Assess the Safety & Immunogenicity of Stored Inactivated Influenza H5N1 Virus Vaccine Given With & Without Stored MF59 Adjuvant

Study Overview
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Brief Summary
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The main purpose of this study is to assess the usability of long-term stored H5N1 antigen and adjuvant. The study is designed to assist in stockpile management by assessing the safety, reactogenicity, and immunogenicity long-term stored influenza A/Vietnam/H5N1 vaccine when administered with or without MF59® adjuvant.

Detailed Description
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This study is a randomized, double-blinded, Phase 2 study to assess the safety and immunogenicity of 2 doses of long-term stored inactivated monovalent influenza A/Vietnam/H5N1 virus vaccine administered intramuscularly with or without MF59 adjuvant in healthy males and nonpregnant females, aged 18 to 49 years, inclusive. This study is designed to assist in stockpile management and will assess the usability of long-term stored H5N1 antigen (ie, stored >10 years) and adjuvant (ie, stored >5 years).

Official Title
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Randomized, Double-Blinded, Phase 2 Study to Assess Safety & Immunogenicity of Stored Inactivated Monovalent Influenza A/Vietnam/H5N1 Virus Vaccine Administered Intramuscularly at Different Dose Levels Given With & Without Stored MF59® Adjuvant

Conditions
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A/Vietnam/H5N1 Influenza Virus

Intervention / Treatment
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* Biological: 7.5 mcg H5N1 (stored as monobulk)
* Biological: 15 mcg H5N1 (stored as monobulk)
* Biological: 90 mcg H5N1 (stored as monobulk)
* Biological: 90 mcg H5N1 (stored in vials)
* Other: MF59
* Other: MF59 (stored as monobulk)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or nonpregnant female Provide written informed consent prior to study-related procedures Stable health status Access to consistent and reliable means of telephone contact Able to understand and comply with planned study procedures Agree to stay in contact with site, and no plans to move from study area for study duration Exclusion Criteria: Allergic to eggs, other vaccine components, or squalene-based adjuvants Women with positive pregnancy test within 24 hours of vaccination, or are breastfeeding Females of childbearing potential who refuse acceptable birth control, if sexually active, have not used birth control for 2 months prior to study entry Have immunosuppression or use anticancer chemotherapy or radiation therapy within preceding 36 months Have an active neoplastic disease or history of hematologic malignancy Have long term use (≥14 consecutive days) of glucocorticoids (>20 mg/day) or high-dose inhaled steroids (>800 mcg/day) within preceding 6 months Diagnosis of schizophrenia, bipolar disease, or major psychiatric diagnosis Have been hospitalized for psychiatric illness, attempted suicide or deemed danger to self or others within past 10 years

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 7.5 mcg H5N1 (monobulk) Plus MF59 (monobulk)<br>Two 0.5-mL doses, given at Day 0 and 21 consisting of 7.5 mcg hemagglutinin (HA) antigen stored long-term as monobulk inactivated | Biological: 7.5 mcg H5N1 (stored as monobulk)<br> <br> Other: MF59 (stored as monobulk)<br> <br> |
| Experimental: 15 mcg H5N1 (monobulk) Plus MF59 (monobulk)<br>Two 0.5-mL doses, given at Day 0 and 21 consisting of 15 mcg HA antigen stored long-term as monobulk inactivated A/Vietnam/H5N1 vaccine and MF59 stored long-term as monobulk MF59 adjuvant | Biological: 15 mcg H5N1 (stored as monobulk)<br> <br> Other: MF59 (stored as monobulk)<br> <br> |
| Experimental: 7.5 mcg H5N1 (monobulk) Plus MF59 (vials)<br>Two 0.5-mL doses, given at Day 0 and 21 consisting of 7.5 mcg HA antigen stored long-term as monobulk inactivated A/Vietnam/H5N1 vaccine and MF59 stored short-term in vials as MF59 adjuvant | Biological: 7.5 mcg H5N1 (stored as monobulk)<br> <br> Other: MF59<br> <br> |
| Experimental: 15 mcg H5N1 (monobulk) Plus MF59 (vials)<br>Two 0.5-mL doses, given at Day 0 and 21 consisting of 15 mcg HA antigen stored long-term as monobulk inactivated A/Vietnam/H5N1 vaccine and MF59 stored short-term in vials as MF59 adjuvant | Biological: 15 mcg H5N1 (stored as monobulk)<br> <br> Other: MF59<br> <br> |
| Experimental: 90 mcg H5N1 (monobulk) without MF59<br>Two 1.0-mL doses at Day 0 and 21 consisting of 90 mcg HA antigen stored long-term as monobulk inactivated A/Vietnam/H5N1 antigen formulated and filled in 2015, administered without MF59 | Biological: 90 mcg H5N1 (stored as monobulk)<br> <br> |
| Experimental: 90 mcg H5N1 (vials) without MF59<br>Two 1.0-mL doses at Day 0 and 21 consisting of 90 mcg HA antigen stored long-term in vials as inactivated A/Vietnam/H5N1 vaccine, administered without MF59 | Biological: 90 mcg H5N1 (stored in vials)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Occurences of Mild, Moderate, or Severe Solicited Local Symptoms During the 7 Days After Each Vaccination. | Occurence of mild, moderate, or severe solicited local symptoms during the 7 days (Days 0 to 7) following Dose 1 | Days 0 to 7 | 
| Number of Occurences of Mild, Moderate, or Severe Solicited Local Symptoms During the 7 Days After Each Vaccination. | Occurence of mild, moderate, or severe solicited local symptoms during the 7 days (Days 21 to 28) following Dose 2 | Days 21 to 28 | 
| Number of Participants With >=1 (More Than or Equal to 1) Mild, Moderate, or Severe Solicited Local Symptoms During the 7 Days After Each Vaccination. | Number of participants with >=1 mild, moderate, or severe solicited local symptoms during the 7 days (Days 0 to 7) following Dose 1 | Days 0 to 7 | 
| Number of Participants With >=1 (More Than or Equal to 1) Mild, Moderate, or Severe Solicited Local Symptoms During the 7 Days After Each Vaccination. | Number of participants with >=1 mild, moderate, or severe solicited local symptoms during the 7 days (Days 21 to 29) following Dose 2 | Days 21 to 28 | 
| Number of Participants With Mild, Moderate, or Severe Solicited Systemic Reactogenicity Symptoms During the 7 Days After Each Vaccination. | Number of participants with mild, moderate, or severe solicited systemic reactogenicity adverse events during the 7 days (Days 0 to 7) following Dose 1 | Days 0 to 7 | 
| Number of Participants With of Mild, Moderate, or Severe Solicited Systemic Reactogenicity Symptoms During the 7 Days After Each Vaccination. | Number of participants with of mild, moderate, or severe solicited systemic reactogenicity adverse events during the 7 days (Days 21 to 28) following Dose 2 | Days 21 to 28 | 
| Geometric Mean Titer (GMT) of Hemagglutination Inhibition (HAI) Antibody | Geometric Mean Titer (GMT) of hemagglutination inhibition (HAI) antibody against A/Vietnam/H5N1 antigen in each study group | 21 days after receipt of second dose of vaccine (Day 42) (plus or minus 3 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Vaccine-associated Serious Adverse Events (SAE) or Adverse Event of Special Interests (AESI) | Number of participants with vaccine-associated serious adverse events (SAE) or adverse event of special interests (AESI) and occurence of AESIs or AEs leading to study withdrawal | First vaccination through 13 months | 
| Number of Participants With Adverse Events of Special Interest (AESI) or Adverse Events (AE) Leading to Study Withdrawal. | Number of participants with adverse events of special interest (AESI) or adverse events (AE) leading to study withdrawal. | First vaccination through approximately 13 months after first vaccination | 
| Number of Participants With Unsolicited Adverse Events (AE) | Number of participants with unsolicited adverse events (AE) through Visit 8 (Day 201) | Day 0 (Visit 1) through Day 201 (Visit 8) | 
| Frequency of Unsolicited Adverse Events (AE) | Frequency of unsolicited adverse events (AE) for 21 days following Dose 1 (Days 0-21) and after Dose 2 (>21 Days) | 21 days following each vaccination (Days 0-21, >21 Days) | 
| Occurrence of Clinical Safety Laboratory AEs | Occurrence of clinical safety laboratory AEs at 7 and 21 days after each vaccination | 7 and 21 days after each vaccination (Days 0, 7, 21, 28, and 42) | 
| GMT (Geometric Mean Titers) of Serum HAI (Hemagglutination Inhibition) Antibodies | Overall GMTs of HAI antibodies at baseline (Day 0) and Days 21, 28 and 201 | Day 0 (Visit 1), Day 21 (Visit 4), Day 28 (Visit 6), Day 201 (Visit 8) | 
| GMT (Geometric Mean Titers) of Serum Microneutralization (MN) Antibodies | GMT of serum MN antibodies at baseline (Day 0) and Days 21, 28, 42 and 201 | Day 0 (Visit 1), Day 21 (Visit 4), Day 28 (Visit 6), Day 42 (Visit 7), Day 201 (Visit 8) | 
| Serum HAI (Hemagglutination Inhibition) Titer of at Least 1:40 | Proportion of participants achieving a serum HAI titer of at least 1:40 against the A/Vietnam/H5N1 antigen | Days 0 (Visit 1), 21 (Visit 4, +1day), 28 (Visit 6, +1 day), 42 (Visit 7, plus or minus 3 days), and 201 (Visit 8, plus or minus 7 days) | 
| Seroconversion Rate (SCR) for Hemagglutination Inhibition (HAI) Antibodies | Defined as proportion of subjects achieving either a prevaccination HAI titer of <1:10 and postvaccination titer of at least 1:40 or a prevaccination HAI titer of at least 1:10 and a 4-fold or greater increase of HAI postvaccination antibody titers against the A/Vietnam/H5N1 antigen; if baseline HAI titer is undetectable, it will be assigned a vaue of half the lower limit of detection. | Days 21, 28, 42, and 201 | 
| Seroconversion Rate (SCR) for Microneutralization (MN) Antibodies | Defined as proportion of subjects achieving either a prevaccination MN titer of <1:10 and postvaccination titer of at least 1:40 or a prevaccination MN titer of at least 1:10 and a 4-fold or greater increase of MN postvaccination antibody titers against the A/Vietnam/H5N1 antigen; if baseline MN titer is undetectable, it will be assigned a vaue of half the lower limit of detection. | Days 21, 28, 42, and 201 |