An Open-Label, Randomized Phase I Study in Healthy Adults of the Safety and Immunogenicity of Prime-Boost Intervals With Monovalent Influenza Subunit Virion (H5N1) Vaccine, A/Indonesia/05/2005 (Sanofi Pasteur, Inc.) Administered Alone or Following Re...
VRC 310: An Open-Label, Randomized Ph I: Healthy Adults of Prime-Boost Intervals w/Monovalent Influenza Virion (H5N1) Vaccine, A/Indonesia/05/2005 (Sanofi Pasteur, Inc), Administered Alone or Following Recombinant H5 DNA Vaccine
2 other identifiers
interventional
64
1 country
1
Brief Summary
Background: \- New vaccines against avian influenza, also known as "bird flu," are being developed and require testing to determine if they are safe and effective and whether they have any side effects. Researchers are interested in testing two experimental avian influenza vaccines to see whether they are safe, if there are any side effects from the vaccines, and how the body's immune response differs in response to different vaccination schedules. One vaccine is an inactivated vaccine (made with killed or weakened influenza) and one is a DNA vaccine that allows the body to use vaccine to make an immune system response to a specific part of an avian influenza protein. Objectives:
- To determine the safety and potential side effects of two experimental vaccines against avian influenza.
- To evaluate whether the time between the two experimental vaccine injections affects the immune response to the vaccine. Eligibility: \- Healthy individuals between 18 and 60 years of age. Design:
- Participants will be randomly divided (by chance) into six groups to receive two injections of vaccine at different intervals. One group will receive only the inactivated vaccine, while the other groups will receive the DNA vaccine followed by the inactivated vaccine at different intervals (e.g., 4 weeks, 8 weeks, 12 weeks, 16 weeks or 24 weeks later).
- Participants will remain at the clinical center for at least 30 minutes after each vaccination. A few days after each injection, participants will contact staff by telephone or have a clinic visit. Participants will also be asked to complete a diary card at home for 5 days to keep track of temperature changes, injection site skin changes, and other effects.
- Four weeks after the first injection, participants will return for a clinic visit and to provide blood samples for testing.
- Two weeks after the second injection, participants will return for a clinic visit and provide blood samples (collected through apheresis) to provide information on immune response to the vaccine.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Feb 2010
1 active site
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
Study Start
First participant enrolled
February 25, 2010
CompletedFirst Submitted
Initial submission to the registry
March 12, 2010
CompletedFirst Posted
Study publicly available on registry
March 15, 2010
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 12, 2011
CompletedStudy Completion
Last participant's last visit for all outcomes
December 12, 2011
CompletedJuly 2, 2017
December 12, 2011
1.8 years
March 12, 2010
June 30, 2017
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Safety: adverse events, including clinical, laboratory and local and systemic reactogenicity
Secondary Outcomes (1)
Immunogenicity as measured by humoral and cellular assays.
Study Arms (6)
Group 1
EXPERIMENTALInactivated H5N1 Vaccine at Enrollment and inactivated H5N1 Vaccine at Week 24
Group 2
EXPERIMENTALH5 DNA Vaccine at Enrollment and Inactivated H5N1 Vaccine at Week 4
Group 3
EXPERIMENTALH5 DNA Vaccine at Enrollment and Inactivated H5N1 Vaccine at Week 8
Group 4
EXPERIMENTALH5 DNA Vaccine at Enrollment and Inactivated H5N1 Vaccine at Week 12
Group 5
EXPERIMENTALH5 DNA Vaccine at Enrollment and Inactivated H5N1 Vaccine at Week 16
Group 6
EXPERIMENTALH5 DNA Vaccine at Enrollment and Inactivated H5N1 Vaccine at Week 24
Interventions
Eligibility Criteria
You may qualify if:
- A subject must meet all of the following criteria:
- to 60 years old.
- Available for clinical follow-up for up to 32 weeks after enrollment.
- Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process.
- Complete an Assessment of Understanding (AoU) questionnaire prior to enrollment and verbalize understanding of all questions answered incorrectly.
- Able and willing to complete the informed consent process.
- Willing to donate blood for sample storage to be used for future research.
- In good general health without clinically significant medical history.
- Physical examination and laboratory results without clinically significant findings and a Body Mass Index (BMI) \< 40 within the 56 days prior to enrollment.
- Laboratory Criteria within 56 days prior to enrollment:
- Hemoglobin greater than or equal to 11.5 g/dL for women; greater than or equal to13.5 g/dL for men
- White blood cells (WBC) = 3,300-12,000 cells/mm(3)
- Differential either within institutional normal range or accompanied by site physician approval
- Total lymphocyte count greater than or equal to 800 cells/mm3
- Platelets = 125,000 - 500,000/mm(3)
- +14 more criteria
You may not qualify if:
- A subject will be excluded if one or more of the following conditions apply.
- Women Specific:
- Breast-feeding or planning to become pregnant during the first 28 weeks after enrollment in the study.
- Subject has received any of the following substances:
- Systemic immunosuppressive medications or cytotoxic medications within the 12 weeks prior to enrollment. \[With the exception that a short course (duration of 10 days or less or a single injection) of corticosteroids for a self-limited condition at least 2 weeks prior to enrollment in this study will not exclude study participation.\]
- Blood products within 112 days (16 weeks) prior to HIV screening
- Immunoglobulin within 56 days (8 weeks) prior to HIV screening
- Live attenuated vaccines within 28 days (4 weeks) prior to initial study vaccine administration
- Investigational research agents within 28 days (4 weeks) prior to initial study vaccine administration
- Medically indicated subunit or killed vaccines, e.g. influenza, pneumococcal, or allergy treatment with antigen injections, within 14 days (2 weeks) of initial study vaccine administration
- Current anti-TB prophylaxis or therapy
- Previous H5 avian influenza investigational vaccine.
- Subject has a history of any of the following clinically significant conditions:
- Contraindication to receiving an FDA approved current seasonal influenza vaccination (e.g., egg allergy)
- Serious reactions to vaccines that preclude receipt of study vaccinations as determined by the investigator.
- +14 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892, United States
Related Publications (7)
Subbarao K, Murphy BR, Fauci AS. Development of effective vaccines against pandemic influenza. Immunity. 2006 Jan;24(1):5-9. doi: 10.1016/j.immuni.2005.12.005.
PMID: 16413916BACKGROUNDLuke CJ, Subbarao K. Vaccines for pandemic influenza. Emerg Infect Dis. 2006 Jan;12(1):66-72. doi: 10.3201/eid1201.051147.
PMID: 16494720BACKGROUNDTaubenberger JK, Reid AH, Lourens RM, Wang R, Jin G, Fanning TG. Characterization of the 1918 influenza virus polymerase genes. Nature. 2005 Oct 6;437(7060):889-93. doi: 10.1038/nature04230.
PMID: 16208372BACKGROUNDAndrews SF, Raab JE, Gorman J, Gillespie RA, Cheung CSF, Rawi R, Cominsky LY, Boyington JC, Creanga A, Shen CH, Harris DR, Olia AS, Nazzari AF, Zhou T, Houser KV, Chen GL, Mascola JR, Graham BS, Kanekiyo M, Ledgerwood JE, Kwong PD, McDermott AB. A single residue in influenza virus H2 hemagglutinin enhances the breadth of the B cell response elicited by H2 vaccination. Nat Med. 2022 Feb;28(2):373-382. doi: 10.1038/s41591-021-01636-8. Epub 2022 Feb 3.
PMID: 35115707DERIVEDLedgerwood JE, Zephir K, Hu Z, Wei CJ, Chang L, Enama ME, Hendel CS, Sitar S, Bailer RT, Koup RA, Mascola JR, Nabel GJ, Graham BS; VRC 310 Study Team. Prime-boost interval matters: a randomized phase 1 study to identify the minimum interval necessary to observe the H5 DNA influenza vaccine priming effect. J Infect Dis. 2013 Aug 1;208(3):418-22. doi: 10.1093/infdis/jit180. Epub 2013 Apr 30.
PMID: 23633407DERIVEDKhurana S, Wu J, Dimitrova M, King LR, Manischewitz J, Graham BS, Ledgerwood JE, Golding H. DNA priming prior to inactivated influenza A(H5N1) vaccination expands the antibody epitope repertoire and increases affinity maturation in a boost-interval-dependent manner in adults. J Infect Dis. 2013 Aug 1;208(3):413-7. doi: 10.1093/infdis/jit178. Epub 2013 Apr 30.
PMID: 23633404DERIVEDLedgerwood 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: 21975270DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
Study Record Dates
First Submitted
March 12, 2010
First Posted
March 15, 2010
Study Start
February 25, 2010
Primary Completion
December 12, 2011
Study Completion
December 12, 2011
Last Updated
July 2, 2017
Record last verified: 2011-12-12