HLA class II expressing antigen presenting cells (APC). Previously, this strategy has been shown to increase immunogenicity after vaccination in mice, ferrets, pigs, and rhesus macaques, with a particular strength in antibody induction. Of note, antibodies represent a correlate of protection against influenza, as well as most other infectious diseases. It has also been shown that H7HLAII protected immunized ferrets against a homologous H7N9 strain, and with no safety concerns after toxicity testing in guinea pigs.
H7HLAII is designed to induce strong antibody responses against a specific strain of H7N9 influenza. At present, there are several strains of H7N9 that cause concern for future pandemic emergences, in that periodic zoonotic transmissions are observed in Asia. To date, H7N9 viruses do not have the ability to transmit between humans, but the high mortality rates observed after zoonotic transmissions dictates that society ought to be ready for future emergences. H7HLAII is designed to enable rapid exchange of antigen, allowing for accommodation of any HA into the vaccine construct. As such, the strategy could be of great importance for global prophylactic prevention.
Although a pandemic situation might opt for rapid testing, this trial is planned as a cautious phase I trial with healthy volunteers. It should be noted that the safety aspects for a number of DNA vaccines has been good during clinical testing over the past decade, and the first DNA vaccine was recently licensed for human use.
- Conditions
- Influenza A, Pandemic Influenza
- Being tested
- H7HLAII
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
H7HLAIIBiological
DNA vaccine encoding influenza hemagglutinin (HA) from influenza A/Shanghai/2/2013 (H7N9) directed to cells expressing human leukocyte antigen class II (HLAII) molecules
| Study group | Role | What they receive |
|---|---|---|
| Vaccinated | Experimental | Participants will be allocated to one of 3 dose groups, each receiving two intradermal (i.d.) vaccinations with 0.12 mg, 0.60 mg, or 3.00 mg of H7HLAII, respectively. Receives: Biological: H7HLAII |
What is being measured
The primary outcome is the main question the study is designed to answer.
Solicited adverse events following vaccination
Solicited injection site reactions: Redness, Swelling, Pain, Erythema, and Induration; Solicited systemic reactions: Fever, Sweating, Chill, Nausea, Diarrhea, Headache, Fatigue, Myalgia, Arthralgia, and Respiratory symptoms.
Measured: 10 days
Abnormalities in physical examination, vital signs, and clinical laboratory tests
Number of participants with aberrant results.
Measured: 6 months
Secondary outcomes (2)
Changes in virus neutralization assay titres relative to baseline
geometric mean titres
Measured: 6 months
Changes in anti-H7 antibody levels relative to baseline
seroconversion rates
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2023
- Study start15 Jul 2023
- Primary completion31 Dec 2024 (estimated)
- Study completion31 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Influenza AStudies of the same condition, open and under way.
- More trials run by Oslo University HospitalThe sponsor's other registered studies.
- 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
- Not applicable
- Intervention model
- Sequential
- Model description
- Open label, single arm dose escalation phase I trial
- Masking
- None (open label)
- Enrolment
- 27 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Oslo University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Gunnveig Grødeland, Oslo University Hospital
- Investigators
- Dag Kvale, MSc/PhD, Principal investigator, Oslo University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06046092
- Sponsor's protocol ID
- 2022-500706-18-01
- Acronym
- H7N9vax-1
- Status last verified
- Sep 2023
- First submitted
- 3 Sep 2023
- Last updated
- 22 Sep 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Grodeland G, Fredriksen AB, Loset GA, Vikse E, Fugger L, Bogen B. Antigen Targeting to Human HLA Class II Molecules Increases Efficacy of DNA Vaccination. J Immunol. 2016 Nov 1;197(9):3575-3585. doi: 10.4049/jimmunol.1600893. Epub 2016 Sep 26.
PubMed 27671110
Study at a glance
From the registry record, last updated by the sponsor on 22 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label, Dose Escalation Phase I Trial to Assess Safety and Immunogenicity of the H7HLAII DNA Vaccine, Encoding Influenza Hemagglutinin H7 Directed to HLA Class II, for Prophylaxis of Pandemic Influenza Infection in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT06046092
- Acronym / sponsor ID
- H7N9vax-1 / 2022-500706-18-01
- Conditions
- Influenza A, Pandemic Influenza
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 27 participants (estimated)
- Lead sponsor
- Oslo University HospitalUniversity, hospital or other
- Study start
- 15 Jul 2023 (actual)
- Primary completion
- 31 Dec 2024 (estimated)
- Study completion
- 31 Dec 2024 (estimated)
- First posted
- 21 Sep 2023 (actual)
- 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.
The purpose of this study is to assess safety and immunogenicity of H7HLAII, a DNA vaccine encoding influenza hemagglutinin (HA) from influenza A/Shanghai/2/2013 (H7N9) directed to cells expressing human leukocyte antigen class II (HLAII) molecules, for prophylaxis of pandemic H7N9 influenza infection in healthy volunteers.
Detailed description
H7HLAII is a DNA vaccine that could remedy the current challenges of slow production for conventional influenza vaccines. The prolonged production time of current influenza vaccines has as a consequence that circulating influenza strains often have drifted significantly from the vaccine included strains, and as such reducing vaccine efficacy. The rapid production enabled by the DNA format could enhance efficacy of seasonal influenza vaccines, but is particularly well suited for prophylaxis against an emerging influenza pandemic.
The only vaccine format that can presently be produced and deployed within 2-3 months is DNA. However, DNA vaccines are typically hampered by low immunogenicity. To surpass this challenge, H7HLAII genetically links the influenza H7 HA to a targeting unit that steers the produced vaccine proteins to HLA class II expressing antigen presenting cells (APC). Previously, this strategy has been shown to increase immunogenicity after vaccination in mice, ferrets, pigs, and rhesus macaques, with a particular strength in antibody induction. Of note, antibodies represent a correlate of protection against influenza, as well as most other infectious diseases. It has also been shown that H7HLAII protected immunized ferrets against a homologous H7N9 strain, and with no safety concerns after toxicity testing in guinea pigs.
H7HLAII is designed to induce strong antibody responses against a specific strain of H7N9 influenza. At present, there are several strains of H7N9 that cause concern for future pandemic emergences, in that periodic zoonotic transmissions are observed in Asia. To date, H7N9 viruses do not have the ability to transmit between humans, but the high mortality rates observed after zoonotic transmissions dictates that society ought to be ready for future emergences. H7HLAII is designed to enable rapid exchange of antigen, allowing for accommodation of any HA into the vaccine construct. As such, the strategy could be of great importance for global prophylactic prevention.
Although a pandemic situation might opt for rapid testing, this trial is planned as a cautious phase I trial with healthy volunteers. It should be noted that the safety aspects for a number of DNA vaccines has been good during clinical testing over the past decade, and the first DNA vaccine was recently licensed for human use.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Open label, single arm dose escalation phase I trial
| Arm | Type | Receives |
|---|---|---|
| Vaccinated | Experimental | Biological: H7HLAIIParticipants will be allocated to one of 3 dose groups, each receiving two intradermal (i.d.) vaccinations with 0.12 mg, 0.60 mg, or 3.00 mg of H7HLAII, respectively. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Healthy subjects, as concluded from the medical history, physical examination test including normal vital signs, and clinical judgment, without the need for medication.
- For women with childbearing potential (WOCBP), defined as fertile following menarche and until becoming post-menopausal (i.e. no menses for 12 months without an alternative medical cause) unless permanently sterile by hysterectomy, bilateral salpingectomy and bilateral oophorectomy: Must use a highly effective contraceptive measures (from 4 weeks prior to the first vaccination until 4 weeks after the second vaccination), and a negative urine pregnancy test before administration of each dose of vaccine. Must agree to not donate eggs during the study and the first three months after their last study visit.
- Able to understand and willing to sign the Informed Consent Form (ICF), which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
- Subjects able to understand and comply with the study protocol, including being able to attend the scheduled visits.
Key exclusion criteria (15 listed)
- Medical Conditions
- Prior/Concomitant Therapy 12. Currently taking anti-inflammatory or immunosuppressive drugs 13. Currently taking antibiotics, steroids, phenytoin, chemotherapy, or other immunosuppressive drugs
- Prior/Concurrent Clinical Study Experience 14. Persons who have participated in another clinical trial during the last month
- Diagnostic assessments 15. Abnormal values of the hematologic and clinical chemistry parameters, as judged by the Investigator, including creatinine, AST, ALT (SGPT), bilirubin and alkaline phosphatase values above normal reference values 16. Positive autoantibodies (anti-nuclear antigens, rheumatoid factor) 17. Serum IgG and IgM lower or higher than the normal reference levels 18. Positive serology tests for hepatitis B or C with detectable hepatitis B HBsAg or DNA, or hepatitis C RNA 19. Positive HIV serology test
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 |
|---|---|---|
| H7HLAIIDNA vaccine encoding influenza hemagglutinin (HA) from influenza A/Shanghai/2/2013 (H7N9) directed to cells expressing human leukocyte antigen class II (HLAII) molecules | Biological | Vaccinated |
Primary outcome
Solicited adverse events following vaccination
Time frame: 10 days
Solicited injection site reactions: Redness, Swelling, Pain, Erythema, and Induration; Solicited systemic reactions: Fever, Sweating, Chill, Nausea, Diarrhea, Headache, Fatigue, Myalgia, Arthralgia, and Respiratory symptoms.
Abnormalities in physical examination, vital signs, and clinical laboratory tests
Time frame: 6 months
Number of participants with aberrant results.
2 secondary outcomes
Changes in virus neutralization assay titres relative to baseline
Time frame: 6 months
Changes in anti-H7 antibody levels relative to baseline
Time frame: 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Sep 2023.
- Background: PubMed 27671110Grodeland G, Fredriksen AB, Loset GA, Vikse E, Fugger L, Bogen B. Antigen Targeting to Human HLA Class II Molecules Increases Efficacy of DNA Vaccination. J Immunol. 2016 Nov 1;197(9):3575-3585. doi: 10.4049/jimmunol.1600893. Epub 2016 Sep 26.
- Individual participant dataSharing planned: No
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Healthy Participants
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.
Dag Kvale, MSc/PhD principal investigator
Oslo University Hospital
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 H7HLAII in people with Influenza A and Pandemic Influenza, run by Oslo University Hospital at 1 site in Norway.
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 15 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: status not confirmed, as of the sponsor's last update on 22 Sep 2023. 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 Norway. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Gunnveig Grødeland, PhD (47 41667705, Gunnveig.Grodeland@medisin.uio.no), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Solicited adverse events following vaccination (time frame: 10 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06046092, which also lists 1 linked publication.
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 22 Sep 2023.