A Phase II Study to Evaluate and Compare the Immunogenicity of Monovalent Inactivated Influenza A/H7N9 Virus Vaccine Administered With and Without AS03 Adjuvant and Monovalent Inactivated Influenza A/H3N2v Virus Vaccine Administered Without Adjuvant in Healthy Adults Through Standard and Systems Biology Analyses
Overview
- Phase
- Phase 2
- Intervention
- Influenza Virus Vaccine, Monovalent A/H3N2v A/Minnesota/11/2010 NYMC X-203
- Conditions
- Avian Influenza
- Sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- Number of Differentially Expressed Genes Based on RNA Expression in Human Immune Cells (A/H7N9 Vaccine, With and Without Adjuvant)
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
This is a single center, randomized, partially-blinded, Phase II, small, targeted, prospective study in approximately 30 healthy male and non-pregnant female subjects aged 18 to 49 years old, inclusive, designed to evaluate and compare the immunogenicity between an intramuscular monovalent inactivated influenza A/H7N9 virus vaccine given with and without AS03 adjuvant, and an intramuscular unadjuvanted monovalent inactivated influenza A/H3N2v virus vaccine. The primary objectives are (1) assessing the serum anti-HA hemagglutination-inhibition (HAI) response to influenza A/H7N9 antigen (with and without adjuvant) at Day 57 (approximately one month after the second study vaccination with A/H7N9 vaccine with or without AS03) and influenza A/H3N2v antigen at Day 29 (approximately one month after the study vaccination with A/H3N2v), and (2) identifying differentially expressed genes in human immune cells on Days 2, 4, and 29 (following the first study vaccination with A/H7N9 vaccine with or without AS03) and on Days 30, 32, and 36 (following the second study vaccination with A/H7N9 vaccine with or without AS03), compared to baseline assessments performed prior to each study vaccination (Days -7, 1, and 29).
Detailed Description
This is a single center, randomized, partially-blinded, Phase II, small, targeted, prospective study in approximately 30 healthy male and non-pregnant female subjects aged 18 to 49 years old, inclusive, designed to evaluate and compare the immunogenicity between an intramuscular monovalent inactivated influenza A/H7N9 virus vaccine manufactured by Sanofi Pasteur given with and without AS03 adjuvant manufactured by GlaxoSmithKline, and an intramuscular unadjuvanted monovalent inactivated influenza A/H3N2v virus vaccine manufactured by Sanofi Pasteur. The primary objectives are (1) assessing the serum anti-HA hemagglutination-inhibition (HAI) response to influenza A/H7N9 antigen (with and without adjuvant) at Day 57 (approximately one month after the second study vaccination with A/H7N9 vaccine with or without AS03) and influenza A/H3N2v antigen at Day 29 (approximately one month after the study vaccination with A/H3N2v), and (2) identifying differentially expressed genes in human immune cells on Days 2, 4, and 29 (following the first study vaccination with A/H7N9 vaccine with or without AS03) and on Days 30, 32, and 36 (following the second study vaccination with A/H7N9 vaccine with or without AS03), compared to baseline assessments performed prior to each study vaccination (Days -7, 1, and 29). The secondary objectives are: (1) compare plasma cytokine and chemokine profiles at specific time points and between treatment arms at post vaccination points, (2) assess the neutralizing antibody responses to influenza A/H7N9 antigen (with and without adjuvant) at Day 57 (approximately one month after the second study vaccination with A/H7N9 vaccine with or without AS03) and influenza A/H3N2v antigen at Day 29 (approximately one month after the study vaccination with A/H3N2v vaccine), and (3) identify differentially expressed genes in human immune cells on Days 2, 4, and 8 following one intramuscular dose of influenza A/H3N2v vaccine compared to baseline assessments performed prior to study vaccination (Day -7 and Day 1).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Provide written informed consent prior to initiation of any study procedures.
- •Are able to understand and comply with planned study procedures and be available for all study visits.
- •Are males or non-pregnant females, 18 to 49 years old, inclusive.
- •Are in good health\*.
- •\*As determined by medical history and targeted physical examination, if indicated based on medical history, to evaluate acute or currently ongoing chronic medical diagnoses or conditions, defined as those that have been present for at least 90 days, that would affect the assessment of the safety of subjects or the immunogenicity of study vaccinations. Chronic medical diagnoses or conditions should be stable for the last 60 days. This includes no change in chronic prescription medication, dose, or frequency as a result of deterioration of the chronic medical diagnosis or condition in the 60 days prior to enrollment. Any prescription change that is due to change of health care provider, insurance company, etc., or that is done for financial reasons, as long as in the same class of medication, will not be considered a deviation of this inclusion criterion. Any change in prescription medication due to improvement of a disease outcome, as determined by the site principal investigator or appropriate sub-investigator, will not be considered a deviation of this inclusion criterion. Subjects may be on chronic or as needed (prn) medications if, in the opinion of the site principal investigator or appropriate sub-investigator, they pose no additional risk to subject safety or assessment of reactogenicity and immunogenicity and do not indicate a worsening of medical diagnosis or condition. Similarly, medication changes subsequent to enrollment and study vaccination are acceptable provided there was no deterioration in the subject's chronic medical condition that necessitated a medication change, and there is no additional risk to the subject or interference with the evaluation of responses to study vaccination. Note: Topical, nasal, and inhaled medications (with the exception of inhaled corticosteroids as outlined in the Subject Exclusion Criteria), herbals, vitamins, and supplements are permitted.
- •Oral temperature is less than 100.4 degrees F.
- •Pulse is 50 to 115 bpm, inclusive.
- •Systolic blood pressure is 85 to 150 mm Hg, inclusive.
- •Diastolic blood pressure is 55 to 95 mm Hg, inclusive.
- •Erythrocyte sedimentation rate (ESR) is less than 30 mm per hour.
Exclusion Criteria
- •Have an acute illness\*, as determined by the site principal investigator or appropriate sub-investigator, within 72 hours prior to study vaccination.
- •\*An acute illness which is nearly resolved with only minor residual symptoms remaining is allowable if, in the opinion of the site principal investigator or appropriate sub-investigator, the residual symptoms will not interfere with the ability to assess safety parameters as required by the protocol.
- •Have any medical disease or condition that, in the opinion of the site principal investigator or appropriate sub-investigator, is a contraindication to study participation\*.
- •\*Including acute or chronic medical disease or condition, defined as persisting for at least 90 days that would place the subject at an unacceptable risk of injury, render the subject unable to meet the requirements of the protocol, or may interfere with the evaluation of responses or the subject's successful completion of this study.
- •Have immunosuppression as a result of an underlying illness or treatment, or use of anticancer chemotherapy or radiation therapy (cytotoxic) within 3 years prior to study vaccination.
- •Have known active neoplastic disease (excluding non-melanoma skin cancer) or a history of any hematologic malignancy.
- •Have known human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infection.
- •Have known hypersensitivity or allergy to eggs, egg or chicken protein, squalene-based adjuvants, or other components of the study vaccines.
- •Have a history of severe reactions following previous immunization with licensed or unlicensed influenza virus vaccines.
- •Have a personal or family history of narcolepsy.
Arms & Interventions
Arm 1
10 Subjects: one dose of 15 µg of A/H3N2v, at Day 1
Intervention: Influenza Virus Vaccine, Monovalent A/H3N2v A/Minnesota/11/2010 NYMC X-203
Arm 2
10 Subjects: two doses of 3.75 µg of AH7N9 AS03,at Day 1 and at Day 29
Intervention: AS03
Arm 2
10 Subjects: two doses of 3.75 µg of AH7N9 AS03,at Day 1 and at Day 29
Intervention: Monovalent influenza A/H7N9 virus vaccine
Arm 3
10 Subjects: two doses of 3.75 µg of A/H7N9, at Day 1 and Day 29
Intervention: Monovalent influenza A/H7N9 virus vaccine
Outcomes
Primary Outcomes
Number of Differentially Expressed Genes Based on RNA Expression in Human Immune Cells (A/H7N9 Vaccine, With and Without Adjuvant)
Time Frame: Days 2, 4, and 29 Post-Vaccination 1 (Day 2, 4, and 29, respectively); Days 2, 4, and 8 Post-Vaccination 2 (Day 30, 32, and 36, respectively)
RNA expression levels (read counts) for each gene were determined by RNA-Sequencing of RNA extracted from six separated cell types: monocytes , dendritic cells, neutrophils, NK cells, B cells, and T cells. Post-vaccination gene expression levels were compared to pre-vaccination gene expression levels (combined summed read counts for Day -7 and Day 1 samples for post-vaccination 1 timepoints and Day 29 read counts for post-vaccination 2 timepoints) using a negative binomial model to identify differentially expressed (DE) genes (FDR-adjusted p-value \< 0.05 and mean fold change =\> 1.5 in either direction).
Percentage of Participants Achieving Seroconversion Based on HAI Titer (A/H3N2v Vaccine)
Time Frame: Day 29 Post-Vaccination 1 (Day 29)
Seroconversion is defined as either a pre-vaccination HAI titer \<1:10 and a post-vaccination HAI titer =\>1:40 or a pre-vaccination HAI titer =\>1:10 and a minimum four-fold rise in post-vaccination HAI antibody titer. Venous blood samples for serum were used for this assay. HAI based on the H3N2 strain A/Minnesota/11/2010 were assessed.
Percentage of Participants Achieving Seroconversion Based on HAI Titer (A/H7N9 Vaccine, With and Without Adjuvant)
Time Frame: Day 29 Post-Vaccination 2 (Day 57)
Seroconversion is defined as either a pre-vaccination HAI titer \<1:10 and a post-vaccination HAI titer =\>1:40 or a pre-vaccination HAI titer =\>1:10 and a minimum four-fold rise in post-vaccination HAI antibody titer. Venous blood samples for serum were used for this assay. HAI based on the H7N9 strain A/Shanghai/02/2013xPR8 were assessed.
Secondary Outcomes
- Cytokine and Chemokine Concentration by Study Arm and Study Visit Day - Part 3(Day 1 Pre-Vaccination 1; Days 2, 4, 8, and 29 Post-Vaccination 1 (Day 2, 4, 8, and 29, respectively); Days 2, 4, and 8 Post-Vaccination 2 (Day 30, 32, and 36, respectively))
- Geometric Mean Titers of Serum Neut Antibody (A/H7N9 Vaccine, With and Without Adjuvant)(Day 1 Pre-Vaccination 1 (Day 1), Day 29 Post-Vaccination 1 (Day 29), and Day 29 Post-Vaccination 2 (Day 57))
- Fold Change in Cytokine and Chemokine Concentrations From Pre-vaccination - Part 2(Days 2, 4, 8, and 29 Post-Vaccination 1 (Day 2, 4, 8, and 29, respectively); Days 2, 4, and 8 Post-Vaccination 2 (Day 30, 32, and 36, respectively))
- Percentage of Participants Achieving Seroconversion Based on Neut Titer (A/H3N2v Vaccine)(Day 29 Post-Vaccination 1 (Day 29))
- Cytokine and Chemokine Concentration by Study Arm and Study Visit Day - Part 2(Day 1 Pre-Vaccination 1; Days 2, 4, 8, and 29 Post-Vaccination 1 (Day 2, 4, 8, and 29, respectively); Days 2, 4, and 8 Post-Vaccination 2 (Day 30, 32, and 36, respectively))
- Geometric Mean Titers of Serum HAI Antibody (A/H7N9 Vaccine, With and Without Adjuvant)(Day 1 Pre-Vaccination 1, Day 29 Post-Vaccination 1 (Day 29), and Day 29 Post-Vaccination 2 (Day 57))
- Cytokine and Chemokine Concentration by Study Arm and Study Visit Day - Part 1(Day 1 Pre-Vaccination 1; Days 2, 4, 8, and 29 Post-Vaccination 1 (Day 2, 4, 8, and 29, respectively); Days 2, 4, and 8 Post-Vaccination 2 (Day 30, 32, and 36, respectively))
- Number of Differentially Expressed Genes Based on RNA Expression in Human Immune Cells (A/H3N2v Vaccine)(Days 2, 4, and 8 Post-Vaccination 1 (Day 2, 4, and 8, respectively))
- Fold Change in Cytokine and Chemokine Concentrations From Pre-vaccination - Part 1(Days 2, 4, 8, and 29 Post-Vaccination 1 (Day 2, 4, 8, and 29, respectively); Days 2, 4, and 8 Post-Vaccination 2 (Day 30, 32, and 36, respectively))
- Percentage of Participants Achieving Seroconversion Based on Neut Titer (A/H7N9 Vaccine, With and Without Adjuvant)(Day 29 Post-Vaccination 2 (Day 57))
- Geometric Mean Titers of Serum HAI Antibody (A/H3N2v Vaccine)(Day 1 Pre-Vaccination 1 (Day 1), Day 29 Post-Vaccination 1 (Day 29))
- Geometric Mean Titers of Serum Neut Antibody (A/H3N2v Vaccine)(Day 1 Pre-Vaccination 1 (Day 1), Day 29 Post-Vaccination 1 (Day 29))