Inactivated Influenza A/H5N1 Vaccine in Adult Subjects at Risk of Occupational Exposure to Live H5N1 Viruses

A Single Center, Open-label, Phase I/II Study of Two 90 Microgram Doses of Intramuscular Inactivated Influenza A/H5N1 Vaccine in Adult Subjects at Risk of Occupational Exposure to Live H5N1 Viruses

This is a single center, open-label, Phase I/II study in up to 100 adult subjects, aged 18 years and older who are at occupational risk of exposure to live H5N1 viruses. This study is designed to investigate the safety, reactogenicity, and immunogenicity of two 90 µg doses of an investigational inactivated influenza A/H5N1 virus vaccine given approximately 28 days apart. A blood sample will be collected for immunogenicity evaluation prior to each vaccination. Subjects will maintain a memory aid (appendix C4 and C13) to record oral temperature and systemic and local AEs for 7 days after immunization. Subjects will be encouraged to take their temperature around the same time each day. All subjects will receive a safety follow-up telephone call at 1 to 3 days after each vaccination (approximately Day 2) to elicit any AE and concomitant medication information. Subjects will return to the clinic 7 days after each vaccination for assessment of AEs and concomitant medications, a targeted physical examination (if indicated), and review of the memory aid. At approximately Day 28 after the first vaccination, subjects will return to the clinic for evaluation of vital signs, blood sample collection and safety follow-up, confirmation of eligibility criteria and a second vaccination. Safety follow-up will be identical to that performed after the first vaccination. At approximately Day 56 (or about 28 days after the second vaccination), subjects will return to the clinic for immunogenicity blood sample collection, AE and concomitant medication assessment, and targeted physical examination and vital sign assessment (if indicated). At approximately Day 180 (6 months after the first vaccination), subjects will return to the clinic for a final immunogenicity blood sample collection and safety assessment.

Blood samples collected prior to each vaccination (Days 0 and 28) and on Days 56 and 180 after the first vaccination will be tested at the CDC Influenza Division Laboratory for the levels of neutralizing and HAI antibodies and CMI responses.

The primary outcome measures will be the frequencies and severities of AEs and the GMTS and proportions of subjects who achieve 4-fold rises in serum neutralizing and HAI titers against the influenza A/H5N1 virus on Day 56. Serum HAI and neutralizing antibody responses (including frequencies of 4 fold or greater rise in titer; GMTs; and proportions of subjects achieving protective titers of neutralizing antibody 1 month and 6 months after first dose) will also be assessed. A secondary outcome measure will be CMI responses evaluated 1 month after the receipt of each dose of vaccine and 6 months after the receipt of the first dose of vaccine.

Study Overview

• Status: Unknown
• Conditions: Influenza
• Intervention / Treatment: Biological: inactivated influenza A/H5N1 vaccine

Detailed Description

This is a single center, open-label, Phase I/II study in up to 100 adult subjects, aged 18 years and older who are at occupational risk of exposure to live H5N1 viruses. This study is designed to investigate the safety, reactogenicity, and immunogenicity of two 90 µg doses of an investigational inactivated influenza A/H5N1 virus vaccine given approximately 28 days apart. A blood sample will be collected for immunogenicity evaluation prior to each vaccination. Subjects will maintain a memory aid (appendix C4 and C13) to record oral temperature and systemic and local AEs for 7 days after immunization. Subjects will be encouraged to take their temperature around the same time each day. All subjects will receive a safety follow-up telephone call at 1 to 3 days after each vaccination (approximately Day 2) to elicit any AE and concomitant medication information. Subjects will return to the clinic 7 days after each vaccination for assessment of AEs and concomitant medications, a targeted physical examination (if indicated), and review of the memory aid. At approximately Day 28 after the first vaccination, subjects will return to the clinic for evaluation of vital signs, blood sample collection and safety follow-up, confirmation of eligibility criteria and a second vaccination. Safety follow-up will be identical to that performed after the first vaccination. At approximately Day 56 (or about 28 days after the second vaccination), subjects will return to the clinic for immunogenicity blood sample collection, AE and concomitant medication assessment, and targeted physical examination and vital sign assessment (if indicated). At approximately Day 180 (6 months after the first vaccination), subjects will return to the clinic for a final immunogenicity blood sample collection and safety assessment.

Blood samples collected prior to each vaccination (Days 0 and 28) and on Days 56 and 180 after the first vaccination will be tested at the CDC Influenza Division Laboratory for the levels of neutralizing and HAI antibodies and CMI responses.

The primary outcome measures will be the frequencies and severities of AEs and the GMTS and proportions of subjects who achieve 4-fold rises in serum neutralizing and HAI titers against the influenza A/H5N1 virus on Day 56. Serum HAI and neutralizing antibody responses (including frequencies of 4 fold or greater rise in titer; GMTs; and proportions of subjects achieving protective titers of neutralizing antibody 1 month and 6 months after first dose) will also be assessed. A secondary outcome measure will be CMI responses evaluated 1 month after the receipt of each dose of vaccine and 6 months after the receipt of the first dose of vaccine.

• Study Type: Interventional
• Enrollment (Actual): 55
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30333
      • Centers for Disease Control and Prevention

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Non-pregnant
• Non-immune compromised adults 18 years and older
• At occupational risk of exposure to live H5N1 viruses
• Must be eligible for care by the CDC occupational health clinic

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Influenza A/H5N1 Vaccine; Two 90ug Doses of Intramuscular Inactivated Influenza A/H5N1 Vaccine	Biological: inactivated influenza A/H5N1 vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The primary outcome measures will be the frequencies and severities of AEs and the GMTS and proportions of subjects who achieve 4-fold rises in serum neutralizing and HAI titers against the influenza A/H5N1 virus.	28 days, 56 days, 180 days

Collaborators and Investigators

• Sponsor: Centers for Disease Control and Prevention
• Investigators: Principal Investigator: Carolyn Bridges, MD, Centers for Disease Control and Prevention

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Primary Completion (Actual): December 1, 2007
• Study Completion (Anticipated): January 1, 2013

Study Registration Dates

• First Submitted: December 28, 2006
• First Submitted That Met QC Criteria: December 29, 2006
• First Posted (Estimate): January 1, 2007

Study Record Updates

• Last Update Posted (Estimate): September 7, 2012
• Last Update Submitted That Met QC Criteria: September 6, 2012
• Last Verified: September 1, 2012

More Information

Terms related to this study

• Keywords: vaccine; H5N1; Influenza A/H5N1; avian influenza H5N1
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human; Influenza in Birds
• Other Study ID Numbers: CDC-NCIRD-5000