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InfluenzaPhase 4NCT01246999

Effect of Age and Prior Immunity to Response to Seasonal Influenza Vaccines in Children

A Phase 4 study testing Live attenuated Influenza vaccine, Trivalent Influenza Vaccine and TIV followed by LAIV in people with Influenza, run by University of Rochester at 2 sites 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

A total of 88 children between 2 and 9 years of age will be randomized to receive a two dose schedule of either licensed live attenuated trivalent seasonal influenza vaccine (LAIV) or licensed inactivated seasonal influenza vaccine (TIV)or TIV followed by LAIV or LAIV followed by TIV separated by 28 days. Read more about this study

Who is it for?
Ages 2 to 9 yearsHealthy volunteers can take part
Conditions the study is for
Influenza
What is being tested?
Live attenuated Influenza vaccine, Trivalent Influenza Vaccine and TIV followed by LAIV
Could I receive a placebo?
No, everyone receives an active treatment
How many people
34 participants
Where
2 sitesUnited States
Study dates
Oct 2010to Jun 2013
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 2 to 9 years
  • All sexes
  • Healthy volunteers accepted
  • Child

Who may be able to join

  • Aged between 2 and 9 years, inclusive.
  • No prior history of laboratory documented infection with novel H1N1 virus
  • The subject must be in good health, as determined by: vital signs (heart rate <140 bpm; blood pressure: systolic ≥ 90 mm Hg and ≤140 mm Hg; diastolic ≤ 90 mm Hg; oral temperature <100.0ºF (fahrenheit); medical history; and targeted physical examination, when necessary, based on medical history. Stable medical condition is defined as: no recent increase in prescription medication, dose, or frequency of medication in the last 3 months and health outcomes of the specific disease are considered to be within acceptable limits in the last 6 months.
  • The subject/parents are able to understand and comply with the planned study procedures, including being available for all study visits.
  • The subject/parents have provided informed consent prior to any study procedures. (An assent will be obtained for all children as required by the institutional IRB (Institutional Review Board.)

Who cannot join

  • Subjects with a laboratory documented history of previous novel H1N1 infection.
  • History of egg allergy or allergy to other components of vaccine.
  • History of wheezing.
  • The subject is immunosuppressed as a result of an underlying illness or treatment with immunosuppressive or cytotoxic drugs, or use of anticancer chemotherapy or radiation therapy.
  • The subject has an active neoplastic disease.
  • The subject has long-term (greater than 2 weeks) use of oral or parenteral steroids, or high-dose inhaled steroids (>800 mg/day of beclomethasone dipropionate or equivalent) within the preceding 6 months (nasal and topical steroids are allowed).
Show all 15Show fewer
  • The subject received immunoglobulin or another blood product within the 3 months prior to enrollment in this study.
  • The subject has received an inactivated vaccine within the 2 weeks or a live vaccine within the 4 weeks prior to enrollment in this study or plans to receive another vaccine within the next 28 days (or 56 days for vaccine naïve recipients).
  • The subject has an acute or chronic medical condition that, in the opinion of the investigator, would render vaccination unsafe or would interfere with the evaluation of responses. These conditions include chronic conditions recognized as risk factors for influenza complications or as contraindications for live vaccination, including chronic cardiac (exclusive of hypertension) or pulmonary conditions (including asthma), diabetes mellitus, or renal impairment.
  • The subject has an acute illness or an oral temperature greater than 99.9 degreesF (37.7 degrees C) within 3 days prior to enrollment or vaccination. Subjects who had an acute illness that was treated symptoms resolved are eligible to enroll as long as treatment is completed and symptoms resolve > 3 days prior to enrollment.
  • The subject is currently participating or plans to participate in a study that involves an experimental agent (vaccine, drug, biologic, device, blood product, or medication) or has received an experimental agent within 1 month prior to enrollment in this study, or expects to receive another experimental agent during participation in this study, or intends to donate blood during the study period.
  • The subject has any condition that would, in the opinion of the site investigator, place the subject at an unacceptable risk of injury or render the subject unable to meet the requirements of the protocol.
  • The subject has a known human immunodeficiency virus, hepatitis B, or hepatitis C infection.
  • The subject has a previous history of Guillain-Barré syndrome within 6 weeks of receipt of influenza vaccination.
  • The subject has any condition that the principal investigator (PI) believes may interfere with successful completion of the study.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Dartmouth-Hitchcock Medical Center

    Lebanon, New Hampshire, 03756

  • Vaccine Research Unit Room 3-5000

    Rochester, New York, 14642

Other trials in United States

About this study

Official title: Evaluation of the Effect of Age and Prior Immunity on the Response to Live or Inactivated Seasonal (A/California/7/2009-like, A/Perth/16/2009-like, and B/Brisbane/60/2008-like (B/Victoria Lineage) Influenza Vaccines in Children

A total of 88 children between 2 and 9 years of age will be randomized to receive a two dose schedule of either licensed live attenuated trivalent seasonal influenza vaccine (LAIV) or licensed inactivated seasonal influenza vaccine (TIV)or TIV followed by LAIV or LAIV followed by TIV separated by 28 days. Children with a laboratory documented history of prior H1N1 infection will be excluded.

Read the detailed description

The study will be conducted as a randomized, prospective, open-label evaluation of the clinical tolerability, vaccine virus shedding, and serum and mucosal antibody response to vaccination with either live trivalent influenza vaccine (LAIV) or trivalent influenza vaccine (TIV) in healthy children between the ages of 2 and 9 years. Children will be screened for antibody to A/Brisbane/57/07 (H1N1) and A/California/07/09 (H1N1), A/Perth/16/2009 (H3N2) and B/Brisbane/60/2008 before and at indicated times after the start of the study. They will not be randomized based on antibody levels. Children with prior documented infection with the 2009 pandemic H1N1 virus will be excluded. Vaccine will be administered on days 0 and 28.

Safety of vaccination will be assessed using symptoms collected by parents for 7 days after each dose of vaccine. Serum will be obtained prior to and on day 28 following each dose of vaccine and assessed for antibody by HAI, ELISA, and neutralization techniques. Nasal secretions will be obtained by nasal wick prior to and on day 28 after each dose and assessed for HA-specific IgA (immune globulin A) and IgG (immune globulin G)antibody by ELISA. Nasal swabs will be obtained on days 2, 4, and 7 after each dose of live vaccine and assessed for the presence and magnitude of vaccine virus shedding of the live attenuated vaccine by rtRT-PCR (real-time reverse transcriptase polymerase chain reaction)and TCID50 (50% tissue culture infectious doses)on MDCK(Madin Darby Canine Kidney) cells.

Conditions
Influenza
Being tested
Live attenuated Influenza vaccine, Trivalent Influenza Vaccine, TIV followed by LAIV, LAIV followed by TIV
Keywords
Influenza, A/California/7/2009-like (2009 H1N1), A/Perth/16/2009-like (H3N2), B/Brisbane/60/2008-like (B/Victoria lineage)
Medical subject headings
Influenza, Human

What participants receive

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

  • Live attenuated Influenza vaccineBiological

    Also called FluMist

    0.2 mL dose delivered through nasal spray, 0.1 ml in each nostril, 2 doses separated by 28 days

  • Trivalent Influenza VaccineBiological

    Also called Seasonal Influenza Vaccine

    .25 mL given intramuscularly to children 24 to 36 months of age, 2 doses given 28 days apart, .5 mL given intramuscularly to children 37 months to 9 years of age, 2 doses given 28 day s apart.

  • TIV followed by LAIVBiological

    Also called Seasonal Influenza Vaccines

    TIV .25 mL given intramuscularly to children 24 to 36 months of age or .5 mL given intramuscularly to children 37 months to 9 years of age, followed by FluMist 0.2 mL delivered by nasal spray (.1 mL in each nostril)28 days later

  • LAIV followed by TIVBiological

    Also called Seasonal Influenza Vaccines

    LAIV .2 mL given through nasal spray (.1 mL in each nostril) Followed by TIV .25 mL given intramuscularly to children 24 to 25 months of age or .5 mL given intramuscularly to children 36 months to 9 years of age 28 days later

Study groups in NCT01246999
Study groupRoleWhat they receive
Live Attenuated Influenza vaccineActive comparatorLAIV 0.2 ml will be given intranasally followed by LAIV 0.2 mg given intranasally 28 days later
Receives: Biological: Live attenuated Influenza vaccine
Trivalent Influenza Vaccine 2010-2011Active comparatorTIV will be given in a dose of .25mg 2 years to 36 months of age or .5 ml ages 37 months to 8 years intramuscularly followed by a second dose of .25mg 2 years to 36 months of age or .5 ml ages 37 months to 9 years intramuscularly 28 days later
Receives: Biological: Trivalent Influenza Vaccine
TIV followed by LAIVActive comparatorTIV will be given in a dose of .25mg 2 years to 36 months of age or .5 ml ages 37 months to 9 years intramuscularly followed by LAIV given in a dose of .2 ml intranasally 28 days later
Receives: Biological: TIV followed by LAIV
LAIV followed by TIVActive comparatorLAIV will be given in a dose of .2 ml intranasally followed by a dose of TIV given in a dose of .25 ml 2 years to 36 months or .5 ml 37 months to 9 years intramuscularly 28 days later
Receives: Biological: LAIV followed by TIV

What is being measured

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

  1. Number of Subjects Shedding Vaccine Virus of Each Subtype by PCR

    Nasal washes were collected on days 2, 4 and 7 after vaccination. Nasal swab specimens were tested for the presence of vaccine viruses by quantitative viral culture in MDCK cells at 33º C and by real-time quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) amplification. The limit of detection of vaccine viruses was 10^0.6 tissue culture infectious doses (50%)/ml for virus culture and 10^0.4 tissue culture infectious doses (50%)/ml for qRT-PCR.

    Measured: baseline to day 7

Secondary outcomes (6)

  1. Mean Peak H1N1 Virus Titer, Dose 1

    After the first dose of vaccine, the virus titer from nasal secretions was measured in tissue culture on days 2, 4 and 7 and the highest titer from one of those three time points was reported.

    Measured: days 2, 4 and 7

  2. Mean Peak H3N2 Virus Titer, Dose 1

    After the first dose of vaccine, the virus titer from nasal secretions was measured in tissue culture on days 2, 4 and 7 and the highest titer from one of those three time points was reported.

    Measured: days 2, 4 and 7

  3. Mean Peak Influenza B Virus Titer, Dose 1

    After the first dose of vaccine, the virus titer from nasal secretions was measured in tissue culture on days 2, 4 and 7 and the highest titer from one of those three time points was reported.

    Measured: days 2, 4 and 7

  4. Mean Peak H1N1 Virus Titer, Dose 2

    After the second dose of vaccine, the virus titer from nasal secretions was measured in tissue culture on days 2, 4 and 7 and the highest titer from one of those three time points was reported.

    Measured: days 2, 4 and 7

  5. Mean Peak H3N2 Virus Titer, Dose 2

    After the second dose of vaccine, the virus titer from nasal secretions was measured in tissue culture on days 2, 4 and 7 and the highest titer from one of those three time points was reported.

    Measured: days 2, 4 and 7

  6. Mean Peak Influenza B Virus Titer, Dose 2

    After the second dose of vaccine, the virus titer from nasal secretions was measured in tissue culture on days 2, 4 and 7 and the highest titer from one of those three time points was reported.

    Measured: days 2, 4 and 7

Timeline

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

  1. First posted24 Nov 2010 (estimated)
  2. Study startOct 2010
  3. Primary completionJan 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 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
34 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01246999
Sponsor's protocol ID
URMC10-005/Dartmouth 22164
Status last verified
Nov 2016
First submitted
22 Nov 2010
Last updated
29 Dec 2016
Data monitoring committee
No

Publications

  • Hancock K, Veguilla V, Lu X, Zhong W, Butler EN, Sun H, Liu F, Dong L, DeVos JR, Gargiullo PM, Brammer TL, Cox NJ, Tumpey TM, Katz JM. Cross-reactive antibody responses to the 2009 pandemic H1N1 influenza virus. N Engl J Med. 2009 Nov 12;361(20):1945-52. doi: 10.1056/NEJMoa0906453. Epub 2009 Sep 10.

    PubMed 19745214

  • Shinde V, Bridges CB, Uyeki TM, Shu B, Balish A, Xu X, Lindstrom S, Gubareva LV, Deyde V, Garten RJ, Harris M, Gerber S, Vagasky S, Smith F, Pascoe N, Martin K, Dufficy D, Ritger K, Conover C, Quinlisk P, Klimov A, Bresee JS, Finelli L. Triple-reassortant swine influenza A (H1) in humans in the United States, 2005-2009. N Engl J Med. 2009 Jun 18;360(25):2616-25. doi: 10.1056/NEJMoa0903812. Epub 2009 May 7.

    PubMed 19423871

  • Greenberg ME, Lai MH, Hartel GF, Wichems CH, Gittleson C, Bennet J, Dawson G, Hu W, Leggio C, Washington D, Basser RL. Response to a monovalent 2009 influenza A (H1N1) vaccine. N Engl J Med. 2009 Dec 17;361(25):2405-13. doi: 10.1056/NEJMoa0907413. Epub 2009 Sep 10.

    PubMed 19745216

  • Belshe RB, Edwards KM, Vesikari T, Black SV, Walker RE, Hultquist M, Kemble G, Connor EM; CAIV-T Comparative Efficacy Study Group. Live attenuated versus inactivated influenza vaccine in infants and young children. N Engl J Med. 2007 Feb 15;356(7):685-96. doi: 10.1056/NEJMoa065368.

    PubMed 17301299

  • Maassab HF. Biologic and immunologic characteristics of cold-adapted influenza virus. J Immunol. 1969 Mar;102(3):728-32. No abstract available.

    PubMed 5773321

  • Chanock RM, Murphy BR. Use of temperature-sensitive and cold-adapted mutant viruses in immunoprophylaxis of acute respiratory tract disease. Rev Infect Dis. 1980 May-Jun;2(3):421-32. doi: 10.1093/clinids/2.3.421.

    PubMed 6997969

  • Boyce TG, Gruber WC, Coleman-Dockery SD, Sannella EC, Reed GW, Wolff M, Wright PF. Mucosal immune response to trivalent live attenuated intranasal influenza vaccine in children. Vaccine. 1999 Aug 20;18(1-2):82-8. doi: 10.1016/s0264-410x(99)00183-8.

    PubMed 10501238

  • Sasaki S, Jaimes MC, Holmes TH, Dekker CL, Mahmood K, Kemble GW, Arvin AM, Greenberg HB. Comparison of the influenza virus-specific effector and memory B-cell responses to immunization of children and adults with live attenuated or inactivated influenza virus vaccines. J Virol. 2007 Jan;81(1):215-28. doi: 10.1128/JVI.01957-06. Epub 2006 Oct 18.

    PubMed 17050593

  • Cox RJ, Brokstad KA, Zuckerman MA, Wood JM, Haaheim LR, Oxford JS. An early humoral immune response in peripheral blood following parenteral inactivated influenza vaccination. Vaccine. 1994 Aug;12(11):993-9. doi: 10.1016/0264-410x(94)90334-4.

    PubMed 7975853

  • He XS, Holmes TH, Zhang C, Mahmood K, Kemble GW, Lewis DB, Dekker CL, Greenberg HB, Arvin AM. Cellular immune responses in children and adults receiving inactivated or live attenuated influenza vaccines. J Virol. 2006 Dec;80(23):11756-66. doi: 10.1128/JVI.01460-06. Epub 2006 Sep 13.

    PubMed 16971435

  • Ilyushina NA, Haynes BC, Hoen AG, Khalenkov AM, Housman ML, Brown EP, Ackerman ME, Treanor JJ, Luke CJ, Subbarao K, Wright PF. Live attenuated and inactivated influenza vaccines in children. J Infect Dis. 2015 Feb 1;211(3):352-60. doi: 10.1093/infdis/jiu458. Epub 2014 Aug 26.

    PubMed 25165161

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Live attenuated Influenza vaccine, Trivalent Influenza Vaccine and TIV followed by LAIV in people with Influenza, run by University of Rochester at 2 sites 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 15 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 29 Dec 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites 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. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Oct 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Number of Subjects Shedding Vaccine Virus of Each Subtype by PCR (time frame: baseline to day 7). 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 NCT01246999, which also lists 11 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 29 Dec 2016.

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