A/H5N1 Vaccine in Healthy Children Aged 2-9 Years

This study has been completed.
Sponsor:
Information provided by:
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00133536
First received: August 19, 2005
Last updated: August 26, 2010
Last verified: June 2008
  Purpose

The purposes of this study are: to make sure that there are no serious side effects of an experimental inactivated influenza A/H5N1 vaccine in children; and to see how the body's immune system reacts to the vaccine. To look at the side effects, researchers will follow children closely after vaccination. To look at immune system responses, researchers will test the children's blood before and a number of times after vaccination. Participants will include up to 130 healthy children ages 2-9 years. Participants will be assigned to receive 2, up to 3 doses of vaccine, or placebo (inactive substance). Subjects will receive at least 2 doses of vaccine approximately 28 days apart. If data shows an enhanced immune response from a third vaccination, children will be offered a third dose of the vaccine. Participants will be involved in study related procedures for up to 13 months, including up to 6 study visits, plus a number of telephone calls.


Condition Intervention Phase
Influenza
Biological: Influenza A/H5N1 Vaccine
Drug: Placebo
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Prevention
Official Title: A Randomized, Double-Blinded, Placebo-Controlled, Phase I/II, Study of the Safety, Reactogenicity, and Immunogenicity of Intramuscular Inactivated Influenza A/H5N1 Vaccine in Healthy Children Aged 2 Years Through 9 Years

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Adverse event (AE) and serious adverse event (SAE) information (solicited in clinic and via memory aids, concomitant medications, and periodic targeted physical assessments.) [ Time Frame: Solicited AEs-reactogenicity following each vaccination. Unsolicited AEs-SAEs occurring during the length of the study, and nonserious events occurring 28 days after receipt of the 2nd (from enrollment) or 3rd dose of vaccine. ] [ Designated as safety issue: Yes ]
  • Proportion of subjects achieving a serum neutralizing antibody titer of 1:40 against the influenza A/H5N1 virus. [ Time Frame: 28 days after receipt of the 2nd dose of vaccine (Day 56). ] [ Designated as safety issue: No ]
  • Geometric mean titer and the frequency of 4-fold or greater increases in hemagglutination inhibition and neutralizing antibody titers. [ Time Frame: 28 days after receipt of the 2nd dose of vaccine (Day 56). ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Proportion of subjects achieving a serum neutralizing antibody titer of 1:40 against the influenza A/H5N1 virus. [ Time Frame: 1 and 6 months after receipt of first and third doses (if third dose will be administered [see study design]) of vaccine. ] [ Designated as safety issue: No ]
  • Geometric mean titer and the frequency of 4-fold or greater increases in serum hemagglutination inhibition antibody titer. [ Time Frame: 1 and 6 months after receipt of first and third (if third dose will be administered [see study design]) doses of vaccine. ] [ Designated as safety issue: No ]
  • Development of serum antibody responses against antigenically drifted variants of influenza H5N1 virus. [ Time Frame: Blood samples for serum assays will be collected at day 0, approximately 1 month after each immunization, and approximately 6 months after the first immunization and third immunization (if provided). ] [ Designated as safety issue: No ]

Enrollment: 157
Study Start Date: January 2006
Study Completion Date: April 2007
Primary Completion Date: April 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
100 subjects 45 mcg of influenza A/H5N1.
Biological: Influenza A/H5N1 Vaccine
Monovalent inactivated subvirion influenza H5N1 vaccine (derived from A/Vietnam/1203/04). Packaged in single-dose vials of 90 mcg/mL (0.7 mL/vial). Dosage 45 mcg/0.5 mL administered intramuscularly.
Placebo Comparator: 2
20 subjects saline placebo.
Drug: Placebo
Normal saline administered intramuscularly.

Detailed Description:

The goals of this study are to assess the safety, reactogenicity, and immunogenicity of 45-microgram dosage level of monovalent subvirion influenza A/H5N1 virus vaccine administered by intramuscular (IM) route to healthy children. The primary goal of this study is to determine if this dosage level of H5N1 will result in an acceptable proportion of children achieving a potentially protective post vaccination antibody titer (provisionally assigned as a serum neutralizing titer of 1:40, based on studies conducted in Hong Kong during the 1997 H5N1 outbreak). Approximately 130 healthy children, aged 2 through 9 years, will be enrolled in this multicenter, randomized, double-blinded, placebo-controlled, clinical trial to receive at least 2 and up to 3 doses of an inactivated influenza A/H5N1 vaccine at a 45-microgram dose. One hundred subjects will be enrolled and randomly assigned into the influenza A/H5N1 vaccine dose group and 20 subjects into the placebo group (in 5:1 ratio). Subjects will be stratified into 2 age groups (2 to 5 years old and 6 to 9 years old). Vaccine or placebo will be administered into the deltoid. Subjects randomized to receive vaccine will receive 2 doses of the vaccine approximately 28 days apart. At approximately month 5, subjects' parent(s) or guardian(s) will be called to remind them of the 6-month follow-up visit. At the 6-month visit, subjects will be assessed for serious adverse events (SAEs) and the randomization assignment, ie, to vaccine or placebo, will be unmasked to the subject and parent(s) or guardian(s). Should data evaluating a third dose of the influenza A/H5N1 vaccine in adults show enhanced immunogenicity, parents or guardians of subjects who received vaccine will be offered a third dose, with an additional blood draw immediately prior to the third dose and 28 days and 6 months thereafter. The 6-month post-Dose 3 blood draw is optional. For subjects assigned to placebo, the parents or guardians will be offered the opportunity to enroll the subject into a separate open-label protocol if the 2 dose regimen administered to the vaccine recipients is found to be safe and immunogenic. The primary endpoints of the study include: adverse event (AE) and SAE information (solicited in-clinic and via memory aids, concomitant medications, and periodic targeted physical assessments, as indicated); proportion of subjects achieving a serum neutralizing antibody titer of 1:40 against the influenza A/H5N1 virus 28 days after receipt of second dose of vaccine (approximately Day 56); and geometric mean titer (GMT) and the frequency of 4-fold or greater increases in hemagglutination inhibition and neutralizing antibody titers 28 days after receipt of second dose of vaccine (approximately Day 56). The secondary endpoints of the study include: proportion of subjects achieving a serum neutralizing antibody titer of 1:40 against the influenza A/H5N1 virus 1 and 6 months after receipt of first and third doses (if third dose will be administered [see study design]) of vaccine; GMT and the frequency of 4-fold or greater increases in serum hemagglutination inhibition antibody titer 1 and 6 months after receipt of first and third (if third dose will be administered [see study design]) doses of vaccine; and development of serum antibody responses against antigenically drifted variants of influenza H5N1 virus. This study is linked to protocol 06-0072.

  Eligibility

Ages Eligible for Study:   2 Years to 9 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • The subject must be male or female, aged 2 through 9 years at enrollment.
  • The subject must be in good health (and not on any chronic medications), as determined by medical history and a history-directed targeted physical examination.
  • Parents or guardians must be able to understand and comply with planned study procedures and be available for all study visits.
  • Parents or guardians must provide written consent prior to initiation of any study procedures, and subject may provide written assent as appropriate.

Exclusion Criteria:

  • The subject must not have a known allergy to eggs or other components of the vaccine or sensitivity or allergy to latex.
  • The subject must not have a history of asthma or recurrent wheezing.
  • The subject must not be undergoing immunosuppression as a result of an underlying illness or treatment.
  • The subject must not have an active neoplastic disease or a history of any hematologic malignancy.
  • The subject must not be using oral or parenteral steroids, inhaled steroids, or other immunosuppressive or cytotoxic drugs. Note: Subjects on nasal or topical steroids will be allowed to enroll in this study.
  • The subject must not have a history of receiving immunoglobulin or other blood product within the 3 months prior to enrollment in this study.
  • The subject must not have received any other licensed vaccines within 2 weeks (for inactivated vaccines) or 4 weeks (for live vaccines) prior to enrollment in this study.
  • The subject must not have 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, but are not limited to, known chronic liver disease, significant renal disease, unstable or progressive neurological disorders, diabetes mellitus, and transplant recipients).
  • The subject must not have a history of severe reactions following immunization with contemporary influenza virus vaccines.
  • The subject must not have an acute illness, including an axillary temperature greater than 100 degrees F, within 3 days prior to vaccination.
  • The subject must not have received an experimental vaccine or medication within one month prior to enrollment in this study, or expect to receive an experimental vaccine, medication, or blood product during the 13-month study period.
  • The subject must not have any condition that would, in the opinion of the investigator, place them at an unacceptable risk of injury or render the subject unable to meet the requirements of the protocol.
  • History of Guillain-Barré syndrome.
  • The subject must not be participating concurrently in another clinical trial (either in active phase or in follow-up phase).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00133536

Locations
United States, California
UCLA Center For Vaccine Research
Torrance, California, United States, 90502
United States, Maryland
University of Maryland Baltimore
Baltimore, Maryland, United States, 21201
United States, Missouri
Saint Louis University
St. Louis, Missouri, United States, 63104
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229-3039
Sponsors and Collaborators
  More Information

No publications provided

Responsible Party: Robert Johnson, HHS/NIAID/DMID
ClinicalTrials.gov Identifier: NCT00133536     History of Changes
Other Study ID Numbers: 04-077
Study First Received: August 19, 2005
Last Updated: August 26, 2010
Health Authority: United States: Federal Government
United States: Institutional Review Board

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
H5N1, Influenza, children

Additional relevant MeSH terms:
Influenza, Human
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on September 16, 2014