Clinical trial NCT03300050: Safety and Immunogenicity of a Live-attenuated Universal Flu Vaccine Followed by an Inactivated Universal Flu Vaccine
Official title: A Phase 1, Randomized, Controlled, Observer-blind Study to Assess the Reactogenicity, Safety, and Immunogenicity of a Live Attenuated Universal Influenza Vaccine (cH8/1N1 LAIV) Administered as a Single Priming Dose Followed Three Months Later by a Single Booster Dose of an Inactivated Universal Influenza Vaccine (cH5/1N1 IIV) (Adjuvanted With AS03A or Unadjuvanted) in 18 Through 39 Year-old Healthy Subjects, Contrasted With a Two Dose Schedule of an Inactivated Universal Influenza Vaccine (cH8/1N1 IIV + AS03A Followed Three Months Later by cH5/1N1 IIV + AS03A)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Influenza
Vaccine
Keywords: live attenuated influenza vaccine
inactivated influenza vaccine
Lead sponsor: PATH
Sponsor class: OTHER
Collaborators: name: Icahn School of Medicine at Mount Sinai
name: Children's Hospital Medical Center, Cincinnati
name: Duke University
name: The Emmes Company, LLC
name: GlaxoSmithKline
First posted: 2017-10-03
Enrollment: 65
Sex: ALL
Minimum age (years): 18
Maximum age (years): 39
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Eligible enrolled subjects will be randomized to any of the treatment arms (LAIV-IIV, Groups 1, 2, and 3; or IIV-IIV, Groups 4 and 5) under one allocation sequence, stratified by site, to allow comparability between study groups, such as LAIV-IIV vs IIV-IIV regimens (Groups 1 vs 4). Groups 1-3 will be inpatient and receive either LAIV or placebo as nasal drops at Dose 1. Groups 4-5 ill be outpatient and receive either IIV or placebo as an injection at Dose 1.
Primary purpose: PREVENTION

Brief summary: The clinical study will evaluate safety and the immune response of a prime- boost regimen with a live attenuated influenza vaccine (LAIV) prime and an inactivated split influenza vaccine (IIV) boost with or without adjuvant.

Detailed description: This is a prospective, multi-center, randomized, controlled, observer-blind, Phase 1 trial in healthy male and female adults 18 through 39 years of age to evaluate safety and the immune response of a prime boost regimen with LAIV prime and IIV boost with or without adjuvant. Participants will be randomized 4:3:1:3:2 to one of five groups to receive a first dose of study cH8/1N1 LAIV (or placebo) or study cH8/1N1 IIV + AS03A adjuvant (or placebo) followed three months later by study cH5/1N1 IIV +/- AS03A adjuvant (or placebo).

Eligibility criteria: Inclusion Criteria:

* Able to understand planned study procedures and demonstrate comprehension of the protocol procedures and knowledge of study by passing a written examination prior to vaccination.
* In the opinion of the investigator, can and will comply with the requirements of the protocol (e.g., completion of the diary cards, return for follow-up visits).
* Written informed consent obtained from the subject prior to performance of any study specific procedure.
* Male or non-pregnant female between, and including, 18 and 39 years of age at the time of the first vaccination.
* Healthy subjects without acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality\*.
* Female subjects of non-childbearing potential may be enrolled in the study.
* Female subjects of childbearing potential must have a negative pregnancy test within 24 hours of vaccination.
* Female subjects of childbearing potential must have practiced adequate contraception for 30 days prior to first vaccination and agree to continue adequate contraception until 2 months after completion of the vaccination series (Month 5).
* Male subjects must be surgically sterile (e.g., vasectomy) or agree to practice adequate contraception from the first vaccination until 2 months after completion of the vaccination series (Month 5). Please refer to the glossary of terms for the definition of adequate contraception.

Exclusion Criteria:

* Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines.
* Any medical condition that in the judgment of the investigator would make intramuscular injection unsafe.
* Medically diagnosed deviated nasal septum or nasal obstruction.
* Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs within 6 months before the first dose.
* Administration of long-acting immune-modifying drugs (e.g., infliximab, rituximab) within 6 months before the first dose (Visit 03), or planned administration any time during the study period.
* Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting 30 days before the first dose (Visit 03) up to Month 15 (Visit 15)
* Persons who should be annually vaccinated against influenza who live with or care for persons at high risk for influenza-related complications.
* History of influenza vaccination within 6 months prior to study enrollment or unwillingness to forego seasonal influenza vaccination during the entire study period.
* History of vaccination with an investigational pandemic influenza vaccine other than an 2009 H1N1 Pandemic (H1N1pdm09) vaccine.
* Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
* Infection with human immunodeficiency virus regardless of clinical stage of immunodeficiency.
* History of current infection with hepatitis B virus or hepatitis C virus regardless of clinical presentation.
* History of or current autoimmune disease.
* Subjects diagnosed with excessive daytime sleepiness or narcolepsy; or history of narcolepsy in a subject's parent or sibling.
* History of Guillain-Barré syndrome.
* History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines (including egg proteins); a history of anaphylactic-type reaction to consumption of eggs; or a history of severe adverse reaction to a previous influenza vaccine.
* Hypersensitivity to latex.
* Administration of immunoglobulins and/or any blood products during the period starting 3 months before the first dose of study vaccines or planned administration during the study period.
* Pregnant or lactating female.
* Female planning to become pregnant or male planning to father a child or either planning to discontinue contraceptive precautions.
* Current smoker.
* During screening, have a positive test for opiates without a prescription.
* History of chronic alcohol consumption and/or drug abuse as deemed by the investigator to render the potential subject unable/unlikely to provide accurate safety reports.
* Have a history of convulsions or encephalomyelitis within 90 days prior to study vaccination.
* Have any diagnosis, current or past, of schizophrenia, bipolar disease, or other psychiatric diagnosis that may interfere with subject compliance or safety evaluations.
* Have been hospitalized for psychiatric illness, history of suicide attempt, or confinement for danger to self or others within 10 years prior to study vaccination.
* Blood donation or planned blood donation within 30 days prior to the study vaccination through 30 days after the last blood drawn for this study.
* Have signs or symptoms that could confound or confuse assessment of study vaccine reactogenicity.
* Any hematological or biochemical parameter that is out of range of normal, and is considered clinically significant by the investigator.

Primary outcomes:
measure: Number of Participants With Solicited Local Reactions Within 7 Days Following Each Vaccination
timeFrame: 7 days after each vaccination (Days 1-8 and Days 85-92)
measure: Number of Participants With Solicited General Reactions Within 7 Days Following Each Vaccination
timeFrame: 7 days after each vaccination (Days 1-8 and Days 85-92)
measure: Number of Participants With Unsolicited Adverse Events Within 28 Days Following Any Vaccination
timeFrame: 28 days after each vaccination (Days 1 to 28 and Days 85 to 113)
measure: Number of Participants With Grade 2 or Higher Hematological and Biochemical Laboratory Abnormalities From Day 8 to Day 113
timeFrame: Days 8, 29, 85, 92, and 113
measure: Number of Participants With a Medically Attended Event (MAE), Laboratory-Confirmed Influenza-like Illness (LC-ILI), Potential Immune-mediated Disease (pIMD), or Serious Adverse Event (SAE) up to Day 113
timeFrame: Through Day 113 (28 days post-dose 2)
Secondary outcomes:
measure: Number of Participants With Any Grade 2 or Higher Hematological and Biochemical Laboratory Abnormalities From Month 9 to Month 15
timeFrame: Month 9 (6 months post-dose 2) and Month 15 (12 months post-dose 2)
measure: Number of Participants With a Medically Attended Event (MAE), Laboratory-Confirmed Influenza-like Illness (LC-ILI), Potential Immune-mediated Disease (pIMD), or Serious Adverse Event (SAE) up to End of Study
timeFrame: From first dose to end of study, 588 days (21 months; 18 months post-dose 2)
measure: Number of Participants in Groups 1, 2, and 3 With Detectable Influenza A Virus in Nasal and Oropharyngeal Swabs on Days 1 to 5
timeFrame: Days 1 to 5
measure: Number of Participants in Groups 1, 2, and 3 With Viable Vaccine Virus in Cell Culture Through 5 Days Post-vaccination
timeFrame: Days 1 to 5
measure: Percentage of Participants With Serum Anti-H1 Hemagglutinin Stalk Immunoglobulin G Antibody Seropositivity
timeFrame: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), Month 9 (6 months post-dose 2), and Month 15 (12 months post-dose 2)
measure: Geometric Mean Titer of Serum Anti-H1 Hemagglutinin Stalk IgG Antibodies
timeFrame: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), Month 9 (6 months post-dose 2), and Month 15 (12 months post-dose 2)
measure: Percentage of Participants With a ≥ 4-fold Increase From Baseline in Serum Anti-H1 Hemagglutinin Stalk IgG Antibodies
timeFrame: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), Month 9 (6 months post-dose 2), and Month 15 (12 months post-dose 2)
measure: Percentage of Participants With a ≥ 10-fold Increase From Baseline in Serum Anti-H1 Hemagglutinin Stalk IgG Antibodies
timeFrame: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), Month 9 (6 months post-dose 2), and Month 15 (12 months post-dose 2)
measure: Mean Geometric Increase From Baseline in Serum Anti-H1 Hemagglutinin Stalk IgG Antibodies
timeFrame: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), Month 9 (6 months post-dose 2), and Month 15 (12 months post-dose 2)
measure: Percentage of Participants With Serum Anti-H1 Hemagglutinin Stalk Immunoglobulin A Antibody Seropositivity
timeFrame: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
measure: Geometric Mean Titer of Serum Anti-H1 Hemagglutinin Stalk IgA Antibodies
timeFrame: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
measure: Percentage of Participants With a ≥ 4-fold Increase From Baseline in Serum Anti-H1 Hemagglutinin Stalk IgA Antibodies
timeFrame: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
measure: Percentage of Participants With a ≥ 10-fold Increase From Baseline in Serum Anti-H1 Hemagglutinin Stalk IgA Antibodies
timeFrame: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
measure: Mean Geometric Increase From Baseline in Serum Anti-H1 Hemagglutinin Stalk IgA Antibodies
timeFrame: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
measure: Percentage of Participants With Serum Anti-H1 Hemagglutinin Stalk Neutralizing Antibody Seropositivity
timeFrame: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
measure: Geometric Mean Titer of Serum Anti-H1 Hemagglutinin Stalk Neutralizing Antibodies
timeFrame: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
measure: Percentage of Participants With a ≥ 4-fold Increase From Baseline in Serum Anti-H1 Hemagglutinin Stalk Neutralizing Antibodies
timeFrame: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
measure: Percentage of Participants With a ≥ 10-fold Increase From Baseline in Serum Anti-H1 Hemagglutinin Stalk Neutralizing Antibodies
timeFrame: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
measure: Mean Geometric Increase From Baseline in Serum Anti-H1 Hemagglutinin Stalk Neutralizing Antibodies
timeFrame: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
measure: Serum Antibody-dependent Cell-mediated Cytotoxicity (ADCC) to the H1 Hemagglutinin Stalk
timeFrame: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
measure: Fold-Increase From Baseline in Serum ADCC to the H1 Hemagglutinin Stalk
timeFrame: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
measure: Percentage of Participants With a ≥ 4-fold Increase From Baseline in Serum ADCC to the H1 Hemagglutinin Stalk
timeFrame: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
measure: Percentage of Participants With a ≥ 10-fold Increase From Baseline in Serum ADCC to the H1 Hemagglutinin Stalk
timeFrame: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
measure: Percentage of Participants With Anti-H1 Hemagglutinin Stalk Salivary IgG Antibody Seropositivity
timeFrame: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
measure: Geometric Mean Titer of Anti-H1 Hemagglutinin Stalk Salivary IgG Antibodies
timeFrame: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
measure: Percentage of Participants With a ≥ 4-fold Increase From Baseline in Anti-H1 Hemagglutinin Stalk Salivary IgG
timeFrame: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
measure: Percentage of Participants With a ≥ 10-fold Increase From Baseline in Anti-H1 Hemagglutinin Stalk Salivary IgG
timeFrame: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
measure: Mean Geometric Increase of Anti-H1 Hemagglutinin Stalk Salivary IgG Antibodies
timeFrame: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
measure: Percentage of Participants With Anti-H1 Hemagglutinin Stalk Secretory IgA Antibody Seropositivity in Saliva
timeFrame: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
measure: Geometric Mean Titer of Anti-H1 Hemagglutinin Stalk Secretory IgA Antibodies in Saliva
timeFrame: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
measure: Percentage of Participants With a ≥ 4-fold Increase From Baseline in Anti-H1 Hemagglutinin Stalk Secretory IgA Antibodies in Saliva
timeFrame: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
measure: Percentage of Participants With a ≥ 10-fold Increase From Baseline in Anti-H1 Hemagglutinin Stalk Secretory IgA Antibodies in Saliva
timeFrame: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
measure: Mean Geometric Increase From Baseline in Anti-H1 Hemagglutinin Stalk Secretory IgA in Saliva
timeFrame: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
measure: Percentage of Participants With Anti-H1 Hemagglutinin Stalk Total IgA Antibody Seropositivity in Saliva
timeFrame: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
measure: Geometric Mean Titer of Anti-H1 Hemagglutinin Stalk Total IgA Antibodies in Saliva
timeFrame: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
measure: Percentage of Participants With a ≥ 4-fold Increase From Baseline in Anti-H1 Hemagglutinin Stalk Total IgA Antibodies in Saliva
timeFrame: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
measure: Percentage of Participants With a ≥ 10-fold Increase From Baseline in Anti-H1 Hemagglutinin Stalk Total IgA Antibodies in Saliva
timeFrame: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
measure: Mean Geometric Increase From Baseline in Anti-H1 Hemagglutinin Stalk Total IgA Antibodies in Saliva
timeFrame: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
measure: Percentage of Participants With Serum Anti-H2 Full-length Hemagglutinin IgG Antibody Seropositivity
timeFrame: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
measure: Geometric Mean Titer of Serum Anti-H2 Full-length Hemagglutinin IgG Antibodies
timeFrame: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
measure: Percentage of Participants With a ≥ 4-fold Increase From Baseline in Serum Anti-H2 Full-length Hemagglutinin IgG Antibodies
timeFrame: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
measure: Percentage of Participants With a ≥ 10-fold Increase From Baseline in Serum Anti-H2 Full-length Hemagglutinin IgG Antibodies
timeFrame: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
measure: Mean Geometric Increase of Serum Anti-H2 Full-length Hemagglutinin IgG Antibodies
timeFrame: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
measure: Percentage of Participants With Serum Anti-H9 Full-length Hemagglutinin IgG Antibody Seropositivity
timeFrame: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
measure: Geometric Mean Titer of Serum Anti-H9 Full-length Hemagglutinin IgG Antibodies
timeFrame: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
measure: Percentage of Participants With a ≥ 4-fold Increase From Baseline in Serum Anti-H9 Full-length Hemagglutinin IgG Antibodies
timeFrame: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
measure: Percentage of Participants With a ≥ 10-fold Increase From Baseline in Serum Anti-H9 Full-length Hemagglutinin IgG Antibodies
timeFrame: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
measure: Mean Geometric Increase of Serum Anti-H9 Full-length Hemagglutinin IgG Antibodies
timeFrame: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
measure: Percentage of Participants With Serum Anti-H18 Full-length Hemagglutinin IgG Antibody Seropositivity
timeFrame: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
measure: Geometric Mean Titer of Serum Anti-H18 Full-length Hemagglutinin IgG Antibodies
timeFrame: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
measure: Percentage of Participants With a ≥ 4-fold Increase From Baseline in Serum Anti-H18 Full-length Hemagglutinin IgG Antibodies
timeFrame: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
measure: Percentage of Participants With a ≥ 10-fold Increase From Baseline in Serum Anti-H18 Full-length Hemagglutinin IgG Antibodies
timeFrame: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
measure: Mean Geometric Increase of Serum Anti-H18 Full-length Hemagglutinin IgG Antibodies
timeFrame: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
measure: Percentage of Participants With Serum Anti-Human H1N1 Virus Neutralizing Antibody Seropositivity
timeFrame: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
measure: Geometric Mean Titer of Serum Anti-Human H1N1 Virus Neutralizing Antibodies
timeFrame: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
measure: Percentage of Participants With a ≥ 4-fold Increase in Serum Anti-Human H1N1 Virus Neutralizing Antibodies
timeFrame: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
measure: Percentage of Participants With a ≥ 10-fold Increase From Baseline in Serum Anti-Human H1N1 Virus Neutralizing Antibodies
timeFrame: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
measure: Mean Geometric Increase of Serum Anti-Human H1N1 Virus Neutralizing Antibodies
timeFrame: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
measure: Percentage of Participants With Serum Anti-Avian-Swine H1N1 Virus Neutralizing Antibody Seropositivity
timeFrame: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
measure: Geometric Mean Titer of Serum Anti-Avian-Swine H1N1 Virus Neutralizing Antibodies
timeFrame: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
measure: Percentage of Participants With a ≥ 4-fold Increase in Serum Anti-Avian-Swine H1N1 Virus Neutralizing Antibodies
timeFrame: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
measure: Percentage of Participants With a ≥ 10-fold Increase in Serum Anti-Avian-Swine H1N1 Virus Neutralizing Antibodies
timeFrame: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
measure: Mean Geometric Increase From Baseline in Serum Anti-Avian-Swine H1N1 Virus Neutralizing Antibodies
timeFrame: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
measure: Percentage of Participants With Serum Anti-H5N8 Virus Neutralizing Antibody Seropositivity
timeFrame: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
measure: Geometric Mean Titer of Serum Anti-H5N8 Virus Neutralizing Antibodies
timeFrame: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
measure: Percentage of Participants With a ≥ 4-fold Increase in Serum Anti-H5N8 Virus Neutralizing Antibodies
timeFrame: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
measure: Percentage of Participants With a ≥ 10-fold Increase in Serum Anti-H5N8 Virus Neutralizing Antibodies
timeFrame: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
measure: Mean Geometric Increase From Baseline in Serum Anti-H5N8 Virus Neutralizing Antibodies
timeFrame: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
Study officials:
affiliation: Children's Hospital Medical Center, Cincinnati
name: David Bernstein, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Duke University
name: Jeffrey Guptill, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Nachbagauer R, Feser J, Naficy A, Bernstein DI, Guptill J, Walter EB, Berlanda-Scorza F, Stadlbauer D, Wilson PC, Aydillo T, Behzadi MA, Bhavsar D, Bliss C, Capuano C, Carreno JM, Chromikova V, Claeys C, Coughlan L, Freyn AW, Gast C, Javier A, Jiang K, Mariottini C, McMahon M, McNeal M, Solorzano A, Strohmeier S, Sun W, Van der Wielen M, Innis BL, Garcia-Sastre A, Palese P, Krammer F. A chimeric hemagglutinin-based universal influenza virus vaccine approach induces broad and long-lasting immunity in a randomized, placebo-controlled phase I trial. Nat Med. 2021 Jan;27(1):106-114. doi: 10.1038/s41591-020-1118-7. Epub 2020 Dec 7.
citation: Bernstein DI, Guptill J, Naficy A, Nachbagauer R, Berlanda-Scorza F, Feser J, Wilson PC, Solorzano A, Van der Wielen M, Walter EB, Albrecht RA, Buschle KN, Chen YQ, Claeys C, Dickey M, Dugan HL, Ermler ME, Freeman D, Gao M, Gast C, Guthmiller JJ, Hai R, Henry C, Lan LY, McNeal M, Palm AE, Shaw DG, Stamper CT, Sun W, Sutton V, Tepora ME, Wahid R, Wenzel H, Wohlbold TJ, Innis BL, Garcia-Sastre A, Palese P, Krammer F. Immunogenicity of chimeric haemagglutinin-based, universal influenza virus vaccine candidates: interim results of a randomised, placebo-controlled, phase 1 clinical trial. Lancet Infect Dis. 2020 Jan;20(1):80-91. doi: 10.1016/S1473-3099(19)30393-7. Epub 2019 Oct 17.