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

NCT01676402 | Completed Phase 1

• 1 other identifier: VRC 703
• Study Type: interventional
• Target: 316
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Influenza

Keywords

Influenza A (H1); Influenza A (H3); Influenza B; DNA Vaccine; Trivalent Inactivated Vaccine (TIV); Healthy Adults; Intradermal (ID)

Outcome Measures

Primary Outcomes (11)

• 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.

  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.

  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.

  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.

  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.

  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.

  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

  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.

  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.

  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.

  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.

  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

  3 weeks after each study injection

• Geometric Mean HAI Titer for each of the 2012/13 and 2013/14 influenza vaccine strains

  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

  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

  3 weeks after each study injection

Study Arms (6)

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

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

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

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

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

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

Biological: Seasonal Influenza DNA vaccine; Biological: TIV

Interventions

Seasonal Influenza DNA vaccine BIOLOGICAL

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.

Also known as: VRC-FLUDNA063-00-VP, HA DNA Vaccine, Seasonal influenza trivalent DNA vaccine

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

TIV BIOLOGICAL

2012/13, 2013/14 Seasonal Influenza Trivalent Inactivated Vaccine (TIV)

Also known as: 2012/13 Seasonal Influenza TIV (Fluzone), 2013/14 Seasonal Influenza TIV (Fluzone)

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

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

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 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
• 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

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• The Emmes Company, LLC: collaborator

Study Sites (4)

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

University of Iowa Hospitals & Clinics

Iowa City, Iowa, 52242, United States

Location

Saint Louis University - Doisy Research Center

St Louis, Missouri, 63104, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

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: 21975270 BACKGROUND

• 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.

  PMID: 19779298 BACKGROUND

• 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.

  PMID: 31532789 RESULT

MeSH Terms

Conditions

Influenza, Human

Interventions

Influenza Vaccines

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Study Officials

• Barney S Graham, M.D., Ph.D.

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

  STUDY DIRECTOR

• Julie Ledgerwood, DO

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

  STUDY CHAIR

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: August 13, 2012
• First Posted: August 30, 2012
• Study Start: August 1, 2012
• Primary Completion: April 1, 2014
• Study Completion: April 1, 2014
• Last Updated: August 25, 2022

Record last verified: 2022-08

Locations

US (4)