AzTrials
AzTrials

Influenza, HumanPhase 1NCT01674205

Study of Immune Responses in Healthy Adults Receiving Live Influenza Virus Vaccines

A Phase 1 study testing A/swine/Missouri/4296424/2006 (H2N3) x A/Ann Arbor/6/60 ca (H2N3 MO 2006/AA ca), A/chicken/Hong Kong/G9/97 (H9N2) x A/Ann Arbor/6/60 ca (H9N2 G9/AA ca) and 2012-2013 trivalent seasonal live attenuated influenza vaccine (FluMist®) in people with Influenza, Human, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This study seeks to understand the host factors that affect the replication and immune response of seasonal and candidate pandemic live attenuated influenza vaccine (LAIV) in humans and to develop biomarkers that can predict the viral shedding and immune response to LAIVs. Read more about this study

Who is it for?
Ages 18 to 42 yearsHealthy volunteers can take part
Conditions the study is for
Influenza, Human
What is being tested?
A/swine/Missouri/4296424/2006 (H2N3) x A/Ann Arbor/6/60 ca (H2N3 MO 2006/AA ca), A/chicken/Hong Kong/G9/97 (H9N2) x A/Ann Arbor/6/60 ca (H9N2 G9/AA ca) and 2012-2013 trivalent seasonal live attenuated influenza vaccine (FluMist®)
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
36 participants
Where
1 siteUnited States
Study dates
Sep 2012to Jun 2013
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 42 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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. For the inpatient component of the study, participants must be willing and able to remain within the Isolation Unit for the specified duration of confinement. For the outpatient component of the study, participants must be willing and able to make daily outpatient follow-up visits as specified by the protocol.
  • Willingness 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 (for example, pharmacologic contraceptives including oral, parenteral, and transcutaneous delivery; condoms with spermicide; diaphragm with spermicide; intrauterine device; abstinence from heterosexual intercourse; or surgical sterilization). All female participants will be considered being of child-bearing potential except those who have undergone hysterectomy and those in whom menopause occurred at least 1 year prior to the study.

Who cannot join

  • Pregnancy as determined by a positive human choriogonadotropin (beta-HCG) test
  • Currently 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, 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 subject to understand and cooperate with the study protocol
  • Previous enrollment in an H2 or H9 influenza vaccine trial or in any study of an avian influenza vaccine
  • For the inpatient arm, seropositive to the H2N3 influenza A virus or the H9N2 influenza A virus (serum HAI titer >1:8). For the outpatient arm, seropositive to the H3N2 component of seasonal LAIV (serum hemagglutination inhibition [HAI] titer greater than 1:8).
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  • 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 past 12 months
  • Other condition that in the opinion of the investigator would jeopardize the safety or rights of a participant participating in the trial or would render the subject unable to comply with the protocol
  • History of anaphylaxis
  • Allergy to oseltamivir as determined by subject report
  • Current diagnosis of asthma or reactive airway disease (within the past 2 years)
  • 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
  • A current smoker includes anyone stating he/she currently smokes any amount of a tobacco product
  • The decision to exclude a potential participant is determined by medical history and a clinician's clinical judgment based on the physical examination
  • After admission to the unit, nicotine patches will be provided to current smokers who request them for the inpatient portion of the study
  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Rochester Medical Center: Facility for Evaluation of Flu Vaccines

    Rochester, New York, 14642

Other trials in United States

About this study

Official title: Exploratory Evaluation of Host Biomarkers That Predict the Vaccine Virus Replication and Immunogenicity of Seasonal and Pandemic Formulations of Live Attenuated Influenza A Virus Vaccines Based on the A/Ann Arbor/6/60 ca Master Donor Virus (MDV)

This study seeks to understand the host factors that affect the replication and immune response of seasonal and candidate pandemic live attenuated influenza vaccine (LAIV) in humans and to develop biomarkers that can predict the viral shedding and immune response to LAIVs.

Read the detailed description

Influenza A viruses are widely distributed in nature and exist as many different subtypes. Pandemics of influenza can occur, and vaccine development is focused on those subtypes that are predicted to represent the greatest pandemic threat to the human population. This study seeks to understand the host factors that affect the replication and immune response of seasonal and candidate pandemic LAIVs in humans and to develop biomarkers that can predict the viral shedding and immune response to LAIVs.

Three vaccines will be evaluated: the licensed seasonal LAIV, with a focus on the H3N2 component; the H9N2 G9/AA ca vaccine, which is among the most immunogenic of the candidate pandemic LAIVs evaluated to date; and the H2N3 MO 2066/AA ca vaccine, which is among the least immunogenic of the candidate pandemic LAIVs evaluated to date. The seasonal LAIV will be evaluated in an outpatient setting, while the other two vaccines will be evaluated in an inpatient setting. In each setting, some participants will receive a placebo vaccine.

Study participants will be assigned to one of four groups. Participants who are seronegative to both H9N2 G9/AA ca and H2N3 MO 2006/AA ca viruses will be randomly assigned to receive one of those vaccines (Group 1: H9N2 G9/AA ca; Group 2: H2N3 MO 2006/AA ca) or placebo (Group 4) and will remain in an inpatient isolation facility. Participants who are seronegative to the H3 component of seasonal LAIV will be randomly assigned to receive either seasonal vaccine (Group 3) or placebo (Group 4) and will be followed as outpatients.

All participants will remain in the study for 56 days. Participants in the inpatient arms will be admitted on Day -2, will receive study vaccine on Day 0, and will undergo a basic history, physical examination, and nasal wash each day until discharge. On some study days, inpatient participants will undergo a blood collection and/or a nasal swab; at the screening visit and on Day -1 or Day -2, participants will give a urine sample.

Participants in the outpatient arms will receive study vaccine on Day 0 and will have study visits on Days 1, 2, 3, 4, 5, 6, 7, 14, 28, and 56. On Days 1 through 7, participants will undergo a basic history, physical examination, and nasal wash. On some visits, participants may undergo a blood collection and/or a nasal swab; at the screening visit and on Day -1, participants will give a urine sample. Unused blood or nasal wash samples will be stored and may be used in future research studies.

Being tested
A/swine/Missouri/4296424/2006 (H2N3) x A/Ann Arbor/6/60 ca (H2N3 MO 2006/AA ca), A/chicken/Hong Kong/G9/97 (H9N2) x A/Ann Arbor/6/60 ca (H9N2 G9/AA ca), 2012-2013 trivalent seasonal live attenuated influenza vaccine (FluMist®), Vaccine placebo (Leibovitz-15 [L-15]), Vaccine placebo (FluMist®)
Medical subject headings
Influenza, Human

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • A/swine/Missouri/4296424/2006 (H2N3) x A/Ann Arbor/6/60 ca (H2N3 MO 2006/AA ca)Biological

  • A/chicken/Hong Kong/G9/97 (H9N2) x A/Ann Arbor/6/60 ca (H9N2 G9/AA ca)Biological

  • 2012-2013 trivalent seasonal live attenuated influenza vaccine (FluMist®)Biological

  • Vaccine placebo (Leibovitz-15 [L-15])Biological

  • Vaccine placebo (FluMist®)Biological

Study groups in NCT01674205
Study groupRoleWhat they receive
Group 1 (Inpatient, H2N3 MO 2006/AA ca)ExperimentalParticipants will receive one dose of vaccine on Day 0, with 0.2 mL being delivered by Accuspray device (0.1 mL per nostril).
Receives: Biological: A/swine/Missouri/4296424/2006 (H2N3) x A/Ann Arbor/6/60 ca (H2N3 MO 2006/AA ca)
Group 2 (Inpatient, H9N2 G9/AA ca)ExperimentalParticipants will receive one dose of vaccine on Day 0, with 0.5 mL being delivered as nose drops (0.25 mL per nostril) using a sterile, needle-less tuberculin syringe.
Receives: Biological: A/chicken/Hong Kong/G9/97 (H9N2) x A/Ann Arbor/6/60 ca (H9N2 G9/AA ca)
Group 3 (Outpatient, seasonal LAIV [FluMist®])Experimental2012-2013 trivalent seasonal live attenuated influenza vaccine (FluMist®)
Receives: Biological: 2012-2013 trivalent seasonal live attenuated influenza vaccine (FluMist®)
Group 4 (Both inpatient and outpatient, placebo)Placebo comparatorParticipants will receive either the L-15 placebo delivered by nose drops or the FluMist® placebo delivered as a nasal spray.
Receives: Biological: Vaccine placebo (Leibovitz-15 [L-15]); Biological: Vaccine placebo (FluMist®)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Area under the curve (AUC) of nasal virus shedding after vaccine dose as assessed by liquid titration of nasal secretions on Madin Darby Canine Kidney (MDCK) cells

    Measured: Measured through Day 9

  2. Development of serum antibody as assessed by either HAI or microneutralization (MN) assays

    Measured: Measured through Day 56

Secondary outcomes (3)

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

    Measured: Measured through Day 56

  2. Detection of influenza-specific immunoglobulin G (IgG) or immunoglobulin A (IgA) secreting B cells assessed by antibody secreting cells (ASC) assay

    Measured: Measured at Day 7

  3. Development of greater than 200 influenza-specific interferon-gamma-secreting cells per million lymphocytes as assessed by enzyme-linked immunospot assay (ELISPOT)

    Measured: Measured at Day 28

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Aug 2012 (estimated)
  2. Study startSep 2012
  3. Primary completionJun 2013
  4. Study completionJun 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Basic science
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
36 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01674205
Sponsor's protocol ID
URMC 12-001
Status last verified
Oct 2015
First submitted
23 Aug 2012
Last updated
15 Dec 2015
Results posted
No
Data monitoring committee
No

Publications

  • Karron RA, Callahan K, Luke C, Thumar B, McAuliffe J, Schappell E, Joseph T, Coelingh K, Jin H, Kemble G, Murphy BR, Subbarao K. A live attenuated H9N2 influenza vaccine is well tolerated and immunogenic in healthy adults. J Infect Dis. 2009 Mar 1;199(5):711-6. doi: 10.1086/596558.

    PubMed 19210163

  • Belshe RB. Current status of live attenuated influenza virus vaccine in the US. Virus Res. 2004 Jul;103(1-2):177-85. doi: 10.1016/j.virusres.2004.02.031.

    PubMed 15163507

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing A/swine/Missouri/4296424/2006 (H2N3) x A/Ann Arbor/6/60 ca (H2N3 MO 2006/AA ca), A/chicken/Hong Kong/G9/97 (H9N2) x A/Ann Arbor/6/60 ca (H9N2 G9/AA ca) and 2012-2013 trivalent seasonal live attenuated influenza vaccine (FluMist®) in people with Influenza, Human, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Dec 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Area under the curve (AUC) of nasal virus shedding after vaccine dose as assessed by liquid titration of nasal secretions on Madin Darby Canine Kidney (MDCK) cells (time frame: Measured through Day 9). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01674205, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Dec 2015.

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