Phase 2 Dose and Formulation Confirmation of Quad-NIV in Older Adults

NCT ID: NCT03658629

Last Updated: 2022-11-04

Study Results

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

1375 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-09-24

Study Completion Date

2019-04-26

Brief Summary

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A Phase 2 trial to confirm the dose and formulation, demonstrate adjuvant effect, and evaluate the safety and tolerability of a single intramuscular injection of Quad-NIV with or without Matrix-M1 adjuvant in healthy adults ≥ 65 years of age.

A total of approximately 1375 subjects were to be randomized to seven treatment groups to receive Quad-NIV or an active comparator.

Detailed Description

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This randomized, observer-blind, active-controlled, Phase 2 trial was conducted at multiple sites. The composition of the Quad-NIV Influenza Vaccines used in this trial included recombinant H1, H3, and two B hemagglutinin proteins for the 2018-2019 Northern Hemisphere influenza virus strains.

Approximately 1375 healthy male and female subjects ≥ 65 years were randomized into 7 treatment groups (group A to group G), receiving various formulations of Quad-NIV, with or without Matrix-M1 adjuvant or one of two active comparator influenza vaccines. Within each site, randomization was stratified by history of receipt of 2017-2018 influenza vaccine. Subjects received two injections 28 days apart. On Day 0, subjects received one of the five Quad-NIV formulations or one of the two comparator influenza vaccines. On Day 28, subjects received either placebo or a licensed influenza vaccine rescue dose, depending on his or her initial randomization.

Subjects were followed for safety for approximately 6 months, with primary immunogenicity results at Day 28.

Conditions

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Influenza, Human

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Dose A

Alternating deltoid injections of Quad-NIV (60 µg HA per A strain and B strain; in-clinic mix with 50 µg of Matrix-M1) on Day 0 and Placebo on Day 28.

Group Type EXPERIMENTAL

NanoFlu (Quad-NIV)

Intervention Type BIOLOGICAL

2018-2019 Investigational Quadrivalent Seasonal Influenza Vaccine

Matrix-M Adjuvant

Intervention Type OTHER

Adjuvant

Placebo

Intervention Type OTHER

Placebo

Dose B

Alternating deltoid injections of Quad-NIV (60 µg HA per A strain and B strain; co-formulated with 50 µg of Matrix-M1) on Day 0 and Placebo on Day 28.

Group Type EXPERIMENTAL

NanoFlu (Quad-NIV)

Intervention Type BIOLOGICAL

2018-2019 Investigational Quadrivalent Seasonal Influenza Vaccine

Matrix-M Adjuvant

Intervention Type OTHER

Adjuvant

Placebo

Intervention Type OTHER

Placebo

Dose C

Alternating deltoid injections of Quad-NIV (60 µg HA per A strain and B strain; co-formulated with 75 µg of Matrix-M1) on Day 0 and Placebo on Day 28.

Group Type EXPERIMENTAL

NanoFlu (Quad-NIV)

Intervention Type BIOLOGICAL

2018-2019 Investigational Quadrivalent Seasonal Influenza Vaccine

Matrix-M Adjuvant

Intervention Type OTHER

Adjuvant

Placebo

Intervention Type OTHER

Placebo

Dose D

Alternating deltoid injections of Quad-NIV (60 µg HA per A strain and 90 µg HA per B strain; co-formulated with 50 µg of Matrix-M1) on Day 0 and Placebo on Day 28.

Group Type EXPERIMENTAL

NanoFlu (Quad-NIV)

Intervention Type BIOLOGICAL

2018-2019 Investigational Quadrivalent Seasonal Influenza Vaccine

Matrix-M Adjuvant

Intervention Type OTHER

Adjuvant

Placebo

Intervention Type OTHER

Placebo

Dose E

Alternating deltoid injections of Quad-NIV (60 µg HA per A and B strain without adjuvant) on Day 0 and Licensed 2018-2019 Influenza vaccine on Day 28.

Group Type EXPERIMENTAL

NanoFlu (Quad-NIV)

Intervention Type BIOLOGICAL

2018-2019 Investigational Quadrivalent Seasonal Influenza Vaccine

Influenza Vaccine

Intervention Type BIOLOGICAL

2018-19 Licensed Seasonal Influenza Vaccine

Dose F

Alternating deltoid injections of 2018-2019 High-Dose Trivalent Vaccine on Day 0 and Placebo on Day 28.

Group Type EXPERIMENTAL

Placebo

Intervention Type OTHER

Placebo

Fluzone HD

Intervention Type BIOLOGICAL

2018-2019 Licensed Trivalent Seasonal Influenza Vaccine

Dose G

Alternating deltoid injections of 2018-2019 Quadrivalent Vaccine on Day 0 and Placebo on Day 28.

Group Type EXPERIMENTAL

Placebo

Intervention Type OTHER

Placebo

Flublok Quadrivalent

Intervention Type BIOLOGICAL

2018-2019 Licensed Quadrivalent Seasonal Influenza Vaccine

Interventions

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NanoFlu (Quad-NIV)

2018-2019 Investigational Quadrivalent Seasonal Influenza Vaccine

Intervention Type BIOLOGICAL

Matrix-M Adjuvant

Adjuvant

Intervention Type OTHER

Placebo

Placebo

Intervention Type OTHER

Fluzone HD

2018-2019 Licensed Trivalent Seasonal Influenza Vaccine

Intervention Type BIOLOGICAL

Flublok Quadrivalent

2018-2019 Licensed Quadrivalent Seasonal Influenza Vaccine

Intervention Type BIOLOGICAL

Influenza Vaccine

2018-19 Licensed Seasonal Influenza Vaccine

Intervention Type BIOLOGICAL

Eligibility Criteria

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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:

* 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 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 first injection.
2. Participation in any previous Novavax's influenza vaccine clinical trial(s).
3. History of a serious reaction to prior influenza vaccination, known allergy to constituents of licensed comparator vaccines 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 or during the trial.
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.
Minimum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Novavax

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Development

Role: STUDY_DIRECTOR

Novavax

Locations

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US135

Hollywood, Florida, United States

Site Status

US045

Savannah, Georgia, United States

Site Status

US013

Stockbridge, Georgia, United States

Site Status

US138

Rockville, Maryland, United States

Site Status

US025

Norfolk, Nebraska, United States

Site Status

US018

Omaha, Nebraska, United States

Site Status

US078

Cary, North Carolina, United States

Site Status

US108

Raleigh, North Carolina, United States

Site Status

US137

Salisbury, North Carolina, United States

Site Status

US132

Statesville, North Carolina, United States

Site Status

US071

Wilmington, North Carolina, United States

Site Status

US063

Winston-Salem, North Carolina, United States

Site Status

US056

Moncks Corner, South Carolina, United States

Site Status

US050

Dakota Dunes, South Dakota, United States

Site Status

Countries

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United States

References

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Shinde V, Cai R, Plested J, Cho I, Fiske J, Pham X, Zhu M, Cloney-Clark S, Wang N, Zhou H, Zhou B, Patel N, Massare MJ, Fix A, Spindler M, Thomas DN, Smith G, Fries L, Glenn GM. Induction of Cross-Reactive Hemagglutination Inhibiting Antibody and Polyfunctional CD4+ T-Cell Responses by a Recombinant Matrix-M-Adjuvanted Hemagglutinin Nanoparticle Influenza Vaccine. Clin Infect Dis. 2021 Dec 6;73(11):e4278-e4287. doi: 10.1093/cid/ciaa1673.

Reference Type DERIVED
PMID: 33146720 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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Other Identifiers

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qNIV-E-201

Identifier Type: -

Identifier Source: org_study_id

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