Phase 3 Pivotal Trial of NanoFlu™ in Older Adults

Phase 3

Completed

• Conditions: Influenza, Human
• Interventions: Biological: NanoFlu; Biological: Fluzone Quadrivalent

• Registration Number: NCT04120194
• Lead Sponsor: Novavax

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-10-07
• Study First Submitted QC: 2019-10-07
• Study First Posted: 2019-10-09
• Study Start: 2019-10-14
• Primary Completion: 2020-10-29
• Study Completion: 2020-12-13
• Results First Submitted: 2022-08-22
• Status Verified: 2023-04
• Results First Submitted QC: 2023-04-11
• Last Update Submitted: 2023-04-11
• Results First Posted: 2023-05-06
• Last Update Posted: 2023-05-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 2654

Inclusion Criteria

1. 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.

2. Willing and able to give informed consent prior to trial enrollment, and

3. Living in the community and able to attend trial visits, comply with trial requirements, and provide timely, reliable, and complete reports of adverse events.

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Exclusion Criteria

1. Participation in research involving investigational product (drug / biologic / device) within 45 days before planned date of study vaccination.
2. Participation in any previous Novavax influenza vaccine clinical trial(s).
3. History of a serious reaction to prior influenza vaccination, known allergy to constituents of Fluzone Quadrivalent or polysorbate 80.
4. History of Guillain-Barré Syndrome (GBS) within 6 weeks following a previous influenza vaccine.
5. Received any vaccine in the 4 weeks preceding the trial vaccination and any influenza vaccine within 6 months preceding the trial vaccination.
6. Any known or suspected immunosuppressive illness, congenital or acquired, based on medical history and/or physical examination.
7. 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.
8. Administration of immunoglobulins and/or any blood products within the 3 months preceding the administration of the trial vaccine.
9. 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).
10. 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).
11. Known disturbance of coagulation.
12. Suspicion or recent history (within 1 year of planned vaccination) of alcohol or other substance abuse.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
NanoFlu	NanoFlu	NanoFlu will be administered as a single dose (0.5 mL) in the arm muscle on Day 0.
Fluzone Quadrivalent	Fluzone Quadrivalent	Fluzone Quadrivalent will be administered as a single dose (0.5 mL) in the arm muscle on Day 0.

Primary Outcome Measures

Name	Time	Method
Mean Difference in the Seroconversion Rate (SCR) HAI Antibody Responses for Vaccine Homologous Influenza Strains Expressed as a Percentage of Participants	Day 0 - Day 28	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
HAI Antibody Responses for Vaccine Homologous Influenza Strains Expressed as Ratio of Geometric Mean Fold Ratio (GMFR)	Day 28	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
Number of Subjects With Solicited Local and Systemic Adverse Events (AEs)	Day 0 - Day 6	Number of subjects with solicited local and systemic AEs over 7 days post-injection (ie, Day 0 through Day 6, inclusive).
Number of Subjects With Medically Attended Adverse Events (MAAEs), Serious Adverse Events (SAEs), Significant New Medical Conditions (SNMCs)	Day 0 - Day 364	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.
Number of Subjects With MAAEs, SAEs, SNMCs	Day 0 - Day 27	Number of subjects with MAEs, SAEs, and SNMCs - including AESIs.

Secondary Outcome Measures

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

Trial Locations

Locations (19)

US045; 🇺🇸 Savannah, Georgia, United States

US135; 🇺🇸 Hollywood, Florida, United States

US025; 🇺🇸 Norfolk, Nebraska, United States

US050; 🇺🇸 Dakota Dunes, South Dakota, United States

US044; 🇺🇸 Warwick, Rhode Island, United States

US013; 🇺🇸 Stockbridge, Georgia, United States

US012; 🇺🇸 Meridian, Idaho, United States

US003; 🇺🇸 Lenexa, Kansas, United States

US138; 🇺🇸 Rockville, Maryland, United States

US056; 🇺🇸 Binghamton, New York, United States

US017; 🇺🇸 Endwell, New York, United States

US032; 🇺🇸 Nampa, Idaho, United States

US018; 🇺🇸 Omaha, Nebraska, United States

US030; 🇺🇸 Cleveland, Ohio, United States

US053; 🇺🇸 Oklahoma City, Oklahoma, United States

US029; 🇺🇸 Nashville, Tennessee, United States

US004; 🇺🇸 San Antonio, Texas, United States

US073; 🇺🇸 Tomball, Texas, United States

US079; 🇺🇸 Mount Pleasant, South Carolina, United States