InfluenzaPhase 1NCT01676402

Seasonal Influenza HA DNA With Trivalent Inactivated Vaccine (TIV) Administered ID or IM in Healthy Adults 18-70 Years

A Phase 1 study testing Seasonal Influenza DNA vaccine and TIV in people with Influenza, run by National Institute of Allergy and Infectious Diseases (NIAID) at 4 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 70 yearsHealthy volunteers can take part
Conditions the study is for: Influenza
What is being tested?: Seasonal Influenza DNA vaccine and TIV
Type of treatment: Vaccines
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 316 participants
Where: 4 sitesUnited States
Study dates: Aug 2012to Apr 2014
Phase: Phase 1
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 70 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

A subject must meet all of the following criteria:
Healthy adults, 18 to 70 years old; volunteers who will be older than 64 during the 2013/2014 influenza season will not be enrolled after 11/16/2012.
Available for clinical follow-up
Able and willing to complete the informed consent process
Willing to donate blood for sample storage to be used for future research
Physical examination and laboratory results without clinically significant findings and a Body Mass Index (BMI) ≤40 within the 70 days prior to enrollment

Show all 16Show fewer

Has not yet received the current year (2012/13) influenza vaccine prior to enrollment and agrees to receive seasonal influenza vaccines during study participation only from the study site
Laboratory Criteria within 70 days prior to enrollment:
Hemoglobin within institutional normal limits
White blood cells either within institutional normal range or accompanied by site physician approval as consistent with healthy adult status
Platelets = 125,000 - 500,000/mm3
Alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN)
Serum creatinine ≤ 1 x ULN based on site institutional normal range
Criteria applicable to women of childbearing potential:
Negative human chorionic gonadotropin (β-HCG) pregnancy test (urine or serum) on day of enrollment
Agree to use an effective means of birth control from 21 days prior to enrollment through 3 weeks after the second study vaccination

Who cannot join

A subject will be excluded if one or more of the following conditions apply:
Women Specific:
Breast-feeding or planning to become pregnant while participating in the study
Subject has received any of the following substances:
More than 10 days of systemic immunosuppressive medications or cytotoxic medications within the 12 weeks prior to enrollment or any within the 14 days prior to enrollment
Blood products within 16 weeks prior to enrollment

Show all 26Show fewer

Immunoglobulin within 8 weeks prior to enrollment
Investigational research agents within 28 days (4 weeks) prior to enrollment or planning to receive investigational products while on the study.
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
Current anti-tuberculosis (TB) prophylaxis or therapy
Subject has a history of any of the following clinically significant conditions:
Contraindication to receiving an FDA-approved seasonal influenza vaccination
Serious reactions to vaccines that preclude receipt of study vaccinations, as determined by the site investigator
Hereditary angioedema (HAE), acquired angioedema (AAE), or idiopathic forms of angioedema
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
Diabetes mellitus type I
Thyroid disease that is not well-controlled
Generalized idiopathic urticaria within the 1 year prior to enrollment
Hypertension that is not well controlled
Bleeding disorder diagnosed by a doctor (e.g. factor deficiency, coagulopathy, or platelet disorder requiring special precautions), or significant bruising or bleeding difficulties with IM injections or blood draws, or use of blood thinners such as Coumadin or Plavix®
Malignancy that is active or treated malignancy for which there is not reasonable assurance of sustained cure or malignancy that is likely to recur during the period of the study
Seizure disorder other than: 1) febrile seizures, 2) seizures secondary to alcohol withdrawal more than 3 years ago, or 3) seizures for which no treatment has been required within the 3 years prior to enrollment
Asplenia, functional asplenia or any condition resulting in the absence or removal of the spleen
Guillain-Barré Syndrome
Psychiatric condition that precludes compliance with the protocol; past or present psychoses; disorder requiring lithium; or within 5 years prior to enrollment, a history of suicide plan or attempt
Any medical, psychiatric, or other condition that, in the judgment of the investigator, is a contraindication to protocol participation or impairs ability to give informed consent

Trial locations and contacts

4 sites in 1 country.

United States4 sites

Baylor College of Medicine
Houston, Texas, 77030
University of Iowa Hospitals & Clinics
Iowa City, Iowa, 52242
Saint Louis University - Doisy Research Center
St Louis, Missouri, 63104
Stanford University School of Medicine
Stanford, California, 94305

Other trials in United States

About this study

Official title: Open-Label, Randomized Phase 1b Study of the Safety & Immunogenicity of Investigational Seasonal Influenza DNA Vaccine Followed by TIV Administered Intradermally (ID) or Intramuscularly (IM) in Healthy Adults 18-70 Years

This is a Phase Ib study in healthy adults (18-70 years) to evaluate the safety, tolerability, and immunogenicity of same season and sequential season vaccination schedules consisting of the 2012/2013 seasonal influenza DNA vaccine (HA DNA) and licensed trivalent influenza vaccine (TIV) administered intradermally (ID) or intramuscularly (IM). The hypothesis is that evaluation of these investigational schedules will inform development of novel influenza vaccine strategies that may offer improved and cross-protective immunity against antigenically diverse influenza strains.

Read the 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 propose to use DNA vaccine antigen delivery to induce immune responses against native hemagglutinin (HA) structures prior to boosting with licensed TIV ID or with TIV IM.

The study will allow evaluation of the safety and immunogenicity of same season and sequential season vaccination schedules. The same season regimens (2012/13 prime and boost with a 14 week interval) consist of HA DNA prime with TIV ID boost -- or -- HA DNA prime with TIV IM boost. The active comparator for these schedules are TIV ID or TIV IM alone because a single dose of TIV is the standard for adult influenza vaccination within a single season. The sequential season regimens (2012/13 prime and 2013/14 boost) consist of concurrent administration (in different arms) of HA DNA and TIV ID prime with TIV ID boost -- or -- HA DNA and TIV IM prime with TIV IM boost. The active comparator for these regimens will be TIV ID followed by TIV ID boost -- or -- TIV IM followed by TIV IM boost, administered sequential seasons consistent with as typical pattern of use for these licensed vaccines. Evaluation of the investigational schedules and active comparator schedules will inform development of novel influenza vaccine strategies that may offer improved and cross-protective immunity against diverse influenza strains.

Conditions: Influenza
Being tested: Seasonal Influenza DNA vaccine, TIV
Keywords: Influenza A (H1), Influenza A (H3), Influenza B, DNA Vaccine, Trivalent Inactivated Vaccine (TIV), Healthy Adults, Intradermal (ID)
Medical subject headings: Influenza, Human

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Seasonal Influenza DNA vaccineBiological
Also called VRC-FLUDNA063-00-VP, HA DNA Vaccine, Seasonal influenza trivalent 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 4 mg dosage is administered as a 1 mL volume.
TIVBiological
Also called 2012/13 Seasonal Influenza TIV (Fluzone), 2013/14 Seasonal Influenza TIV (Fluzone)
2012/13, 2013/14 Seasonal Influenza Trivalent Inactivated Vaccine (TIV)

Study groups in NCT01676402
Study group	Role	What they receive
Group 1: HA DNA + TIV ID	Experimental	2012/13 seasonal influenza DNA Vaccine (VRC-FLUDNA063-00-VP) at Day 0 and licensed 2012/13 TIV ID at Week 14±2 wks Receives: Biological: Seasonal Influenza DNA vaccine; Biological: TIV
Group 2: HA DNA + TIV IM	Experimental	2012/13 seasonal influenza DNA Vaccine (VRC-FLUDNA063-00-VP) at Day 0 and licensed 2012/13 TIV IM at Week 14±2 wks Receives: Biological: Seasonal Influenza DNA vaccine; Biological: TIV
Group 3: TIV ID + TIV ID	Experimental	licensed 2012/13 TIV ID at Day 0 and licensed 2013/14 TIV ID at Week 44±2 weeks Receives: Biological: TIV
Group 4: TIV IM + TIV IM	Experimental	2012/13 licensed TIV IM at Day 0 and licensed 2013/14 TIV IM at Week 44±2 weeks Receives: Biological: TIV
Group 5: (HA DNA and TIV ID) + TIV ID	Experimental	2012/13 seasonal influenza DNA Vaccine (VRC-FLUDNA063-00-VP) and licensed 2012/13 TIV ID at Day 0 followed by licensed 2013/14 TIV ID at Week 44±2 weeks Receives: Biological: Seasonal Influenza DNA vaccine; Biological: TIV
Group 6: (HA DNA and TIV IM) + TIV IM	Experimental	2012/13 seasonal influenza DNA Vaccine (VRC-FLUDNA063-00-VP) and licensed 2012/13 TIV IM at Day 0 followed by licensed 2013/14 TIV IM at Week 44±2 weeks Receives: Biological: Seasonal Influenza DNA vaccine; Biological: TIV

What is being measured

The primary outcome is the main question the study is designed to answer.

Incidence of solicited adverse events after the first injection
Incidence is reported for solicited events for 7 days after the first injection. For all Groups the collection period for solicited adverse events following the first injection Day 0 to Day 7.
Measured: Day 0 to Day 7
Incidence of solicited adverse events after the second injection
Incidence is reported for solicited events for 7 days after the second injection. The period of solicitation is defined by the actual day of second injection.
Measured: Day of injection to 7 days after second injection
Incidence of unsolicited adverse events of any severity 28 days after the first injection
Incidence is reported for unsolicited events for 28 days after the first injection. For all Groups the reporting period for unsolicited adverse events following the first injection Day 0 to Day 28.
Measured: Day 0 to Day 28
Incidence of unsolicited adverse events of any severity for 28 days after the second injection
The 28 day period following second injection is defined by the actual day of second injection.
Measured: Day of injection to 28 days after injection
Incidence of serious adverse events or new chronic medical conditions through 24 weeks after the 2nd injection
The day of second injection varies by group; the duration of time from Day 0 through 24 weeks after second injection is defined by the actual day of second injection.
Measured: Day 0 to 24 weeks after second injection
Number of subjects with influenza or influenza-like illnesses (ILI)
The day of second injection varies by group; the duration of time from Day 0 through 24 weeks after second injection is defined by the actual day of second injection.
Measured: Day 0 to 24 weeks after second injection
Mean change from baseline in safety laboratory measures
At Day 21 (window Day 21-28) blood will be drawn to measure hemoglobin, hematocrit, red blood cells (RBC), white blood cells (WBC), mean corpuscular volume (MCV), platelets
Measured: Day 21
Proportion of subjects with seroconversion for each of the 2012/13 influenza vaccine strains (Group 1 and Group 2)
Seroconversion is defined a pre-vaccination strain-specific HAI titer <1:10 and a post-vaccination hemagglutination inhibition (HAI) titer ≥1:40 or a pre-vaccination.
Blood is collected at baseline (Day 0) and at 3 weeks following completion of the 2012/2013 vaccination regimen (3 weeks after 2012/13 TIV ID or TIV IM boost for Group 1 and Group 2, Day 119) for testing in an HAI assay for each of the influenza strains influenza in the 2012/2013 influenza vaccines.
Measured: Day 119
Proportion of subjects with seroconversion for each of the 2012/13 influenza vaccine strains (Group 3 and Group 4)
Blood is collected at baseline (Day 0) and at 3 weeks following completion of the 2012/2013 prime injection (3 weeks after 2012/13 TIV ID or TIV IM prime Group 3 and Group 4, Day 21) for testing in an HAI assay for each of the influenza strains influenza in the 2012/2013 influenza vaccines.
Measured: Day 21
Geometric Mean HAI Titer for each of the 2012/13 influenza vaccine strains (Group 1 and Group 2)
Blood is collected 3 weeks following completion of the 2012/2013 vaccination regimen 3 weeks after 2012/13 TIV ID or TIV IM boost for (Group 1 and Group 2, Day 119) for testing in an HAI assay for each of the influenza strains influenza in the 2012/2013 influenza vaccines.
Measured: Day 119
Geometric Mean HAI titer for each of the 2012/13 influenza vaccine strains (Group 3 and Group 4)
Blood is collected 3 weeks following completion of the 2012/2013 prime injection (3 weeks after 2012/13 TIV ID or TIV IM prime Group 3 and Group 4, Day 21) for testing in an HAI assay for each of the influenza strains influenza in the 2012/2013 influenza vaccines.
Measured: 3 weeks after completion of the HA DNA prime, Day 21

Secondary outcomes (4)

Seroconversion for each of the 2012/13 and 2013/14 influenza vaccine strains
For all study groups, blood is collected from all subjects at baseline and at 3 weeks following each study injection for testing in an HAI assay for each of the influenza strains influenza in the 2012/2013 and 2013/2014 influenza vaccines. Seroconversion is defined a pre-vaccination strain-specific HAI titer <1:10 and a post-vaccination HAI titer ≥1:40 or a pre-vaccination.
Measured: 3 weeks after each study injection
Geometric Mean HAI Titer for each of the 2012/13 and 2013/14 influenza vaccine strains
For all study groups, blood is collected from all subjects at baseline and at 3 weeks following each study injection for testing in an HAI assay for each of the influenza strains influenza in the 2012/2013 and 2013/2014 influenza vaccines.
Measured: 3 weeks after each study injection
Proportion of subjects with four-fold rise from baseline for each of the 2012/13 and 2013/14 influenza vaccine strain-specific H1, H3, and B neutralizing antibodies
For all study groups, blood is collected from all subjects at baseline and at 3 weeks following each study injection for testing 2012/2013 and 2013/2014 influenza vaccine strain-specific H1, H3, and B neutralizing antibodies.
Measured: 3 weeks after each study injection
Geometric Mean neutralization titer of 2012/13 and 2013/14 influenza vaccine strain-specific H1, H3, and B neutralizing antibodies
For all study groups, blood is collected from all subjects at baseline and at 3 weeks following each study injection for testing 2012/2013 and 2013/2014 influenza vaccine strain-specific H1, H3, and B neutralizing antibodies.
Measured: 3 weeks after each study injection

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Aug 2012Apr 2014

First posted30 Aug 2012 (estimated)
Study startAug 2012
Primary completionApr 2014
Study completionApr 2014

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (3)Papers the sponsor has linked to this study.
Other trials for InfluenzaStudies of the same condition, open and under way.
More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 316 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01676402
Sponsor's protocol ID: VRC 703
Other IDs: VRC 703
Status last verified: Aug 2022
First submitted: 13 Aug 2012
Last updated: 25 Aug 2022
Results posted: No
Data monitoring committee: No

Publications

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.
PubMed 21975270
Ledgerwood 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.
PubMed 19779298
Carter C, Houser KV, Yamshchikov GV, Bellamy AR, May J, Enama ME, Sarwar U, Larkin B, Bailer RT, Koup R, Chen GL, Patel SM, Winokur P, Belshe R, Dekker CL, Graham BS, Ledgerwood JE; VRC 703 study team. Safety and immunogenicity of investigational seasonal influenza hemagglutinin DNA vaccine followed by trivalent inactivated vaccine administered intradermally or intramuscularly in healthy adults: An open-label randomized phase 1 clinical trial. PLoS One. 2019 Sep 18;14(9):e0222178. doi: 10.1371/journal.pone.0222178. eCollection 2019.
PubMed 31532789

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 25 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Open-Label, Randomized Phase 1b Study of the Safety & Immunogenicity of Investigational Seasonal Influenza DNA Vaccine Followed by TIV Administered Intradermally (ID) or Intramuscularly (IM) in Healthy Adults 18-70 Years
ClinicalTrials.gov ID: NCT01676402
Acronym / sponsor ID: VRC 703
Conditions: Influenza
Keywords: Influenza A (H1), Influenza A (H3), Influenza B, DNA Vaccine, Trivalent Inactivated Vaccine (TIV), Healthy Adults, Intradermal (ID)
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 316 participants (actual)
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
Collaborators: The Emmes Company, LLC
Study start: Aug 2012
Primary completion: Apr 2014 (actual)
Study completion: Apr 2014 (actual)
First posted: 30 Aug 2012 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

In this protocol we propose to use DNA vaccine antigen delivery to induce immune responses against native hemagglutinin (HA) structures prior to boosting with licensed TIV ID or with TIV IM.

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 6

Arm	Type	Receives
Group 1: HA DNA + TIV ID	Experimental	Biological: Seasonal Influenza DNA vaccine, Biological: TIV2012/13 seasonal influenza DNA Vaccine (VRC-FLUDNA063-00-VP) at Day 0 and licensed 2012/13 TIV ID at Week 14±2 wks
Group 2: HA DNA + TIV IM	Experimental	Biological: Seasonal Influenza DNA vaccine, Biological: TIV2012/13 seasonal influenza DNA Vaccine (VRC-FLUDNA063-00-VP) at Day 0 and licensed 2012/13 TIV IM at Week 14±2 wks
Group 3: TIV ID + TIV ID	Experimental	Biological: TIVlicensed 2012/13 TIV ID at Day 0 and licensed 2013/14 TIV ID at Week 44±2 weeks
Group 4: TIV IM + TIV IM	Experimental	Biological: TIV2012/13 licensed TIV IM at Day 0 and licensed 2013/14 TIV IM at Week 44±2 weeks
Group 5: (HA DNA and TIV ID) + TIV ID	Experimental	Biological: Seasonal Influenza DNA vaccine, Biological: TIV2012/13 seasonal influenza DNA Vaccine (VRC-FLUDNA063-00-VP) and licensed 2012/13 TIV ID at Day 0 followed by licensed 2013/14 TIV ID at Week 44±2 weeks
Group 6: (HA DNA and TIV IM) + TIV IM	Experimental	Biological: Seasonal Influenza DNA vaccine, Biological: TIV2012/13 seasonal influenza DNA Vaccine (VRC-FLUDNA063-00-VP) and licensed 2012/13 TIV IM at Day 0 followed by licensed 2013/14 TIV IM at Week 44±2 weeks

Who may qualify

Ages: 18 to 70 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (16 listed)

Healthy adults, 18 to 70 years old; volunteers who will be older than 64 during the 2013/2014 influenza season will not be enrolled after 11/16/2012.
Available for clinical follow-up
Able and willing to complete the informed consent process
Willing to donate blood for sample storage to be used for future research
Physical examination and laboratory results without clinically significant findings and a Body Mass Index (BMI) ≤40 within the 70 days prior to enrollment

Key exclusion criteria (26 listed)

Breast-feeding or planning to become pregnant while participating in the study
More than 10 days of systemic immunosuppressive medications or cytotoxic medications within the 12 weeks prior to enrollment or any within the 14 days prior to enrollment
Blood products within 16 weeks prior to enrollment
Immunoglobulin within 8 weeks prior to enrollment
Investigational research agents within 28 days (4 weeks) prior to enrollment or planning to receive investigational products while on the study.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Seasonal Influenza DNA vaccineAlso: VRC-FLUDNA063-00-VP, HA DNA Vaccine, Seasonal influenza trivalent DNA vaccineVRC-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 4 mg dosage is administered as a 1 mL volume.	Biological	Group 1: HA DNA + TIV ID, Group 2: HA DNA + TIV IM, Group 5: (HA DNA and TIV ID) + TIV ID, Group 6: (HA DNA and TIV IM) + TIV IM
TIVAlso: 2012/13 Seasonal Influenza TIV (Fluzone), 2013/14 Seasonal Influenza TIV (Fluzone)2012/13, 2013/14 Seasonal Influenza Trivalent Inactivated Vaccine (TIV)	Biological	Group 1: HA DNA + TIV ID, Group 2: HA DNA + TIV IM, Group 3: TIV ID + TIV ID, Group 4: TIV IM + TIV IM, Group 5: (HA DNA and TIV ID) + TIV ID, Group 6: (HA DNA and TIV IM) + TIV IM

Primary outcome

Incidence of solicited adverse events after the first injection
Time frame: Day 0 to Day 7
Incidence is reported for solicited events for 7 days after the first injection. For all Groups the collection period for solicited adverse events following the first injection Day 0 to Day 7.
Incidence of solicited adverse events after the second injection
Time frame: Day of injection to 7 days after second injection
Incidence is reported for solicited events for 7 days after the second injection. The period of solicitation is defined by the actual day of second injection.
Incidence of unsolicited adverse events of any severity 28 days after the first injection
Time frame: Day 0 to Day 28
Incidence is reported for unsolicited events for 28 days after the first injection. For all Groups the reporting period for unsolicited adverse events following the first injection Day 0 to Day 28.
Incidence of unsolicited adverse events of any severity for 28 days after the second injection
Time frame: Day of injection to 28 days after injection
The 28 day period following second injection is defined by the actual day of second injection.
Incidence of serious adverse events or new chronic medical conditions through 24 weeks after the 2nd injection
Time frame: Day 0 to 24 weeks after second injection
The day of second injection varies by group; the duration of time from Day 0 through 24 weeks after second injection is defined by the actual day of second injection.
Number of subjects with influenza or influenza-like illnesses (ILI)
Time frame: Day 0 to 24 weeks after second injection
The day of second injection varies by group; the duration of time from Day 0 through 24 weeks after second injection is defined by the actual day of second injection.
Mean change from baseline in safety laboratory measures
Time frame: Day 21
At Day 21 (window Day 21-28) blood will be drawn to measure hemoglobin, hematocrit, red blood cells (RBC), white blood cells (WBC), mean corpuscular volume (MCV), platelets
Proportion of subjects with seroconversion for each of the 2012/13 influenza vaccine strains (Group 1 and Group 2)
Time frame: Day 119
Seroconversion is defined a pre-vaccination strain-specific HAI titer <1:10 and a post-vaccination hemagglutination inhibition (HAI) titer ≥1:40 or a pre-vaccination. Blood is collected at baseline (Day 0) and at 3 weeks following completion of the 2012/2013 vaccination regimen (3 weeks after 2012/13 TIV ID or TIV IM boost for Group 1 and Group 2, Day 119) for testing in an HAI assay for each of the influenza strains influenza in the 2012/2013 influenza vaccines.
Proportion of subjects with seroconversion for each of the 2012/13 influenza vaccine strains (Group 3 and Group 4)
Time frame: Day 21
Blood is collected at baseline (Day 0) and at 3 weeks following completion of the 2012/2013 prime injection (3 weeks after 2012/13 TIV ID or TIV IM prime Group 3 and Group 4, Day 21) for testing in an HAI assay for each of the influenza strains influenza in the 2012/2013 influenza vaccines.
Geometric Mean HAI Titer for each of the 2012/13 influenza vaccine strains (Group 1 and Group 2)
Time frame: Day 119
Blood is collected 3 weeks following completion of the 2012/2013 vaccination regimen 3 weeks after 2012/13 TIV ID or TIV IM boost for (Group 1 and Group 2, Day 119) for testing in an HAI assay for each of the influenza strains influenza in the 2012/2013 influenza vaccines.
Geometric Mean HAI titer for each of the 2012/13 influenza vaccine strains (Group 3 and Group 4)
Time frame: 3 weeks after completion of the HA DNA prime, Day 21
Blood is collected 3 weeks following completion of the 2012/2013 prime injection (3 weeks after 2012/13 TIV ID or TIV IM prime Group 3 and Group 4, Day 21) for testing in an HAI assay for each of the influenza strains influenza in the 2012/2013 influenza vaccines.

4 secondary outcomes

Seroconversion for each of the 2012/13 and 2013/14 influenza vaccine strains
Time frame: 3 weeks after each study injection
Geometric Mean HAI Titer for each of the 2012/13 and 2013/14 influenza vaccine strains
Time frame: 3 weeks after each study injection
Proportion of subjects with four-fold rise from baseline for each of the 2012/13 and 2013/14 influenza vaccine strain-specific H1, H3, and B neutralizing antibodies
Time frame: 3 weeks after each study injection
Geometric Mean neutralization titer of 2012/13 and 2013/14 influenza vaccine strain-specific H1, H3, and B neutralizing antibodies
Time frame: 3 weeks after each study injection

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 25 Aug 2022.
Background: PubMed 21975270Ledgerwood 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.
Background: PubMed 19779298Ledgerwood 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.
Results publication: PubMed 31532789Carter C, Houser KV, Yamshchikov GV, Bellamy AR, May J, Enama ME, Sarwar U, Larkin B, Bailer RT, Koup R, Chen GL, Patel SM, Winokur P, Belshe R, Dekker CL, Graham BS, Ledgerwood JE; VRC 703 study team. Safety and immunogenicity of investigational seasonal influenza hemagglutinin DNA vaccine followed by trivalent inactivated vaccine administered intradermally or intramuscularly in healthy adults: An open-label randomized phase 1 clinical trial. PLoS One. 2019 Sep 18;14(9):e0222178. doi: 10.1371/journal.pone.0222178. eCollection 2019.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Barney S Graham, M.D., Ph.D. study director

Chief, Clinical Trials Core Vaccine Research Center, NIAID, NIH

Julie Ledgerwood, DO study chair

Deputy Chief, Clinical Trials Core Vaccine Research Center, NIAID, NIH

4 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Seasonal Influenza DNA vaccine and TIV in people with Influenza, run by National Institute of Allergy and Infectious Diseases (NIAID) at 4 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of solicited adverse events after the first injection (time frame: Day 0 to Day 7). The study lists 11 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01676402, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Aug 2022.