Seasonal Influenza DNA Vaccine & Seasonal Influenza Trivalent Inactivated Vaccine (TIV) in Children & Adolescents
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
1 other identifier
interventional
75
1 country
5
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Jun 2012
5 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 30, 2012
CompletedFirst Posted
Study publicly available on registry
June 1, 2012
CompletedStudy Start
First participant enrolled
June 1, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 1, 2013
CompletedStudy Completion
Last participant's last visit for all outcomes
July 1, 2013
CompletedDecember 6, 2018
December 1, 2018
1.1 years
May 30, 2012
December 4, 2018
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Incidence of solicited and unsolicited adverse events
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.
7 days after injection for solicited events; from 1st injection to study completion for unsolicited events
Mean change from baseline in safety laboratory measures
At day 28 (+/- 7 days) blood will be drawn prior to receiving the second injection to measure hemoglobin, creatinine, and alanine transaminase (ALT).
Day 28
Number of subjects with influenza or influenza-like illnesses
Participants who experience at least one influenza or influenza-like illness will be counted.
Day 0 through 24 weeks post TIV boost (Day 294)
Secondary Outcomes (2)
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.
Week 22 (4 weeks after TIV boost)
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
Week 22 (4 weeks after TIV boost)
Study Arms (6)
Group 1A (12-17yrs):1 mg DNA vaccine+TIV
EXPERIMENTAL2012/13 seasonal influenza DNA Vaccine (VRC-FLUDNA063-00-VP) at Day 0 and licensed 2012/13 TIV at Week 18±2 wks
Group 1B (6-11yrs):1 mg DNA vaccine+TIV
EXPERIMENTAL2012/13 seasonal influenza DNA Vaccine (VRC-FLUDNA063-00-VP) at Day 0 and licensed 2012/13 TIV at Week 18±2 wks
Group 2A (12-17yrs):4 mg DNA vaccine+TIV
EXPERIMENTAL2012/13 seasonal influenza DNA Vaccine (VRC-FLUDNA063-00-VP) at Day 0 and licensed 2012/13 TIV at Week 18±2 wks
Group 2B (6-11yrs):4 mg DNA vaccine+TIV
EXPERIMENTAL2012/13 seasonal influenza DNA Vaccine (VRC-FLUDNA063-00-VP) at Day 0 and licensed 2012/13 TIV at Week 18±2 wks
Group 3A: (12-17yrs): TIV+TIV
ACTIVE COMPARATORLicensed 2012/13 TIV at Day 0 and Week 18±2 wks
Group 3B: (6-11yrs): TIV+TIV
ACTIVE COMPARATORLicensed 2012/13 TIV at Day 0 and Week 18±2 wks
Interventions
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.
2012/13 Seasonal Influenza Trivalent Inactivated Vaccine (TIV)
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (5)
Emory Children's Center
Atlanta, Georgia, 30322, United States
Saint Louis University - Doisy Research Center
St Louis, Missouri, 63104, United States
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, 03756, United States
The Gamble Program for Clinical Studies, Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229, United States
Vanderbilt University
Nashville, Tennessee, 37232, United States
Related Publications (3)
Ledgerwood JE, Wei CJ, Hu Z, Gordon IJ, Enama ME, Hendel CS, McTamney PM, Pearce MB, Yassine HM, Boyington JC, Bailer R, Tumpey TM, Koup RA, Mascola JR, Nabel GJ, Graham BS; VRC 306 Study Team. DNA priming and influenza vaccine immunogenicity: two phase 1 open label randomised clinical trials. Lancet Infect Dis. 2011 Dec;11(12):916-24. doi: 10.1016/S1473-3099(11)70240-7. Epub 2011 Oct 3.
PMID: 21975270BACKGROUNDLedgerwood JE, Graham BS. DNA vaccines: a safe and efficient platform technology for responding to emerging infectious diseases. Hum Vaccin. 2009 Sep;5(9):623-6. doi: 10.4161/hv.8627. No abstract available.
PMID: 19779298BACKGROUNDHouser KV, Yamshchikov GV, Bellamy AR, May J, Enama ME, Sarwar U, Larkin B, Bailer RT, Koup R, Paskel M, Subbarao K, Anderson E, Bernstein DI, Creech B, Keyserling H, Spearman P, Wright PF, Graham BS, Ledgerwood JE; VRC 702 study team. DNA vaccine priming for seasonal influenza vaccine in children and adolescents 6 to 17 years of age: A phase 1 randomized clinical trial. PLoS One. 2018 Nov 2;13(11):e0206837. doi: 10.1371/journal.pone.0206837. eCollection 2018.
PMID: 30388160RESULT
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- 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
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 30, 2012
First Posted
June 1, 2012
Study Start
June 1, 2012
Primary Completion
July 1, 2013
Study Completion
July 1, 2013
Last Updated
December 6, 2018
Record last verified: 2018-12