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Evaluation of the Safety and Immunogenicity of a Live Attenuated Virus Vaccine for the Prevention of H2N3 Influenza

Primary Purpose

Influenza A Virus Infection

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

H2N3 MO 2003/AA ca Vaccine

About this trial

This is an interventional prevention trial for Influenza A Virus Infection

Eligibility Criteria

18 Years - 42 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

In general good health, without significant medical illness, physical examination findings, or significant laboratory abnormalities as determined by the investigator
Agree to storage of blood specimens for future research
Available for the duration of the trial
Willing to participate in the study as evidenced by signing the informed consent document
Female participants must agree to use effective birth control methods for the duration of the study. More information on this criterion can be found in the protocol.

Exclusion Criteria:

Pregnant or breastfeeding
Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, or renal disease by history, physical examination, and/or laboratory studies including urine testing. Clinically significant alanine aminotransferase (ALT) levels, as determined by the principal investigator (PI), will be exclusionary at baseline, prior to vaccination.
Behavioral or cognitive impairment or psychiatric disease that in the opinion of the investigator affects the ability of the participant to understand and cooperate with the study procedures
Previous enrollment in an H2 influenza vaccine trial or in any study of an avian influenza vaccine
Seropositive to the H2N3 influenza A virus (serum HAI titer greater than 1:8)
Positive urine drug toxicology test indicating narcotic use/dependency
Have medical, occupational, or family problems as a result of alcohol or illicit drug use during the 12 months prior to study entry
Other condition that, in the opinion of the investigator, would jeopardize the safety or rights of a person participating in the trial or would render the person unable to comply with the study procedures
History of anaphylaxis
Allergy to oseltamivir as determined by participant report
Current diagnosis of asthma or reactive airway disease (within the 2 years prior to study entry)
History of Guillain-Barré Syndrome
Positive ELISA and confirmatory Western blot tests for human immunodeficiency virus-1 (HIV-1)
Positive ELISA and confirmatory test (e.g., recombinant immunoblot assay) for hepatitis C virus (HCV)
Positive hepatitis B virus surface antigen (HBsAg) by ELISA
Known immunodeficiency syndrome
Use of corticosteroids (excluding topical preparations) or immunosuppressive drugs within 30 days prior to vaccination
Receipt of a live vaccine within 4 weeks or a killed vaccine within 2 weeks prior to study vaccination
History of a surgical splenectomy
Receipt of blood or blood-derived products (including immunoglobulin) within 6 months prior to study vaccination
Current smoker unwilling to stop smoking for the duration of the study. More information on this criterion can be found in the protocol.
Travel to the Southern Hemisphere within 14 days prior to study vaccination
Travel on a cruise ship within 14 days prior to study vaccination
Receipt of another investigational vaccine or drug within 30 days prior to study vaccination
Allergy to eggs or egg products

Sites / Locations

University of Rochester Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

H2N3 MO 2003/AA ca Vaccine

Arm Description

Participants will receive a nasal spray administration of the H2N3 MO 2003/AA ca vaccine on Day 0 and Day 28.

Outcomes

Primary Outcome Measures

Frequency of vaccine-related reactogenicity events that occur during the acute monitoring (inpatient) phase of the study

Area under the curve (AUC) of nasal virus shedding after each dose of vaccine as assessed by liquid titration of nasal secretions on Madin Darby canine kidney (MDCK) cells at 33°C

Development of serum antibody assessed by either hemagglutination inhibition (HAI) or microneutralization (MN) assays

Secondary Outcome Measures

Development of a significant increase in nasal secretion hemagglutinin (HA)-specific antibody assessed by enzyme-linked immunosorbent assay (ELISA)

Development of greater than 200 influenza-specific interferon-gamma-secreting cells per million lymphocytes as assessed by enzyme-linked immuno spot assay (ELISPOT) on Day 28 after immunization

Detection of influenza-specific IgG or IgA secreting B cells on Day 7 following vaccination assessed by antibody secreting cells (ASC) assay

Full Information

NCT ID

NCT01175122

First Posted

August 3, 2010

Last Updated

February 8, 2013

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

1. Study Identification

Unique Protocol Identification Number

NCT01175122

Brief Title

Evaluation of the Safety and Immunogenicity of a Live Attenuated Virus Vaccine for the Prevention of H2N3 Influenza

Official Title

Phase 1 Evaluation of the Safety and Immunogenicity of Live Influenza A Vaccine H2N3 (6-2) AA ca Recombinant (A/Swine/Missouri/4296424/2006 (H2N3) x A/Ann Arbor/6/60 ca), a Live Attenuated Virus Vaccine Candidate for Prevention of Influenza H2N3 Infection in the Event of a Pandemic

Study Type

Interventional

2. Study Status

Record Verification Date

February 2013

Overall Recruitment Status

Completed

Study Start Date

September 2010 (undefined)

Primary Completion Date

April 2011 (Actual)

Study Completion Date

April 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

In recent years, influenza viruses that have traditionally infected animals have infected humans as well. The H2N3 influenza virus, which first appeared in pigs in the Midwest United States in 2006, may pose a potential health concern to humans. This study will evaluate the safety of and immune response to a vaccine designed to protect people from the H2N3 influenza virus.

Detailed Description

Animal influenza viruses, such as the H1N1 and H5N1 viruses, typically infect animals like birds or pigs, but these viruses can also infect humans. The recent outbreak of the H1N1 influenza virus demonstrates that it is possible for these viruses to cause a pandemic outbreak in humans. Researchers are specifically interested in evaluating vaccines for H2 viruses, as these viruses caused a pandemic outbreak in humans in the late 1950s to 1960s. In addition, over half of the world's current population has no previous exposure to related viruses, which means a pandemic outbreak could pose a serious health risk as many people would have no immunity against the virus. In 2006, an outbreak of H2N3 infection occurred in pigs in the Midwest United States. While no humans contracted the virus during that outbreak, it remains a concern for researchers in the event that the virus ever spreads to humans. The purpose of this study is to evaluate the safety and immunogenicity of two doses of an experimental H2N3 vaccine, H2N3 MO 2006/AA ca in healthy adults. This is a live attenuated vaccine, which means that participants will be exposed to small amounts of the H2N3 vaccine virus and will need to remain isolated for at least 12 days when receiving the vaccine to prevent spreading the virus to others. This study will enroll healthy adults. Participants will receive two doses of the vaccine, 4 weeks apart, and will stay in an isolation facility during both 12-day vaccination periods. Participants will be admitted to the isolation facility 2 days before they receive their first vaccination. They will receive one nasal spray administration of the vaccine and will be monitored for side effects. On various days while in the isolation facility, they will undergo a physical exam, blood and urine collection, and a nasal wash procedure. Participants will remain in the isolation facility for at least 9 days after receiving the vaccine and possibly longer, until the nasal wash tests negative for the vaccine virus for 2 consecutive days. Participants will be readmitted to the isolation facility 26 days after the first vaccination. They will receive a second vaccination and all study procedures will be repeated. Participants will attend study visits 56, 82, and 208 days after the first vaccination for follow-up health and safety monitoring, blood collection, and a nasal wash procedure.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Influenza A Virus Infection

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

20 (Actual)

8. Arms, Groups, and Interventions

Arm Title

H2N3 MO 2003/AA ca Vaccine

Arm Type

Experimental

Arm Description

Participants will receive a nasal spray administration of the H2N3 MO 2003/AA ca vaccine on Day 0 and Day 28.

Intervention Type

Biological

Intervention Name(s)

H2N3 MO 2003/AA ca Vaccine

Intervention Description

0.2 mL of H2N3 MO 2003/AA ca vaccine delivered by an Accuspray nasal spray device on Day 0 and Day 28

Primary Outcome Measure Information:

Title

Frequency of vaccine-related reactogenicity events that occur during the acute monitoring (inpatient) phase of the study

Time Frame

Measured through Day 37 or until participants are discharged from the isolation unit

Title

Area under the curve (AUC) of nasal virus shedding after each dose of vaccine as assessed by liquid titration of nasal secretions on Madin Darby canine kidney (MDCK) cells at 33°C

Time Frame

Measured after each vaccination

Title

Development of serum antibody assessed by either hemagglutination inhibition (HAI) or microneutralization (MN) assays

Time Frame

Measured after each vaccination

Secondary Outcome Measure Information:

Title

Development of a significant increase in nasal secretion hemagglutinin (HA)-specific antibody assessed by enzyme-linked immunosorbent assay (ELISA)

Time Frame

Measured until participants are discharged from the isolation unit

Title

Development of greater than 200 influenza-specific interferon-gamma-secreting cells per million lymphocytes as assessed by enzyme-linked immuno spot assay (ELISPOT) on Day 28 after immunization

Time Frame

Measured 28 days after vaccination

Title

Detection of influenza-specific IgG or IgA secreting B cells on Day 7 following vaccination assessed by antibody secreting cells (ASC) assay

Time Frame

Measured 7 days after vaccination

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

42 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: In general good health, without significant medical illness, physical examination findings, or significant laboratory abnormalities as determined by the investigator Agree to storage of blood specimens for future research Available for the duration of the trial Willing to participate in the study as evidenced by signing the informed consent document Female participants must agree to use effective birth control methods for the duration of the study. More information on this criterion can be found in the protocol. Exclusion Criteria: Pregnant or breastfeeding Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, or renal disease by history, physical examination, and/or laboratory studies including urine testing. Clinically significant alanine aminotransferase (ALT) levels, as determined by the principal investigator (PI), will be exclusionary at baseline, prior to vaccination. Behavioral or cognitive impairment or psychiatric disease that in the opinion of the investigator affects the ability of the participant to understand and cooperate with the study procedures Previous enrollment in an H2 influenza vaccine trial or in any study of an avian influenza vaccine Seropositive to the H2N3 influenza A virus (serum HAI titer greater than 1:8) Positive urine drug toxicology test indicating narcotic use/dependency Have medical, occupational, or family problems as a result of alcohol or illicit drug use during the 12 months prior to study entry Other condition that, in the opinion of the investigator, would jeopardize the safety or rights of a person participating in the trial or would render the person unable to comply with the study procedures History of anaphylaxis Allergy to oseltamivir as determined by participant report Current diagnosis of asthma or reactive airway disease (within the 2 years prior to study entry) History of Guillain-Barré Syndrome Positive ELISA and confirmatory Western blot tests for human immunodeficiency virus-1 (HIV-1) Positive ELISA and confirmatory test (e.g., recombinant immunoblot assay) for hepatitis C virus (HCV) Positive hepatitis B virus surface antigen (HBsAg) by ELISA Known immunodeficiency syndrome Use of corticosteroids (excluding topical preparations) or immunosuppressive drugs within 30 days prior to vaccination Receipt of a live vaccine within 4 weeks or a killed vaccine within 2 weeks prior to study vaccination History of a surgical splenectomy Receipt of blood or blood-derived products (including immunoglobulin) within 6 months prior to study vaccination Current smoker unwilling to stop smoking for the duration of the study. More information on this criterion can be found in the protocol. Travel to the Southern Hemisphere within 14 days prior to study vaccination Travel on a cruise ship within 14 days prior to study vaccination Receipt of another investigational vaccine or drug within 30 days prior to study vaccination Allergy to eggs or egg products

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

John Treanor, MD

Organizational Affiliation

University of Rochester

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Rochester Medical Center

City

Rochester

State/Province

New York

ZIP/Postal Code

14642

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

18093945

Citation

Ma W, Vincent AL, Gramer MR, Brockwell CB, Lager KM, Janke BH, Gauger PC, Patnayak DP, Webby RJ, Richt JA. Identification of H2N3 influenza A viruses from swine in the United States. Proc Natl Acad Sci U S A. 2007 Dec 26;104(52):20949-54. doi: 10.1073/pnas.0710286104. Epub 2007 Dec 18.

Results Reference

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PubMed Identifier

20504935

Citation

Chen GL, Lamirande EW, Yang CF, Jin H, Kemble G, Subbarao K. Evaluation of replication and cross-reactive antibody responses of H2 subtype influenza viruses in mice and ferrets. J Virol. 2010 Aug;84(15):7695-702. doi: 10.1128/JVI.00511-10. Epub 2010 May 26.

Results Reference

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Learn more about this trial

Evaluation of the Safety and Immunogenicity of a Live Attenuated Virus Vaccine for the Prevention of H2N3 Influenza

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