Evaluation of the Safety and Immunogenicity of a Recombinant Trivalent Nanoparticle Influenza Vaccine With Matrix M-1 Adjuvant (NanoFlu)
Study Details
Study Description
Brief Summary
This is a Phase 1/2, randomized, observer-blinded, active-controlled trial. Approximately 330 eligible subjects will be enrolled and randomized into 1 of 3 treatment groups as shown in the Trial Design table below. Each group will consist of approximately 110 subjects total, stratified by age, gender, and history of receipt of 2016 - 17 influenza vaccine. On Day 0, subjects in Groups A and B will be administered an IM injection of NanoFlu at one of two dose levels; subjects in Group C will receive the preconfigured comparator (Fluzone HD) at the manufacturer's recommended dose and volume. On Day 21, all Group A and B subjects will be administered a rescue injection with a licensed seasonal influenza vaccine, while all Group C subjects will be administered an injection with sterile saline placebo to maintain trial blind. Trial follow-up for each subject will span approximately 1 year from the Day 0.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Group A Low dose NanoFlu - Day 0; Fluzone HD - Day 21 |
Biological: NanoFlu
Vaccine
Biological: Fluzone HD - Day 21
Vaccine
|
| Experimental: Group B High dose NanoFlu - Day 0; Fluzone HD - Day 21 |
Biological: NanoFlu
Vaccine
Biological: Fluzone HD - Day 21
Vaccine
|
| Active Comparator: Group C Fluzone HD - Day 0; Saline - Day 21 |
Biological: Fluzone HD - Day 0
Vaccine
Other: Saline - Day 21
Placebo
|
Outcome Measures
Primary Outcome Measures
- Number and percentage of subjects adverse events. [Day 0 - Day 365]
Solicited local and systemic adverse events over the 7 days post-injection (ie, Day 0 through Day 6 post-dosing); all adverse events (including adverse changes in clinical laboratory parameters) through 21 days post-injection; and MAEs, SAEs, and SNMCs through 1 year post-Day 0 dosing.
- Geometric Mean Titers (GMT) specific for the HA receptor binding domains of each of the virus strains included in the NanoFlu as measured by the HAI assay. [Day 0 - Day 21]
- Geometric Mean Ratio (GMR) specific for the HA receptor binding domains of each of the virus strains included in the NanoFlu as measured by the HAI assay. [Day 0 - Day 21]
- Seroconversion Rate (SCR) specific for the HA receptor binding domains of each of the virus strains included in the NanoFlu as measured by the HAI assay. [Day 0 - Day 21]
- Seroconversion Rate differences specifically difference of seroconversion rates between each of the NanoFlu vaccine groups and the Fluzone HD group. [Day 0 - Day 21]
- Seroprotection Rate (SPR) specific for the HA receptor binding domains of each of the virus strains included in the NanoFlu as measured by the HAI assay. [Day 0 - Day 21]
Secondary Outcome Measures
- Geometric Mean Titers (GMT) specific for the HA receptor binding domains of at least 2 historic A virus strains (one H1N1 and one H3N2) as measured by the HAI assay [Day 0 - Day 21]
- Geometric Mean Ratio (GMR) specific for the HA receptor binding domains of at least 2 historic A virus strains (one H1N1 and one H3N2) as measured by the HAI assay [Day 0 - Day 21]
- Seroconversion Rate (SCR) specific for the HA receptor binding domains of at least 2 historic A virus strains (one H1N1 and one H3N2) as measured by the HAI assay [Day 0 - Day 21]
- Seroprotection Rate (SPR) specific for the HA receptor binding domains of at least 2 historic A virus strains (one H1N1 and one H3N2) as measured by the HAI assay [Day 0 - Day 21]
- Geometric Mean Titers (GMT) for neutralizing antibody titers specific for the virus strains included in NanoFlu and the Fluzone HD comparator, as well as selected historical A strains, as measured by a microneutralization assay. [Day 0 - Day 21]
- Geometric Mean Ratio (GMR) for neutralizing antibody titers specific for the virus strains included in NanoFlu and the Fluzone HD comparator, as well as selected historical A strains, as measured by a microneutralization assay. [Day 0 - Day 21]
- Seroconversion Rate (SCR) for neutralizing antibody titers specific for the virus strains included in NanoFlu and the Fluzone HD comparator, as well as selected historical A strains, as measured by a microneutralization assay. [Day 0 - Day 21]
Other Outcome Measures
- HAI and neutralizing antibody titers specific for a contemporary B/Yamagata virus strain. [Day 0 - Day 21]
- Levels of antibodies competitive with broadly-neutralizing monoclonal antibodies to HA of varying specificities, as measured by competitive-binding in a biosensor assay. [Day 0 - Day 21]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Healthy older adults, male or female,
-
Willing and able to give informed consent prior to trial enrollment, and
-
Able to attend trial visits, comply with trial requirements, and provide reliable and complete reports of adverse events.
Exclusion Criteria:
- Any ongoing, symptomatic acute or chronic illness requiring medical or surgical care.
-
Asymptomatic chronic conditions or findings (eg, mild hypertension, dyslipidemia) that are not associated with evidence of end-organ damage are not exclusionary provided that they are being appropriately managed and are clinically stable (ie, unlikely to result in symptomatic illness within the time-course of this trial) in the opinion of the investigator.
-
Acute or chronic illnesses or conditions which may be reasonably predicted to become symptomatic if treatment were withdrawn or interrupted are exclusionary, even if stable.
-
Acute or chronic illnesses reasonably expected to be associated with increased risks in the event of influenza infection (eg, cardio-pulmonary diseases, diabetes mellitus, renal or hepatic dysfunction, hemoglobinopathies) are exclusionary, even if stable.
-
Note that illnesses or conditions may be exclusionary, even if otherwise stable, due to therapies used to treat them (see exclusion criteria 2, 5, 8, 9).
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Participation in research involving investigational product (drug / biologic / device) within 45 days before planned date of first injection.
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History of a serious reaction to prior influenza vaccination, or known allergy to constituents of influenza vaccines - including egg proteins - or polysorbate 80.
-
History of Guillain-Barré Syndrome (GBS) within 6 weeks following a previous influenza vaccine.
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Receipt of any vaccine in the 4 weeks preceding the trial vaccination and any influenza vaccine within 6 months preceding the trial vaccination.
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Any known or suspected immunosuppressive illness, congenital or acquired, based on medical history and/or physical examination.
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Chronic administration (defined as more than 14 continuous days) of immunosuppressants or other immune-modifying drugs within 6 months prior to the administration of the trial vaccine. An immunosuppressant dose of glucocorticoid will be defined as a systemic dose ≥ 10 mg of prednisone per day or equivalent. The use of topical, inhaled, and nasal glucocorticoids will be permitted.
-
Administration of immunoglobulins and/or any blood products within the 3 months preceding the administration of the trial vaccine or during the trial.
-
Acute disease at the time of enrollment (defined as the presence of a moderate or severe illness with or without fever, or an oral temperature > 38.0°C, on the planned day of vaccine administration).
-
Any condition that in the opinion of the investigator would pose a health risk to the subject if enrolled or could interfere with evaluation of the vaccine or interpretation of trial results (including neurologic or psychiatric conditions deemed likely to impair the quality of safety reporting).
-
Known disturbance of coagulation.
-
Suspicion or recent history (within one year of planned vaccination) of alcohol or other substance abuse.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Research Site US108 | Raleigh | North Carolina | United States | 27609 |
| 2 | Research Site US106 | Rocky Mount | North Carolina | United States | 27804 |
| 3 | Research Site US132 | Statesville | North Carolina | United States | 28625 |
Sponsors and Collaborators
- Novavax
Investigators
- Study Director: D. Nigel Thomas, Ph.D., Novavax
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- tNIV-E-101