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

Influenza Clinical Trial

Official title:

Evaluation of the Effect of Age and Prior Immunity on the Response to Live or Inactivated Seasonal (A/California/7/2009-like (2009 H1N1), A/Perth/16/2009-like (H3N2), and B/Brisbane/60/2008-like (B/Victoria Lineage) Influenza Vaccines in Children

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01246999
• Other study ID #: URMC10-005/Dartmouth 22164
• Status: Active, not recruiting
• Phase: Phase 4
• First received: November 22, 2010
• Last updated: August 2, 2011
• Start date: October 2010
• Est. completion date: April 2012

Study information

• Verified date: November 2010
• Source: University of Rochester
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

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

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 and IgG 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 and TCID50 on MDCK cells.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 88
• Est. completion date: April 2012
• Est. primary completion date: April 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 2 Years to 9 Years

Eligibility

Inclusion Criteria:

• 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); 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.)

Exclusion Criteria:

• 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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Influenza
• Influenza, Human

Intervention

Biological:
• Trivalent Seasonal Live attenuated Influenza vaccine
0.2 mL dose delivered through nasal spray, 0.1 ml in each nostril, 2 doses separated by 28 days
• Seasonal Trivalent Influenza Vaccine 2010-2011
.25 mL given intramuscularly to children 24 to 25 months of age, 2 doses given 28 days apart, .5 mL given intramuscularly to children 36 months to 9 years of age, 2 doses given 28 day s apart.
• Seasonal Influenza Vaccine TIV/LAIV
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, followed by FluMist 0.2 mL delivered by nasal spray (.1 mL in each nostril)28 days later
• Seasonal Influenza Vaccines LAIV/TIV
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

Locations

Country	Name	City	State
United States	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	Vaccine Research Unit Room 3-5000	Rochester	New York

Sponsors (3)

Lead Sponsor	Collaborator
University of Rochester	Dartmouth-Hitchcock Medical Center, National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

References & Publications (10)

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. Erratum in: N Engl J Med. 2007 Mar 22;356(12):1283. — View Citation

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. — View Citation

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. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. Epub 2006 Sep 13. — View Citation

Maassab HF. Biologic and immunologic characteristics of cold-adapted influenza virus. J Immunol. 1969 Mar;102(3):728-32. — View Citation

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. Epub 2006 Oct 18. — View Citation

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. Erratum in: N Engl J Med. 2009 Jul 2;361(1):102. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary end point for assessment of live attenuated vaccine take will be the AUC of nasopharyngeal strain-specific virus assessed by immunoperoxidase stained plaquesin MDCK cells at 33 degrees C		nasal swabs obtained at day 2 post vacination	No
Primary	The primary end point for assessment of live attenuated vaccine take will be the AUC of nasopharyngeal strain-specific virus assessed by immunoperoxidase stained plaquesin MDCK cells at 33 degrees C		nasal swab at day 4 post vaccination	No
Primary	The primary end point for assessment of live attenuated vaccine take will be the AUC of nasopharyngeal strain-specific virus assessed by immunoperoxidase stained plaquesin MDCK cells at 33 degrees C		nasal swab obtained at 7 days post vaccination	No
Secondary	The AUC of live vaccine shedding determined by quantitative rtRT-PCR		nasal swab on day 2 post vaccination	No
Secondary	The frequency and magnitude of hemagglutinin-inhibition (HAI) IgG and IgA ELISA, and neutralizing antibody response to vaccine		at day 28	No
Secondary	The frequency and magnitude of hemagglutinin-specific mucosal IgG and IgA responses assessed by ELISA on nasal secretions		day 28	No
Secondary	Development of specific local and systemic symptoms occurring after vaccine		for 7 days post each vaccination	Yes
Secondary	The frequency and magnitude of hemagglutinin-inhibition (HAI) IgG and IgA ELISA, and neutralizing antibody response to vaccine		day 56	No
Secondary	The frequency and magnitude of hemagglutinin-specific mucosal IgG and IgA responses assessed by ELISA on nasal secretions		day 56	No