Clinical trial NCT03658629: Phase 2 Dose and Formulation Confirmation of Quad-NIV in Older Adults
Official title: Phase 2 Clinical Trial to Confirm the Dose and Formulation of a Recombinant Quadrivalent Nanoparticle Influenza Vaccine (Quad-NIV) With or Without Matrix-M1™ Adjuvant in Healthy Adults ≥ 65 Years of Age
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Influenza, Human
Lead sponsor: Novavax
Sponsor class: INDUSTRY
First posted: 2018-09-05
Enrollment: 1375
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 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: 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.

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:

   * 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.

Primary outcomes:
measure: Number of Subjects With Adverse Events (AEs)
timeFrame: Day 0 - Day 182
measure: Hemagglutination Inhibition (HAI) Titers Specific for Vaccine Homologous A and B Influenza Strains Expressed as Geometric Man Titer (GMT)
timeFrame: Day 0 - Day 28
measure: HAI Titers Specific for Antigenically-drifted Influenza Strains Expressed as GMT
timeFrame: Day 0 - Day 28
Secondary outcomes:
measure: HAI Titers Specific for Vaccine-homologous A and B Influenza Strains Expressed as GMT
timeFrame: Day 0 - Day 182
measure: HAI Titers Specific for Vaccine-homologous A and B Influenza Strains Expressed as Geometric Mean Fold Ratio (GMFR)
timeFrame: Day 28 - Day 182
measure: Number of Participants Who Seroconverted as Determined by HAI Titers Specific for Vaccine-homologous A and B Influenza Strains
timeFrame: Day 28 - Day 182
measure: Number of Participants Who Had Seroprotection as Determined by HAI Titers Specific for Vaccine-homologous A and B Influenza Strains
timeFrame: Day 28 - Day 182
measure: HAI Titers Specific for Antigenically-drifted Influenza Strains Expressed as GMT
timeFrame: Day 0 - Day 182
measure: HAI Titer Responses Specific for Antigenically-drifted Influenza Strains Expressed as GMFR
timeFrame: Day 28 - Day 182
measure: Number of Participants Who Seroconverted as Determined by HAI Titers Specific for Antigenically-drifted Influenza Strains
timeFrame: Day 28 - Day 182
measure: Number of Participants Who Had Seroprotection as Determined by HAI Titers of Antigenically-drifted Influenza Strains
timeFrame: Day 28 - Day 182
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: 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: Cary
country: United States
facility: US078
state: North Carolina
city: Raleigh
country: United States
facility: US108
state: North Carolina
city: Salisbury
country: United States
facility: US137
state: North Carolina
city: Statesville
country: United States
facility: US132
state: North Carolina
city: Wilmington
country: United States
facility: US071
state: North Carolina
city: Winston-Salem
country: United States
facility: US063
state: North Carolina
city: Moncks Corner
country: United States
facility: US056
state: South Carolina
city: Dakota Dunes
country: United States
facility: US050
state: South Dakota
Study officials:
affiliation: Novavax
name: Clinical Development
role: STUDY_DIRECTOR
References:
citation: 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.