Clinical trial NCT03293498: Evaluation of the Safety and Immunogenicity of a Recombinant Trivalent Nanoparticle Influenza Vaccine With Matrix M-1 Adjuvant (NanoFlu)
Official title: A Phase 1/2, Randomized, Observer-Blinded, Active-Controlled Trials to Evaluate the Safety and Immunogenicity of a Recombinant Trivalent Nanoparticle Influenza Vaccine With Matrix-M1 Adjuvant (NanoFlu) in Healthy Older Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Influenza
Lead sponsor: Novavax
Sponsor class: INDUSTRY
First posted: 2017-09-26
Enrollment: 330
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This was a Phase 1/2, randomized, observer-blinded, active-controlled trial to assess the Safety and Tolerability of a Recombinant Trivalent Nanoparticle Influenza Vaccine (Tri-NIV) with Matrix M1™ Adjuvant in Healthy Older Adults ≥ 60 Years of Age

Detailed description: Study tNIV-E-101 a randomized, observer-blinded, active-controlled trial designed to evaluate the safety and immunogenicity of Novavax's insect cell-derived, egg-free, influenza vaccine (Tri-NIV) based on recombinant HA nanoparticle antigens, representing the 3 major influenza types/subtypes recommended for inclusion in the 2017 - 2018 seasonal influenza vaccine by the World Health Organization (WHO) and the Center for Biologics Evaluation and Research (CBER) Approximately 330 eligible subjects were enrolled and randomized into 1 of 3 treatment groups Each group consisted of approximately 110 subjects total, stratified by age, gender, and history of receipt of the 2016 - 17 influenza vaccine. On Day 0, subjects in Groups A and B were administered an IM injection of NanoFlu at one of two dose levels; subjects in Group C received the preconfigured comparator (Fluzone HD) at the manufacturer's recommended dose and volume. On Day 21, all Group A and B subjects were administered a rescue injection with a licensed seasonal influenza vaccine. In contrast, all Group C subjects were administered an injection with a sterile saline placebo to maintain the trial blind. Trial follow-up for each subject spanned approximately 1 year from Day 0.

Eligibility criteria: Inclusion Criteria:

1. Healthy older adults, male or female,
2. Willing and able to give informed consent prior to trial enrollment, and
3. Able to attend trial visits, comply with trial requirements, and provide reliable and complete reports of adverse events.

Exclusion Criteria:

1. Any ongoing, symptomatic acute or chronic illness requiring medical or surgical care.

   * Asymptomatic chronic conditions or findings (eg, mild hypertension, dyslipidemia) that are not associated with evidence of end-organ damage are not exclusionary provided that they are being appropriately managed and are clinically stable (ie, unlikely to result in symptomatic illness within the time-course of this trial) in the opinion of the investigator.
   * Acute or chronic illnesses or conditions which may be reasonably predicted to become symptomatic if treatment were withdrawn or interrupted are exclusionary, even if stable.
   * Acute or chronic illnesses reasonably expected to be associated with increased risks in the event of influenza infection (eg, cardio-pulmonary diseases, diabetes mellitus, renal or hepatic dysfunction, hemoglobinopathies) are exclusionary, even if stable.
   * Note that illnesses or conditions may be exclusionary, even if otherwise stable, due to therapies used to treat them (see exclusion criteria 2, 5, 8, 9).
2. Participation in research involving investigational product (drug / biologic / device) within 45 days before planned date of first injection.
3. History of a serious reaction to prior influenza vaccination, or known allergy to constituents of influenza vaccines - including egg proteins - or polysorbate 80.
4. History of Guillain-Barré Syndrome (GBS) within 6 weeks following a previous influenza vaccine.
5. Receipt of 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 one year of planned vaccination) of alcohol or other substance abuse.

Primary outcomes:
measure: Number of Participants With All Adverse Events (AEs), Medically Attended Adverse Events (MAAEs), Serious Adverse Events (SAEs), and Significant New Medical Conditions (SNMCs).
timeFrame: Day 0 - Day 21 post dosing
measure: Number of Participants With Solicited Local and Systemic AEs
timeFrame: Day 0 - Day 6 post-dosing
measure: Geometric Mean Titers (GMT) Specific for the Hemagglutinin (HA) Receptor Binding Domains of Each of the Virus Strains Included in the NanoFlu as Measured by the Hemagglutination Inhibition (HAI) Assay.
timeFrame: Day 0 - Day 21 post dosing
measure: Geometric Mean Ratio (GMR) Specific for the HA Receptor Binding Domains of Each of the Virus Strains Included in the NanoFlu as Measured by the HAI Assay.
timeFrame: Day 0 - Day 21 post dosing
measure: Seroconversion Rate (SCR) Specific for the HA Receptor Binding Domains of Each of the Virus Strains Included in the NanoFlu as Measured by the HAI Assay.
timeFrame: Day 0 - Day 21 post dosing
measure: Number of Participants With Seroprotection Specific for the HA Receptor Binding Domains of Each of the Virus Strains Included in the NanoFlu as Measured by the HAI Assay.
timeFrame: Day 0 - Day 21 post dosing
Secondary outcomes:
measure: Geometric Mean Titers (GMT) Specific for the HA Receptor Binding Domains of at Least 2 Historic A Virus Strains (One H1N1 and One H3N2) as Measured by the HAI Assay
timeFrame: Day 0 - Day 21
measure: Geometric Mean Ratio (GMR) Specific for the HA Receptor Binding Domains of at Least 2 Historic A Virus Strains (One H1N1 and One H3N2) as Measured by the HAI Assay
timeFrame: Day 0 - Day 21
measure: Seroconversion Rate (SCR) Specific for the HA Receptor Binding Domains of at Least 2 Historic A Virus Strains (One H1N1 and One H3N2) as Measured by the HAI Assay
timeFrame: Day 0 - Day 21
measure: Number of Participants With Seroprotection Specific for the HA Receptor Binding Domains of at Least 2 Historic A Virus Strains (One H1N1 and One H3N2) as Measured by the HAI Assay
timeFrame: Day 0 - Day 21
measure: Geometric Mean Titers (GMT) for Neutralizing Antibody Titers Specific for the Virus Strains Included in NanoFlu and the Fluzone HD Comparator, as Well as Selected Historical A Strains, as Measured by a Microneutralization Assay.
timeFrame: Day 0 - Day 21 post dosing
measure: Geometric Mean Ratio (GMR) for Neutralizing Antibody Titers Specific for the Virus Strains Included in NanoFlu and the Fluzone HD Comparator, as Well as Selected Historical A Strains, as Measured by a Microneutralization Assay.
timeFrame: Day 0 - Day 21
measure: Seroconversion Rate (SCR) for Neutralizing Antibody Titers Specific for the Virus Strains Included in NanoFlu and the Fluzone HD Comparator, as Well as Selected Historical A Strains, as Measured by a Microneutralization Assay.
timeFrame: Day 0 - Day 21
Other outcomes:
Locations:
city: Raleigh
country: United States
facility: Research Site US108
state: North Carolina
city: Rocky Mount
country: United States
facility: Research Site US106
state: North Carolina
city: Statesville
country: United States
facility: Research Site US132
state: North Carolina
Study officials:
affiliation: Novavax
name: Clinical Development
role: STUDY_DIRECTOR
References: