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

NCT01246999 | Completed Phase 4 Results

• 1 other identifier: URMC10-005/Dartmouth 22164
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 2

Brief 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. Children with a laboratory documented history of prior H1N1 infection will be excluded.

Conditions

Influenza

Keywords

Influenza; A/California/7/2009-like (2009 H1N1); A/Perth/16/2009-like (H3N2); B/Brisbane/60/2008-like (B/Victoria lineage)

Outcome Measures

Primary Outcomes (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.

  baseline to day 7

Secondary Outcomes (6)

• Mean Peak H1N1 Virus Titer, Dose 1

  days 2, 4 and 7

• Mean Peak H3N2 Virus Titer, Dose 1

  days 2, 4 and 7

• Mean Peak Influenza B Virus Titer, Dose 1

  days 2, 4 and 7

• Mean Peak H1N1 Virus Titer, Dose 2

  days 2, 4 and 7

• Mean Peak H3N2 Virus Titer, Dose 2

  days 2, 4 and 7

Study Arms (4)

Live Attenuated Influenza vaccine

ACTIVE COMPARATOR

LAIV 0.2 ml will be given intranasally followed by LAIV 0.2 mg given intranasally 28 days later

Biological: Live attenuated Influenza vaccine

Trivalent Influenza Vaccine 2010-2011

ACTIVE COMPARATOR

TIV 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

Biological: Trivalent Influenza Vaccine

TIV followed by LAIV

ACTIVE COMPARATOR

TIV 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

Biological: TIV followed by LAIV

LAIV followed by TIV

ACTIVE COMPARATOR

LAIV 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

Biological: LAIV followed by TIV

Interventions

Live attenuated Influenza vaccine BIOLOGICAL

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

Also known as: FluMist

Live Attenuated Influenza vaccine

Trivalent Influenza Vaccine BIOLOGICAL

.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.

Also known as: Seasonal Influenza Vaccine

Trivalent Influenza Vaccine 2010-2011

TIV followed by LAIV BIOLOGICAL

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

Also known as: Seasonal Influenza Vaccines

TIV followed by LAIV

LAIV followed by TIV BIOLOGICAL

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

Also known as: Seasonal Influenza Vaccines

LAIV followed by TIV

Eligibility Criteria

• Age: 2 Years - 9 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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.)

You may not qualify if:

• 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).
• 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.

Sponsors & Collaborators

• University of Rochester: lead
• National Institutes of Health (NIH): collaborator
• Dartmouth-Hitchcock Medical Center: collaborator

Study Sites (2)

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

Vaccine Research Unit Room 3-5000

Rochester, New York, 14642, United States

Location

Related Publications (11)

• 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.

  PMID: 19745214 BACKGROUND

• 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.

  PMID: 19423871 BACKGROUND

• 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.

  PMID: 19745216 BACKGROUND

• 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.

  PMID: 17301299 BACKGROUND

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

  PMID: 5773321 BACKGROUND

• 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.

  PMID: 6997969 BACKGROUND

• 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.

  PMID: 10501238 BACKGROUND

• 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.

  PMID: 17050593 BACKGROUND

• 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.

  PMID: 7975853 BACKGROUND

• 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.

  PMID: 16971435 BACKGROUND

• 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.

  PMID: 25165161 DERIVED

MeSH Terms

Conditions

Influenza, Human

Interventions

Influenza Vaccines; FluMist

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Results Point of Contact

• Title: John Treanor MD, Professor of Medicine
• Organization: University of Rochester

John_Treanor@urmc.rochester.edu

585-275-5871

Study Officials

• John J. Treanor, M.D.

  University of Rochester

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D.

Study Record Dates

• First Submitted: November 22, 2010
• First Posted: November 24, 2010
• Study Start: October 1, 2010
• Primary Completion: January 1, 2013
• Study Completion: June 1, 2013
• Last Updated: December 29, 2016
• Results First Posted: October 19, 2016

Record last verified: 2016-11

Locations

US (2)