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
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Influenza
- Sponsor
- Novavax
- Enrollment
- 330
- Locations
- 3
- Primary Endpoint
- 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.
- Status
- Completed
- Last Updated
- 3 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Healthy older adults, male or female,
- •Willing and able to give informed consent prior to trial enrollment, and
- •Able to attend trial visits, comply with trial requirements, and provide reliable and complete reports of adverse events.
Exclusion Criteria
- •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).
- •Participation in research involving investigational product (drug / biologic / device) within 45 days before planned date of first injection.
- •History of a serious reaction to prior influenza vaccination, or known allergy to constituents of influenza vaccines - including egg proteins - or polysorbate
- •History of Guillain-Barré Syndrome (GBS) within 6 weeks following a previous influenza vaccine.
- •Receipt of any vaccine in the 4 weeks preceding the trial vaccination and any influenza vaccine within 6 months preceding the trial vaccination.
- •Any known or suspected immunosuppressive illness, congenital or acquired, based on medical history and/or physical examination.
Outcomes
Primary Outcomes
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.
Time Frame: Day 0 - Day 21 post dosing
The immunogenicity of Tri-NIV at 2 different doses, and the licensed comparator Fluzone HD (Sanofi Pasteur), in healthy older adults ≥ 60 years of age, based on hemagglutination inhibition (HAI) responses to vaccine-homologous influenza A and B strains, as recommended for the 2017 - 18 Northern hemisphere vaccine, at Day 21 post-dosing expressed as GMR.
Number of Participants With All Adverse Events (AEs), Medically Attended Adverse Events (MAAEs), Serious Adverse Events (SAEs), and Significant New Medical Conditions (SNMCs).
Time Frame: Day 0 - Day 21 post dosing
Number of participants that reported all adverse event (AE) profile (including adverse changes in clinical laboratory parameters) ; medically-attended adverse event (MAE), serious adverse event (SAE), and significant new medical condition (SNMC) post dosing.
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.
Time Frame: Day 0 - Day 21 post dosing
The immunogenicity of Tri-NIV at 2 different doses, and the licensed comparator Fluzone HD (Sanofi Pasteur), in healthy older adults ≥ 60 years of age, based on hemagglutination inhibition (HAI) responses to vaccine-homologous influenza A and B strains, as recommended for the 2017 - 18 Northern hemisphere vaccine, at Day 21 post-dosing expressed as GMTs.
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.
Time Frame: Day 0 - Day 21 post dosing
The immunogenicity of Tri-NIV at 2 different doses, and the licensed comparator Fluzone HD (Sanofi Pasteur), in healthy older adults ≥ 60 years of age, based on hemagglutination inhibition (HAI) responses to vaccine-homologous influenza A and B strains, as recommended for the 2017 - 18 Northern hemisphere vaccine, at Day 21 post-dosing expressed as SCRs.
Number of Participants With Solicited Local and Systemic AEs
Time Frame: Day 0 - Day 6 post-dosing
Number of participants with solicited local and systemic adverse events over the 7 days post-injection
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.
Time Frame: Day 0 - Day 21 post dosing
The immunogenicity of Tri-NIV at 2 different doses, and the licensed comparator Fluzone HD (Sanofi Pasteur), in healthy older adults ≥ 60 years of age, based on hemagglutination inhibition (HAI) responses to vaccine-homologous influenza A and B strains, as recommended for the 2017 - 18 Northern hemisphere vaccine, at Day 21 post-dosing expressed as SPRs. Seroprotection rate (SPR) - defined as the number of subjects with an HAI titer ≥ 1:40.
Secondary Outcomes
- 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.(Day 0 - Day 21)
- 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(Day 0 - Day 21)
- 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(Day 0 - Day 21)
- 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.(Day 0 - Day 21)
- 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(Day 0 - Day 21)
- 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(Day 0 - Day 21)
- 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.(Day 0 - Day 21 post dosing)