Clinical trial NCT04120194: Phase 3 Pivotal Trial of NanoFlu™ in Older Adults
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Influenza, Human
Lead sponsor: Novavax
Sponsor class: INDUSTRY
First posted: 2019-10-09
Enrollment: 2654
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility criteria: 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.

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.

Primary outcomes:
measure: HAI Antibody Responses for Vaccine Homologous Influenza Strains Expressed as Ratio of Geometric Mean Fold Ratio (GMFR)
timeFrame: Day 28
measure: Mean Difference in the Seroconversion Rate (SCR) HAI Antibody Responses for Vaccine Homologous Influenza Strains Expressed as a Percentage of Participants
timeFrame: Day 0 - Day 28
measure: Number of Subjects With Solicited Local and Systemic Adverse Events (AEs)
timeFrame: Day 0 - Day 6
measure: Number of Subjects With Medically Attended Adverse Events (MAAEs), Serious Adverse Events (SAEs), Significant New Medical Conditions (SNMCs)
timeFrame: Day 0 - Day 364
measure: Number of Subjects With MAAEs, SAEs, SNMCs
timeFrame: Day 0 - Day 27
Secondary outcomes:
measure: HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain Expressed as Geometric Mean Titers (GMT)
timeFrame: Day 0 - Day 28
measure: HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain Expressed as Geometric Mean Fold Ratio (GMFR)
timeFrame: Day 28 - 364
measure: Subjects Who Seroconverted as Determined by HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain
timeFrame: Day 28 - Day 364
measure: Subjects Who Seroprotected as Determined by HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain Expressed as SPR
timeFrame: Day 28
Other outcomes:
Locations:
city: Hollywood
country: United States
facility: US135
state: Florida
city: Savannah
country: United States
facility: US045
state: Georgia
city: Stockbridge
country: United States
facility: US013
state: Georgia
city: Meridian
country: United States
facility: US012
state: Idaho
city: Nampa
country: United States
facility: US032
state: Idaho
city: Lenexa
country: United States
facility: US003
state: Kansas
city: Rockville
country: United States
facility: US138
state: Maryland
city: Norfolk
country: United States
facility: US025
state: Nebraska
city: Omaha
country: United States
facility: US018
state: Nebraska
city: Binghamton
country: United States
facility: US056
state: New York
city: Endwell
country: United States
facility: US017
state: New York
city: Cleveland
country: United States
facility: US030
state: Ohio
city: Oklahoma City
country: United States
facility: US053
state: Oklahoma
city: Warwick
country: United States
facility: US044
state: Rhode Island
city: Mount Pleasant
country: United States
facility: US079
state: South Carolina
city: Dakota Dunes
country: United States
facility: US050
state: South Dakota
city: Nashville
country: United States
facility: US029
state: Tennessee
city: San Antonio
country: United States
facility: US004
state: Texas
city: Tomball
country: United States
facility: US073
state: Texas
Study officials:
affiliation: Novavax, Inc.
name: Clinical Development
role: STUDY_DIRECTOR
References:
citation: Shinde V, Cho I, Plested JS, Agrawal S, Fiske J, Cai R, Zhou H, Pham X, Zhu M, Cloney-Clark S, Wang N, Zhou B, Lewis M, Price-Abbott P, Patel N, Massare MJ, Smith G, Keech C, Fries L, Glenn GM. Comparison of the safety and immunogenicity of a novel Matrix-M-adjuvanted nanoparticle influenza vaccine with a quadrivalent seasonal influenza vaccine in older adults: a phase 3 randomised controlled trial. Lancet Infect Dis. 2022 Jan;22(1):73-84. doi: 10.1016/S1473-3099(21)00192-4. Epub 2021 Sep 23.