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H7HLAII DNA Influenza Vaccine (H7N9vax-1)

Primary Purpose

Influenza A, Pandemic Influenza

Status
Recruiting
Phase
Phase 1
Locations
Norway
Study Type
Interventional
Intervention
H7HLAII
Sponsored by
Oslo University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Influenza A

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: 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. Exclusion Criteria: 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 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

Sites / Locations

  • Oslo University HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Vaccinated

Arm Description

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.

Outcomes

Primary Outcome Measures

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.
Abnormalities in physical examination, vital signs, and clinical laboratory tests
Number of participants with aberrant results.

Secondary Outcome Measures

Changes in virus neutralization assay titres relative to baseline
geometric mean titres
Changes in anti-H7 antibody levels relative to baseline
seroconversion rates

Full Information

First Posted
September 3, 2023
Last Updated
September 20, 2023
Sponsor
Oslo University Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT06046092
Brief Title
H7HLAII DNA Influenza Vaccine
Acronym
H7N9vax-1
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 15, 2023 (Actual)
Primary Completion Date
December 31, 2024 (Anticipated)
Study Completion Date
December 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Oslo University Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief 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 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Influenza A, Pandemic Influenza

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Model Description
Open label, single arm dose escalation phase I trial
Masking
None (Open Label)
Allocation
N/A
Enrollment
27 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Vaccinated
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
H7HLAII
Intervention Description
DNA vaccine encoding influenza hemagglutinin (HA) from influenza A/Shanghai/2/2013 (H7N9) directed to cells expressing human leukocyte antigen class II (HLAII) molecules
Primary Outcome Measure Information:
Title
Solicited adverse events following vaccination
Description
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.
Time Frame
10 days
Title
Abnormalities in physical examination, vital signs, and clinical laboratory tests
Description
Number of participants with aberrant results.
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Changes in virus neutralization assay titres relative to baseline
Description
geometric mean titres
Time Frame
6 months
Title
Changes in anti-H7 antibody levels relative to baseline
Description
seroconversion rates
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Gunnveig Grødeland, PhD
Phone
47 41667705
Email
Gunnveig.Grodeland@medisin.uio.no
First Name & Middle Initial & Last Name or Official Title & Degree
Dag Kvale, MD/PhD
Phone
+4795200709
Email
Dag.Kvale@medisin.uio.no
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dag Kvale, MSc/PhD
Organizational Affiliation
Oslo University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Oslo University Hospital
City
Oslo
ZIP/Postal Code
0372
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gunnveig Grødeland, PhD
Phone
4741667704
Email
gunnveig.grodeland@medisin.uio.no
First Name & Middle Initial & Last Name & Degree
Dag Kvale, MD/PhD
Phone
+4795200709
Email
Dag.Kvale@medisin.uio.no

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
27671110
Citation
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.
Results Reference
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H7HLAII DNA Influenza Vaccine

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