Seasonal Influenza DNA Vaccine & Seasonal Influenza Trivalent Inactivated Vaccine (TIV) in Children & Adolescents

This study has been completed.
Sponsor:
Collaborator:
The EMMES Corporation
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT01609998
First received: May 30, 2012
Last updated: October 15, 2013
Last verified: October 2013
  Purpose

This is a Phase I, dose escalation study in healthy adolescents and children (6-17 years) to evaluate the safety, tolerability, and immunogenicity of a prime-boost regimen of the 2012/2013 seasonal influenza DNA vaccine (HA DNA) followed by licensed 2012/2013 TIV vaccine. The comparator groups will receive licensed 2012/2013 TIV as prime and boost. The hypothesis is that the 2012/2013 HA DNA prime-TIV boost regimen will be safe and result in a broader and more durable immune response than is observed in age-matched comparator TIV-TIV groups.


Condition Intervention Phase
Influenza
Biological: Seasonal Influenza DNA vaccine
Biological: TIV
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Open-Label, Dose-Escalation, Phase I Study of the Prime-Boost Investigational 2012/13 Seasonal Influenza DNA Vaccine, VRC-FLUDNA063-00-VP, Followed by the 2012/2013 Seasonal TIV Compared to TIV Prime-Boost in Children/Adolescents Ages 6-17

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Incidence of solicited and unsolicited adverse events [ Time Frame: 7 days after injection for solicited events; from 1st injection to study completion for unsolicited events ] [ Designated as safety issue: Yes ]
    Incidence is reported for solicited events for 7 days after each injection, for unsolicited adverse event (AE) of any severity for 28 days after each injection, and for serious adverse events or new chronic medical conditions through 24 weeks after the 2nd injection.

  • Mean change from baseline in safety laboratory measures [ Time Frame: Day 28 ] [ Designated as safety issue: Yes ]
    At day 28 (+/- 7 days) blood will be drawn prior to receiving the second injection to measure hemoglobin, creatinine, and alanine transaminase (ALT).

  • Number of subjects with influenza or influenza-like illnesses [ Time Frame: Day 0 through 24 weeks post TIV boost (Day 294) ] [ Designated as safety issue: Yes ]
    Participants who experience at least one influenza or influenza-like illness will be counted.


Secondary Outcome Measures:
  • Proportion of subjects with either a baseline hemagglutination inhibition (HAI) titer <1:10 and post-vaccination HAI titer ≥1:40 or baseline HAI titer ≥1:10 and a minimum 4-fold rise in HAI titer for each of the 3 strains in the 2012/13 TIV at Week 22. [ Time Frame: Week 22 (4 weeks after TIV boost) ] [ Designated as safety issue: No ]
    Blood is collected from all subjects at baseline and at 4 weeks after TIV boost(Week 22 +/- 7 days) for testing in an HAI assay for each of the 3 strains of influenza in the 2012/2013 TIV.

  • Proportion of subjects with a four-fold or greater rise from baseline (Day 0) and Week 22 in 2012/13 TIV specific H1, H3 and B neutralizing antibodies [ Time Frame: Week 22 (4 weeks after TIV boost) ] [ Designated as safety issue: No ]
    Blood is collected from all subjects at baseline (Day 0) and 4 weeks after TIV boost (Week 22 +/- 7 days) for testing in a neutralizing antibody assays for 2012/13 strain-specific H1, H3 and B antigens.


Enrollment: 75
Study Start Date: June 2012
Study Completion Date: July 2013
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1A (12-17yrs):1 mg DNA vaccine+TIV
2012/13 seasonal influenza DNA Vaccine (VRC-FLUDNA063-00-VP) at Day 0 and licensed 2012/13 TIV at Week 18±2 wks
Biological: Seasonal Influenza DNA vaccine
VRC-FLUDNA063-00-VP is composed of 3 closed-circular DNA plasmids that encode for the hemagglutinin (HA) from the following 3 strains: A/California/04/2009 (H1); A/Victoria/361/2011 (H3), and B/Wisconsin/2010. DNA vaccine vials will be supplied at 4 mg/mL in single use vials. The 1 mg dosage is administered as 0.25 mL volume and the 4 mg dosage as a 1 mL volume.
Other Names:
  • VRC-FLUDNA063-00-VP
  • HA DNA Vaccine
  • Seasonal influenza trivalent DNA vaccine
Biological: TIV
2012/13 Seasonal Influenza Trivalent Inactivated Vaccine (TIV)
Other Name: 2012/13 Seasonal Influenza Trivalent Inactivated Vaccine
Experimental: Group 1B (6-11yrs):1 mg DNA vaccine+TIV
2012/13 seasonal influenza DNA Vaccine (VRC-FLUDNA063-00-VP) at Day 0 and licensed 2012/13 TIV at Week 18±2 wks
Biological: Seasonal Influenza DNA vaccine
VRC-FLUDNA063-00-VP is composed of 3 closed-circular DNA plasmids that encode for the hemagglutinin (HA) from the following 3 strains: A/California/04/2009 (H1); A/Victoria/361/2011 (H3), and B/Wisconsin/2010. DNA vaccine vials will be supplied at 4 mg/mL in single use vials. The 1 mg dosage is administered as 0.25 mL volume and the 4 mg dosage as a 1 mL volume.
Other Names:
  • VRC-FLUDNA063-00-VP
  • HA DNA Vaccine
  • Seasonal influenza trivalent DNA vaccine
Biological: TIV
2012/13 Seasonal Influenza Trivalent Inactivated Vaccine (TIV)
Other Name: 2012/13 Seasonal Influenza Trivalent Inactivated Vaccine
Experimental: Group 2A (12-17yrs):4 mg DNA vaccine+TIV
2012/13 seasonal influenza DNA Vaccine (VRC-FLUDNA063-00-VP) at Day 0 and licensed 2012/13 TIV at Week 18±2 wks
Biological: Seasonal Influenza DNA vaccine
VRC-FLUDNA063-00-VP is composed of 3 closed-circular DNA plasmids that encode for the hemagglutinin (HA) from the following 3 strains: A/California/04/2009 (H1); A/Victoria/361/2011 (H3), and B/Wisconsin/2010. DNA vaccine vials will be supplied at 4 mg/mL in single use vials. The 1 mg dosage is administered as 0.25 mL volume and the 4 mg dosage as a 1 mL volume.
Other Names:
  • VRC-FLUDNA063-00-VP
  • HA DNA Vaccine
  • Seasonal influenza trivalent DNA vaccine
Biological: TIV
2012/13 Seasonal Influenza Trivalent Inactivated Vaccine (TIV)
Other Name: 2012/13 Seasonal Influenza Trivalent Inactivated Vaccine
Experimental: Group 2B (6-11yrs):4 mg DNA vaccine+TIV
2012/13 seasonal influenza DNA Vaccine (VRC-FLUDNA063-00-VP) at Day 0 and licensed 2012/13 TIV at Week 18±2 wks
Biological: Seasonal Influenza DNA vaccine
VRC-FLUDNA063-00-VP is composed of 3 closed-circular DNA plasmids that encode for the hemagglutinin (HA) from the following 3 strains: A/California/04/2009 (H1); A/Victoria/361/2011 (H3), and B/Wisconsin/2010. DNA vaccine vials will be supplied at 4 mg/mL in single use vials. The 1 mg dosage is administered as 0.25 mL volume and the 4 mg dosage as a 1 mL volume.
Other Names:
  • VRC-FLUDNA063-00-VP
  • HA DNA Vaccine
  • Seasonal influenza trivalent DNA vaccine
Biological: TIV
2012/13 Seasonal Influenza Trivalent Inactivated Vaccine (TIV)
Other Name: 2012/13 Seasonal Influenza Trivalent Inactivated Vaccine
Active Comparator: Group 3A: (12-17yrs): TIV+TIV
Licensed 2012/13 TIV at Day 0 and Week 18±2 wks
Biological: TIV
2012/13 Seasonal Influenza Trivalent Inactivated Vaccine (TIV)
Other Name: 2012/13 Seasonal Influenza Trivalent Inactivated Vaccine
Active Comparator: Group 3B: (6-11yrs): TIV+TIV
Licensed 2012/13 TIV at Day 0 and Week 18±2 wks
Biological: TIV
2012/13 Seasonal Influenza Trivalent Inactivated Vaccine (TIV)
Other Name: 2012/13 Seasonal Influenza Trivalent Inactivated Vaccine

Detailed Description:

Vaccines are an effective way to prevent influenza infection. Each year the World Health Organization (WHO) and the U.S FDA recommend the influenza strains to include in the seasonal influenza vaccines. The licensed seasonal influenza vaccines are directed against 3 influenza virus strains: an influenza A H1N1, an influenza A H3N2, and an influenza B. The currently approved vaccines depend upon labor-intensive methods that limit manufacturing speed and capacity. Influenza vaccines that can be more rapidly produced and that induce stronger, broader and more persistent immune responses are a recognized public health need.

In this protocol we will evaluate an investigational seasonal influenza (HA DNA) vaccine in healthy adolescents and children (6-17 years). Some participants will receive HA DNA vaccine "prime" followed by licensed trivalent influenza vaccine (TIV) "boost" 18 weeks later. Other participants will receive two TIV injections 18 weeks apart. The results will be compared. The HA DNA vaccine and TIV are both directed at the 3 influenza strains selected for the 2012/2013 vaccines. Prior studies in adults of avian and seasonal influenza DNA vaccines have been completed. The DNA vaccinations were assessed as safe and well tolerated in adults. The immune response to avian influenza is augmented by DNA vaccine priming compared to two vaccinations with the inactivated avian influenza (H5N1)vaccine when the prime-boost interval is 12-24 weeks, but not when the prime-boost interval is 4 weeks.

  Eligibility

Ages Eligible for Study:   6 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Children/adolescents aged 6 to 17 years inclusive and at least 20 kg in weight.
  • Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process.
  • Willing to have blood drawn 5 times over 42 weeks, including blood stored for research purposes.
  • In good general health as assessed by medical history, vital signs and targeted physical examination; stable medical conditions that, in the opinion of the investigator, will not compromise the subject's participation in the study are acceptable.
  • Capability of the legal adult representative of the minor to understand and comply with planned study procedures.
  • Capability of the legal adult representative of the minor to provide written informed consent; assent will be obtained from the child/adolescent per requirements of the site institutional review board (IRB).
  • For female adolescent of child-bearing potential (as defined by onset of menses): agrees to avoid becoming pregnant and to use effective method of contraception or practice abstinence for at least 21 day prior to the first study vaccine administration, until at least 4 weeks after the second study vaccination.
  • Within 70 days prior to enrollment, hemoglobin within institutional normal limits, creatinine less than the upper limit of normal (ULN) and ALT ≤1.5 X ULN for respective age group.

Exclusion Criteria:

  • History of Guillain-Barré syndrome.
  • Active neoplasm or history of cancer.
  • On-going immunosuppressive therapy or known to be immunosuppressed at the time of enrollment.
  • Immunoglobulin (or similar blood product) therapy within 3 months prior to enrollment.
  • Known to have HIV, hepatitis B or hepatitis C infection.
  • Acute or chronic illness that, in the opinion of the investigator, precludes participation in the study.
  • Developmental delay, neurologic disorder, or seizure disorder requiring ongoing medical management (note: history of febrile seizure is not an exclusion).
  • Acute febrile and/or respiratory illness within one week prior to enrollment.
  • Idiopathic urticaria within the year prior to enrollment.
  • Allergy treatment with antigen injections, unless on maintenance schedule and allergy shots could be staggered with the study vaccinations, within 14 days (2 weeks) prior to enrollment.
  • Asthma that is severe, unstable or required emergent care, urgent care, hospitalization or intubation during the previous two years or that is expected to require the use of oral, intravenous or high dose inhaled corticosteroids.
  • Vaccination of any type within 2 weeks prior to enrollment or receipt of the 2012/2013 seasonal TIV any time prior to enrollment.
  • Participating in or planning to begin participation in another investigational study during the projected time during which the subject would be in this study.
  • Factors related to the legal representative that in the judgment of the investigator may affect the objective decision-making of the legal representative.
  • For a female adolescent of child-bearing potential: breast-feeding, known pregnancy or positive urine or serum pregnancy test on day of study enrollment.
  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: NCT01609998

Locations
United States, Georgia
Emory Children's Center
Atlanta, Georgia, United States, 30322
United States, Missouri
Saint Louis University - Doisy Research Center
St. Louis, Missouri, United States, 63104
United States, New Hampshire
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03756
United States, Ohio
The Gamble Program for Clinical Studies, Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
United States, Tennessee
Vanderbilt University
Nashville, Tennessee, United States, 37232
Sponsors and Collaborators
The EMMES Corporation
Investigators
Study Director: Barney Graham, S Graham, M.D., Ph.D. Chief, Clinical Trials Core Vaccine Research Center, NIAID, NIH
Study Chair: Julie Ledgerwood, D.O. Deputy Chief, Clinical Trials Core Vaccine Research Center, NIAID, NIH
  More Information

Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT01609998     History of Changes
Other Study ID Numbers: VRC 702, VRC 702
Study First Received: May 30, 2012
Last Updated: October 15, 2013
Health Authority: United States: Federal Government
United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Influenza A (H1)
Influenza A (H3)
Influenza B
DNA Vaccine
Trivalent Inactivated Vaccine (TIV)
Healthy Adolescents
Healthy 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 30, 2014