Reverse Genetic H9N2 Influenza Vaccine Study in Adults

Study Overview
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Brief Summary
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The purpose of the study is to identify the optimal dose level of a reverse genetic (RG) reassortant H9N2 pandemic influenza vaccine for further product development.

Official Title
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A Randomized, Double Blind, Multi-center, Phase 1/2 Study to Assess Safety and Immunogenicity of Five Dose Levels of a Reverse Genetic (RG) Reassortant H9N2 Pandemic Influenza Vaccine in Healthy Subjects Aged 18 to 49 Years

Conditions
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Influenza

Intervention / Treatment
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* Biological: Reverse Genetic (RG) reassortant A/H9N2 influenza vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is 18 to 49 years of age, inclusive, on the day of screening Subject has an understanding of the study and its procedures, agrees to its provisions, and gives written informed consent prior to study entry Subject is generally healthy, as determined by the investigator's clinical judgement through collection of medical history and performance of a physical examination Subject is physically and mentally capable of participating in the study as determined by the investigator Subject agrees to keep a daily record of symptoms for the duration of the study If female of childbearing potential, subject presents with a negative urine pregnancy test within 24 hours prior to first vaccination and agrees to employ adequate birth control measures for the duration of the study. For the purposes of this study at least one of the following types of US Food and Drug Administration (FDA) approved birth control measures shall be applied through completion of the Day 181 study visit: Hormonal types of birth control (such as implants or birth control pills) or an intrauterine device A barrier type of birth control measure (i.e. condoms, diaphragms, cervical caps, etc.) Exclusion Criteria: Subject has a history of exposure to H9N2 influenza virus or a history of vaccination with an H9N2 influenza vaccine Subject is at potential occupational risk of contracting H9N2 influenza infection (e.g. poultry workers) Subject currently suffers from or has a history of a significant (requiring hospitalization or change in intervention in past 6 months)neurological, cardiovascular, pulmonary (including asthma), hepatic, rheumatic, autoimmune, hematological, metabolic or renal disorder such as but not limited to: multiple sclerosis, lupus, Guillain-Barre syndrome as determined by the investigator Subject has a body temperature of >= 100.4 degrees Fahrenheit (>= 38.0 degrees Celsius) on the day of vaccination, by oral measurement. [NOTE: Subjects meeting this exclusion criterion may be rescheduled for vaccination and study entry at a later date provided: 1) body temperature measured orally has decreased to < 100.4 degrees Fahrenheit (< 38.0 degrees Celsius); 2) all other inclusion/exclusion criteria are met; 3) the rescheduled date is no more than 14 days past the initial screening assessments and date; and 4) the study site is still enrolling subjects and randomization is not closed] Subject has a Body Mass Index (BMI) >= 35 Subject has hypertension at screening that is graded as greater than Stage 1 (defined as a systolic pressure > 159 or diastolic pressure > 99 while seated and at rest (measurement shall be repeated twice before subject is excluded) Subject has clinically significant abnormal laboratory values at screening as determined by the investigator Subject tests positive for Human Immunodeficiency Virus (HIV), Hepatitis B surface Antigen (HBsAgs) or Hepatitis C Virus (HCV) Subject has any medically diagnosed or suspected immune deficient condition based on medical history and physical examination as determined by the investigator Subject has an immune compromising condition or disease, or is currently undergoing a form of treatment or was undergoing a form of treatment within 30 days prior to study entry that can be expected to influence immune response. Such treatment includes, but is not limited to, systemic or high dose inhaled (> 800 μg/day of beclomethasone dipropionate or equivalent) corticosteroids, radiation treatment or other immunosuppressive or cytotoxic drugs (use of inhaled and nasal steroids will be permitted) Subject has a history of severe (required immediate medical life threatening treatment and/or hospitalization) allergic reactions or anaphylaxis as determined by the investigator Subject has a rash, dermatologic condition or tattoos which may interfere with injection site reaction rating as determined by the investigator Subject has received any blood products (e.g. blood transfusion or immunoglobulins) within 90 days prior to study entry Subject has donated one or more units of blood (approximately 450 mL) or plasma within 30 days prior to study entry Subject has received any live vaccine within 4 weeks or an inactivated vaccine or a subunit vaccine within 2 weeks prior to vaccination in this study Subject has a functional or surgical asplenia Subject has a positive urine drug screen (unless the subject is currently prescribed the drug detected by a licensed health care provider and the continued administration of the drug would not otherwise exclude the subject from participation) Subject has a known or suspected problem with alcohol or drug abuse as determined by the investigator Subject is currently enrolled or has participated in another clinical study involving an investigational products (IP) or device within 30 days prior to study enrollment or is scheduled to participate in another clinical study involving an IP or device during the course of this study Subject is a member of the team conducting this study or is in a dependent relationship with one of the study team members. Dependent relationships include close relatives (i.e. children, partner/spouse, siblings, parents) as well as employees of the investigator or site personnel conducting the study If female, subject is pregnant or lactating at the time of study enrollment Any condition that in the opinion of the investigator would interfere with evaluation of the vaccine or interpretation of study results

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 49 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>50 subjects will be randomized 1:1:1:1:1 to 5 dose groups (10 subjects per treatment group) to receive 2 intramuscular injections of RG reassortant A/H9N2 influenza vaccine on Day 1 and Day 22 | Biological: Reverse Genetic (RG) reassortant A/H9N2 influenza vaccine<br>* Two intramuscular vaccinations; 5 dose groups: 3.75 µg, 7.5 µg, 15 µg, 30 µg or 45 µg HA antigen (strain A/H9N2/chicken/Hong Kong/G9/97; non-adjuvanted formulation<br>|
| Experimental: Cohort 2<br>After a safety data review of the first 50 subjects, a further 225 subjects will be randomized 1:1:1:1:1 to 5 dose groups and will receive 2 intramuscular injections of RG reassortant A/H9N2 influenza vaccine on Day 1 and Day 22 | Biological: Reverse Genetic (RG) reassortant A/H9N2 influenza vaccine<br>* Two intramuscular vaccinations; 5 dose groups: 3.75 µg, 7.5 µg, 15 µg, 30 µg or 45 µg HA antigen (strain A/H9N2/chicken/Hong Kong/G9/97; non-adjuvanted formulation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With a Hemagglutination Inhibition (HI) Antibody Response to the Vaccine Strain (A/H9N2/Chicken/Hong Kong/G9/97) Associated With Seroconversion 21 Days After the Second Vaccination |  | 21 days after 2nd vaccination | 
| Number of Subjects Achieving an HI Antibody Titer >= 1:40 21 Days After the Second Vaccination |  | 21 days after 2nd vaccination | 
| Number of Subjects With Injection Site and Systemic Reactions Within 7 Days After the First and Second Vaccination (Vacc) by Severity |  | 7 days after 1st and 2nd vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Achieving an HI Antibody Titer >= 1:40 21 Days After the First Vaccination |  | 21 days after 1st vaccination | 
| Number of Subjects With Antibody Response Associated With Protection 21 Days After the First and Second Vaccination Defined as Microneutralization (MN) Titer >= 1:20 |  | 21 days after 1st and 2nd vaccination | 
| Number of Subjects With Antibody Response Associated With Protection 21 Days After the First and Second Vaccination Defined as Single Radial Hemolysis (SRH) Area >= 25 mm2 |  | 21 days after 1st and 2nd vaccination | 
| Number of Participants With Antibody Response 21 Days After the First and Second Vaccination Measured by HI, MN and SRH Assays |  | 21 days after 1st and 2nd vaccination | 
| Fold Increase of Antibody Response 21 Days After the First and Second Vaccination as Compared to Baseline Measured by HI, MN and SRH Assays |  | 21 days after 1st and 2nd vaccination | 
| Number of Subjects With Seroconversion (as Defined for the Primary Immunogenicity Endpoint) Measured by HI Assay 21 Days After the First Vaccination as Compared to Baseline |  | 21 days after 1st vaccination | 
| Number of Subjects With Seroconversion Defined as a Minimum Fourfold Increase in Titer Measured by MN Assay 21 Days After the First and Second Vaccination as Compared to Baseline |  | 21 days after 1st and 2nd vaccination | 
| Number of Subjects With Seroconversion as Measured by SRH Assay 21 Days After the First and Second Vaccination |  | 21 days after 1st and 2nd vaccination | 
| Number of Subjects With Antibody Response Associated With Protection 180 Days After the First Vaccination as Measured by HI, MN and SRH Assays |  | 180 days after 1st vaccination | 
| Number of Subjects With Antibody Response 180 Days After the First Vaccination Measured by HI, MN and SRH Assays |  | 180 days after 1st vaccination | 
| Fold Increase of Antibody Response 180 Days After the First Vaccination as Compared to Baseline Measured by HI, MN and SRH Assays |  | 180 days after 1st vaccination | 
| Number of Subjects With Fever, Malaise and Shivering With Onset Within 7 Days After the First and Second Vaccination |  | 7 days after 1st and 2nd vaccination | 
| Frequency and Severity of Adverse Events (AEs) Observed During the Entire Study Period |  | Through study completion by all subjects, an average of 181 days (+/- 14 days) |