Phase 3 Pivotal Trial of NanoFlu™ in Older Adults

Study Overview
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Brief Summary
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A Phase 3, randomized, observer-blinded, active-controlled trial to evaluate the immunogenicity and safety of a recombinant quadrivalent nanoparticle influenza vaccine with Matrix-M1 adjuvant (NanoFlu) compared with a licensed quadrivalent inactivated influenza vaccine in adults ≥ 65 years of age. Both vaccines were formulated with the 4 influenza strains recommended for the 2019-20 Northern hemisphere influenza season. 2654 subjects were enrolled and randomized into 1 of 2 treatment groups to receive either NanoFlu or active comparator. Subjects were followed for approximately 1 year following injection; with primary immunogenicity analyses based on Day 28 sera. This trial was conducted in the United States at approximately 19 clinical sites.

Official Title
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A Phase 3, Randomized, Observer-blinded, Active-controlled Trial to Evaluate Immunogenicity & Safety of a Recombinant Quadrivalent Nanoparticle Influenza Vaccine (Quad-NIV) With Matrix-M1™ Adjuvant Against Fluzone® Quadrivalent in Clinically Stable Adults ≥ 65 Years of Age

Conditions
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Influenza, Human

Intervention / Treatment
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* Biological: NanoFlu
* Biological: Fluzone Quadrivalent


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinically-stable adult male or female, ≥ 65 years of age. Subjects may have 1 or more chronic medical diagnoses, but should be clinically stable as assessed by: Ambulatory status, living independently in the community or in a residential facility providing minimal assistance (eg, meal preparation and transport), Absence of changes in medical therapy within 1 month due to treatment failure or toxicity, Absence of medical events qualifying as serious adverse events within the prior 2 months, and Absence of known, current, and life-limiting diagnoses which render survival to completion of the protocol unlikely in the opinion of the investigator. Willing and able to give informed consent prior to trial enrollment, and Living in the community and able to attend trial visits, comply with trial requirements, and provide timely, reliable, and complete reports of adverse events. Exclusion Criteria: Participation in research involving investigational product (drug / biologic / device) within 45 days before planned date of study vaccination. Participation in any previous Novavax influenza vaccine clinical trial(s). History of a serious reaction to prior influenza vaccination, known allergy to constituents of Fluzone Quadrivalent or polysorbate 80. History of Guillain-Barré Syndrome (GBS) within 6 weeks following a previous influenza vaccine. Received any vaccine in the 4 weeks preceding the trial vaccination and any influenza vaccine within 6 months preceding the trial vaccination. Any known or suspected immunosuppressive illness, congenital or acquired, based on medical history and/or physical examination. 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. 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 1 year of planned vaccination) of alcohol or other substance abuse.

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NanoFlu<br>NanoFlu will be administered as a single dose (0.5 mL) in the arm muscle on Day 0. | Biological: NanoFlu<br>* Investigational quadrivalent seasonal influenza vaccine for the 2019-20 Northern hemisphere influenza season.<br>* Other names: Quad-NIV;|
| Active Comparator: Fluzone Quadrivalent<br>Fluzone Quadrivalent will be administered as a single dose (0.5 mL) in the arm muscle on Day 0. | Biological: Fluzone Quadrivalent<br>* Licensed quadrivalent seasonal influenza vaccine for the 2019-20 Northern hemisphere influenza season.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HAI Antibody Responses for Vaccine Homologous Influenza Strains Expressed as Ratio of Geometric Mean Fold Ratio (GMFR) | Egg-Based HAI Assay responses for all 4 vaccine homologous influenza strains (ie, 2 influenza A and 2 influenza B strains) expressed as GMFR on Day 28 | Day 28 | 
| Mean Difference in the Seroconversion Rate (SCR) HAI Antibody Responses for Vaccine Homologous Influenza Strains Expressed as a Percentage of Participants | Egg-Based HAI Assay responses for all 4 vaccine homologous influenza strains (ie, 2 influenza A and 2 influenza B strains) summarized in terms of SCR on Day 28 | Day 0 - Day 28 | 
| Number of Subjects With Solicited Local and Systemic Adverse Events (AEs) | Number of subjects with solicited local and systemic AEs over 7 days post-injection (ie, Day 0 through Day 6, inclusive). | Day 0 - Day 6 | 
| Number of Subjects With Medically Attended Adverse Events (MAAEs), Serious Adverse Events (SAEs), Significant New Medical Conditions (SNMCs) | Number of subjects with Medically Attended Adverse Events (MAAEs), Serious Adverse Events (SAEs), Significant New Medical Conditions (SNMCs) - including AESIs - through 1-year post-injection. | Day 0 - Day 364 | 
| Number of Subjects With MAAEs, SAEs, SNMCs | Number of subjects with MAEs, SAEs, and SNMCs - including AESIs. | Day 0 - Day 27 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain Expressed as Geometric Mean Titers (GMT) | Homologous influenza strains and 1 antigenically drifted strain expressed as GMT | Day 0 - Day 28 | 
| HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain Expressed as Geometric Mean Fold Ratio (GMFR) | Wild-Type HAI Assay Homologous influenza strains and 1 antigenically drifted strain expressed as GMFR. | Day 28 - 364 | 
| Subjects Who Seroconverted as Determined by HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain | Wild-Type HAI Assay Homologous Influenza Strains and at least 1 Antigenically Drifted Strain Expressed as Seroconversion Rate (SCR). | Day 28 - Day 364 | 
| Subjects Who Seroprotected as Determined by HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain Expressed as SPR | Homologous Influenza Strains and at least 1 Antigenically Drifted Strain Expressed as Seroprotection Rate (SPR). | Day 28 |