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

Phase 2
Completed
Conditions
A/Vietnam/H5N1 Influenza Virus
Interventions
Biological: 7.5 mcg H5N1 (stored as monobulk)
Biological: 15 mcg H5N1 (stored as monobulk)
Biological: 90 mcg H5N1 (stored in vials)
Biological: 90 mcg H5N1 (stored as monobulk)
Other: MF59
Other: MF59 (stored as monobulk)
Registration Number
NCT02680002
Lead Sponsor
Biomedical Advanced Research and Development Authority
Brief Summary

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

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).

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
422
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
15 mcg H5N1 (monobulk) Plus MF59 (vials)MF59Two 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
7.5 mcg H5N1 (monobulk) Plus MF59 (monobulk)7.5 mcg H5N1 (stored as monobulk)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
7.5 mcg H5N1 (monobulk) Plus MF59 (monobulk)MF59 (stored as monobulk)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
15 mcg H5N1 (monobulk) Plus MF59 (vials)15 mcg H5N1 (stored as monobulk)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
7.5 mcg H5N1 (monobulk) Plus MF59 (vials)7.5 mcg H5N1 (stored as monobulk)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
7.5 mcg H5N1 (monobulk) Plus MF59 (vials)MF59Two 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
90 mcg H5N1 (vials) without MF5990 mcg H5N1 (stored in vials)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
90 mcg H5N1 (monobulk) without MF5990 mcg H5N1 (stored as monobulk)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
15 mcg H5N1 (monobulk) Plus MF59 (monobulk)MF59 (stored as monobulk)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
15 mcg H5N1 (monobulk) Plus MF59 (monobulk)15 mcg H5N1 (stored as monobulk)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
Primary Outcome Measures
NameTimeMethod
Number of Occurences of Mild, Moderate, or Severe Solicited Local Symptoms During the 7 Days After Each Vaccination.Days 21 to 28

Occurence of mild, moderate, or severe solicited local symptoms during the 7 days (Days 21 to 28) following Dose 2

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.Days 21 to 28

Number of participants with \>=1 mild, moderate, or severe solicited local symptoms during the 7 days (Days 21 to 29) following Dose 2

Number of Participants With Mild, Moderate, or Severe Solicited Systemic Reactogenicity Symptoms During the 7 Days After Each Vaccination.Days 0 to 7

Number of participants with mild, moderate, or severe solicited systemic reactogenicity adverse events during the 7 days (Days 0 to 7) following Dose 1

Number of Participants With of Mild, Moderate, or Severe Solicited Systemic Reactogenicity Symptoms During the 7 Days After Each Vaccination.Days 21 to 28

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

Geometric Mean Titer (GMT) of Hemagglutination Inhibition (HAI) Antibody21 days after receipt of second dose of vaccine (Day 42) (plus or minus 3 days)

Geometric Mean Titer (GMT) of hemagglutination inhibition (HAI) antibody against A/Vietnam/H5N1 antigen in each study group

Secondary Outcome Measures
NameTimeMethod
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 adverse events of special interest (AESI) or adverse events (AE) leading to study withdrawal.

Number of Participants With Unsolicited Adverse Events (AE)Day 0 (Visit 1) through Day 201 (Visit 8)

Number of participants with unsolicited adverse events (AE) through Visit 8 (Day 201)

Frequency of Unsolicited Adverse Events (AE)21 days following each vaccination (Days 0-21, >21 Days)

Frequency of unsolicited adverse events (AE) for 21 days following Dose 1 (Days 0-21) and after Dose 2 (\>21 Days)

Occurrence of Clinical Safety Laboratory AEs7 and 21 days after each vaccination (Days 0, 7, 21, 28, and 42)

Occurrence of clinical safety laboratory AEs at 7 and 21 days after each vaccination

Number of Participants With Vaccine-associated Serious Adverse Events (SAE) or Adverse Event of Special Interests (AESI)First vaccination through 13 months

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

GMT (Geometric Mean Titers) of Serum HAI (Hemagglutination Inhibition) AntibodiesDay 0 (Visit 1), Day 21 (Visit 4), Day 28 (Visit 6), Day 201 (Visit 8)

Overall GMTs of HAI antibodies at baseline (Day 0) and Days 21, 28 and 201

GMT (Geometric Mean Titers) of Serum Microneutralization (MN) AntibodiesDay 0 (Visit 1), Day 21 (Visit 4), Day 28 (Visit 6), Day 42 (Visit 7), Day 201 (Visit 8)

GMT of serum MN antibodies at baseline (Day 0) and Days 21, 28, 42 and 201

Serum HAI (Hemagglutination Inhibition) Titer of at Least 1:40Days 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)

Proportion of participants achieving a serum HAI titer of at least 1:40 against the A/Vietnam/H5N1 antigen

Seroconversion Rate (SCR) for Hemagglutination Inhibition (HAI) AntibodiesDays 21, 28, 42, and 201

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.

Seroconversion Rate (SCR) for Microneutralization (MN) AntibodiesDays 21, 28, 42, and 201

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.

Trial Locations

Locations (5)

Radiant Research, Inc.

🇺🇸

Edina, Minnesota, United States

Johnson County Clin-Trials, Inc.

🇺🇸

Lenexa, Kansas, United States

Central Kentucky Researcch Associates, Inc.

🇺🇸

Lexington, Kentucky, United States

Rochester Clinical Research, Inc.

🇺🇸

Rochester, New York, United States

Clinical Research Advantage, Inc./Ridge Family Practice

🇺🇸

Council Bluffs, Iowa, United States

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