Safety and Immune Response to Recombinant Live-Attenuated Influenza H2N2 Virus Vaccine
Primary Purpose
Influenza, Virus Diseases
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
H2N2 1960 AA ca recombinant vaccine
Sponsored by
About this trial
This is an interventional prevention trial for Influenza focused on measuring Vaccine, Influenza
Eligibility Criteria
Inclusion Criteria:
- General good health
- Available for the duration of the trial
- If female, 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:
- Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, or renal disease. More information on this criterion can be found in the protocol.
- Behavioral or cognitive impairment or psychiatric disease that, in the opinion of the investigator, intereferes with the study
- Previous receipt of FluMist or any intranasal live attenuated influenza vaccine
- Previous enrollment in an H2N2 influenza vaccine trial or in any study of an avian influenza vaccine
- Seropositive to the H2N2 influenza A virus (serum HAI titer >1:8)
- Positive urine drug toxicology test indicating narcotic use and/or dependency as defined by the Drug Enforcement Agency
- Medical, occupational, or family problems as a result of alcohol or illicit drug use within the 12 months prior to study entry
- Any condition that, in the opinion of the investigator, would interfere with the study
- History of anaphylaxis
- Allergy to oseltamivir as determined by subject report
- Current diagnosis of asthma or reactive airway disease within 2 years prior to study entry
- History of Guillain-Barre Syndrome
- HIV-1-infected
- Hepatitis C-infected
- Positive hepatitis B virus surface antigen
- Known immunodeficiency syndrome
- Use of corticosteroids (excluding topical preparations) or immunosuppressive drugs within 30 days prior to study entry
- Receipt of a live vaccine within 4 weeks or a killed vaccine within 2 weeks prior to study entry
- History of a surgical splenectomy
- Receipt of blood or blood-derived products (including immunoglobulin) within 6 months prior to study entry
- 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 entry
- Travel on a cruise ship within 14 days prior to study entry
- Direct contact with live poultry within the 14 days prior to the study or after study completion.
- Receipt of another investigational vaccine or drug within 30 days prior to study entry
- Allergy to eggs or egg products
- Pregnant or breastfeeding
Sites / Locations
- Johns Hopkins Bayview Medical Center, CIR Unit at the Mason F Lord Building
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
1
Arm Description
Participants will receive 2 doses of vaccine 4 to 8 weeks (28-62 days) apart
Outcomes
Primary Outcome Measures
Frequency of vaccine-related reactogenicity events and other adverse events
Amount of vaccine virus shed by each participant
Amount of serum and nasal wash antibody induced by the vaccine
Secondary Outcome Measures
Number of participants infected with the H2N2 1960 AA ca recombinant vaccine
Phenotypic stability of vaccine virus shed
Determine whether immunogenicity is enhanced by a second dose of vaccine, and whether the first dose of vaccine restricts replication of the second dose
T-cell mediated and innate immune responses against the H2N2 1960 AA ca recombinant vaccine
Full Information
NCT ID
NCT00722774
First Posted
July 25, 2008
Last Updated
November 7, 2008
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Johns Hopkins Bloomberg School of Public Health
1. Study Identification
Unique Protocol Identification Number
NCT00722774
Brief Title
Safety and Immune Response to Recombinant Live-Attenuated Influenza H2N2 Virus Vaccine
Official Title
Phase I Inpatient Study of the Safety and Immunogenicity of Live Influenza A Vaccine H2N2 (A/Ann Arbor/6/60 ca Recombinant), a Live Attenuated Virus Vaccine Candidate for Prevention of Influenza H2N2 Infection in the Event of a Pandemic
Study Type
Interventional
2. Study Status
Record Verification Date
July 2008
Overall Recruitment Status
Completed
Study Start Date
undefined (undefined)
Primary Completion Date
September 2008 (Actual)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Johns Hopkins Bloomberg School of Public Health
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
In the 20th century, influenza pandemics occurred in 1918, 1957, and 1968, and were associated with significant morbidity and mortality. It is estimated that, in the United States alone, the next influenza pandemic could cause approximately 200,000 deaths and 750,000 hospitalizations. Thus, the development of a vaccine against potential influenza strains has become a priority. The purpose of this study is to determine the safety and immune response to an H2N2 influenza vaccine candidate.
Detailed Description
H2N2 influenza viruses emerged in the 1950s replacing the then circulating H1N1 human influenza virus. The first cases occurred in China in 1956, and disease became widespread in 1956-1957, resulting in the "Asian Influenza" pandemic that was responsible for between 1 and 4 million deaths worldwide. H2N2 viruses have not circulated since 1968, when they were replaced by H3N2 influenza viruses and the resurgence of H1N1 viruses. For this reason, a large proportion of the population is now susceptible to infection with H2N2 influenza. If this subtype re-emerges, it could potentially cause the next pandemic. This vaccine, therefore, is an important priority in the development of vaccines against potential pandemic influenza strains.
This vaccine trial will be conducted in the Center for Immunization Research isolation unit in the Mason F. Lord Building at the Johns Hopkins Bayview Medical Center (Baltimore, MD). The study will be initiated between April 1st and December 20th, 2008, when wild-type influenza is unlikely to be circulating in the Baltimore area.
An individual's participation in the study will last approximately 90 days. All participants will receive two vaccinations approximately 4 - 8 weeks apart. After each vaccination, participants will remain in isolation at the study site for at least nine days or until rRT-PCR assays for influenza are negative for 2 consecutive days. A physical examination and nasal wash will occur each day during the isolation period. Blood collection will occur in isolation beginning on Day 7 until release. Follow-up outpatient visits are scheduled on Days 28 and 56 after the first vaccination and on Day 28 after the second vaccination. Follow-up visits will include serum collection, nasal wash, and interim medical history.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Influenza, Virus Diseases
Keywords
Vaccine, Influenza
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
22 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Experimental
Arm Description
Participants will receive 2 doses of vaccine 4 to 8 weeks (28-62 days) apart
Intervention Type
Biological
Intervention Name(s)
H2N2 1960 AA ca recombinant vaccine
Intervention Description
Approximately 0.2 ml of 10^7 TCID50 doses of vaccine administered intranasally
Primary Outcome Measure Information:
Title
Frequency of vaccine-related reactogenicity events and other adverse events
Time Frame
Throughout study
Title
Amount of vaccine virus shed by each participant
Time Frame
Throughout study
Title
Amount of serum and nasal wash antibody induced by the vaccine
Time Frame
Throughout study
Secondary Outcome Measure Information:
Title
Number of participants infected with the H2N2 1960 AA ca recombinant vaccine
Time Frame
Throughout study
Title
Phenotypic stability of vaccine virus shed
Time Frame
Throughout study
Title
Determine whether immunogenicity is enhanced by a second dose of vaccine, and whether the first dose of vaccine restricts replication of the second dose
Time Frame
Throughout study
Title
T-cell mediated and innate immune responses against the H2N2 1960 AA ca recombinant vaccine
Time Frame
Throughout study
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
General good health
Available for the duration of the trial
If female, 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:
Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, or renal disease. More information on this criterion can be found in the protocol.
Behavioral or cognitive impairment or psychiatric disease that, in the opinion of the investigator, intereferes with the study
Previous receipt of FluMist or any intranasal live attenuated influenza vaccine
Previous enrollment in an H2N2 influenza vaccine trial or in any study of an avian influenza vaccine
Seropositive to the H2N2 influenza A virus (serum HAI titer >1:8)
Positive urine drug toxicology test indicating narcotic use and/or dependency as defined by the Drug Enforcement Agency
Medical, occupational, or family problems as a result of alcohol or illicit drug use within the 12 months prior to study entry
Any condition that, in the opinion of the investigator, would interfere with the study
History of anaphylaxis
Allergy to oseltamivir as determined by subject report
Current diagnosis of asthma or reactive airway disease within 2 years prior to study entry
History of Guillain-Barre Syndrome
HIV-1-infected
Hepatitis C-infected
Positive hepatitis B virus surface antigen
Known immunodeficiency syndrome
Use of corticosteroids (excluding topical preparations) or immunosuppressive drugs within 30 days prior to study entry
Receipt of a live vaccine within 4 weeks or a killed vaccine within 2 weeks prior to study entry
History of a surgical splenectomy
Receipt of blood or blood-derived products (including immunoglobulin) within 6 months prior to study entry
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 entry
Travel on a cruise ship within 14 days prior to study entry
Direct contact with live poultry within the 14 days prior to the study or after study completion.
Receipt of another investigational vaccine or drug within 30 days prior to study entry
Allergy to eggs or egg products
Pregnant or breastfeeding
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kawsar Talaat, MD
Organizational Affiliation
Johns Hopkins Bloomberg School of Public Health
Official's Role
Principal Investigator
Facility Information:
Facility Name
Johns Hopkins Bayview Medical Center, CIR Unit at the Mason F Lord Building
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21205
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
18582523
Citation
Eichelberger M, Golding H, Hess M, Weir J, Subbarao K, Luke CJ, Friede M, Wood D. FDA/NIH/WHO public workshop on immune correlates of protection against influenza A viruses in support of pandemic vaccine development, Bethesda, Maryland, US, December 10-11, 2007. Vaccine. 2008 Aug 12;26(34):4299-303. doi: 10.1016/j.vaccine.2008.06.012. Epub 2008 Jun 26.
Results Reference
background
PubMed Identifier
18618064
Citation
Hampson AW. Vaccines for pandemic influenza. The history of our current vaccines, their limitations and the requirements to deal with a pandemic threat. Ann Acad Med Singap. 2008 Jun;37(6):510-7.
Results Reference
background
PubMed Identifier
18550873
Citation
Wright PF. Vaccine preparedness--are we ready for the next influenza pandemic? N Engl J Med. 2008 Jun 12;358(24):2540-3. doi: 10.1056/NEJMp0803650. No abstract available.
Results Reference
background
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Safety and Immune Response to Recombinant Live-Attenuated Influenza H2N2 Virus Vaccine
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