Seasonal Influenza DNA Vaccine Prime With Trivalent Inactivated Vaccine (TIV) Boost Compared to TIV Alone

NCT01498718 | Completed Phase 1 DMC

• 1 other identifier: VRC 701
• Study Type: interventional
• Target: 131
• Locations: 1 country
• Sites: 4

Brief Summary

This is a Phase 1b, randomized study in healthy younger (18-50 years) and older (51-70 years) adults to evaluate the safety, tolerability, and immunogenicity of a prime-boost vaccination regimen with an investigational plasmid DNA vaccine directed towards the 2011/12 influenza vaccine strains as a prime followed 36 weeks later by the 2012/13 influenza trivalent inactivated vaccine (TIV) as the booster injection, as compared to placebo prime followed by the 2012/13 seasonal TIV. The hypothesis is that the DNA vaccine will be safe for human administration and that the DNA vaccine prime-TIV boost schedule will elicit a better immune response than the seasonal TIV alone.

Conditions

Influenza

Keywords

Influenza A (H1N1); Influenza A (H3N2); Influenza B; Trivalent Inactivated Vaccine (TIV); Healthy Adults

Outcome Measures

Primary Outcomes (7)

• Frequency of subjects per Group of serious adverse events (SAEs)

  Serious adverse events included any untoward medical occurrence that resulted in death; was life threatening; was a persistent/significant disability/incapacity; required non-elective in-patient hospitalization or prolongation thereof; resulted in a congenital anomaly/birth defect; may have jeopardized the subject or required intervention to prevent one of these outcomes. Association to vaccination was determined by a study clinician licensed to make medical diagnoses.

  Day 0 (after injection) to Week 60 (Visit 07)

• Frequency of Subjects per Group of Solicited Local Reactions After First Study Injection

  Frequency and severity of solicited injection site reactions following first study injection (vaccine group compared to placebo group).

  Within 7 days after first vaccination

• Frequency of Subjects per Group Reporting Solicited Local Reactions After TIV injection

  Frequency and severity of solicited injection site reactions following the TIV booster injection by Group.

  Within 7 days after TIV injection

• Frequency of Subjects per Group Reporting Solicited Systemic Reactions After First Study Injection

  Frequency and severity of solicited systemic reactions following first study injection (vaccine group compared to placebo group).

  Within 7 days after first study injection

• Frequency of Subjects per Group Reporting Solicited Systemic Reactions After TIV injection

  Frequency and severity of solicited systemic reactions following TIV injection.

  Within 7 days after TIV injection

• Frequency by group of all unsolicited adverse events (AEs) after first study injection.

  Frequency of adverse events (AEs) during 28 days after first study injection (vaccine as compared to placebo groups).

  Through Day 28 after first injection

• Frequency by group of all unsolicited adverse events (AEs) after TIV vaccination.

  Frequency of unsolicited adverse events (AEs) during 28 days after TIV vaccination by group.

  Through Day 28 after second vaccincation

Secondary Outcomes (2)

• Proportion of subjects per group with an Hemagglutination Inhibition (HAI) titer ≥ 1:40 or four-fold greater than baseline (Day 0) compared to those who received the seasonal influenza TIV alone.

  Week 40 (4 weeks after TIV)

• Proportion of subjects by group with a four-fold or greater rise from baseline (Day 0) and Week 40 in specific H1, H3 and B neutralizing antibodies

  Week 40 (4 weeks after TIV)

Study Arms (4)

Group 1A (18-50 yrs): DNA vaccine + TIV

EXPERIMENTAL

HA DNA Vaccine (VRC-FLUDNA061-00-VP) at Day 0 and licensed TIV at Week 36

Biological: DNA vaccine; Biological: TIV

Group 2A (51-70 yrs): DNA vaccine + TIV

EXPERIMENTAL

HA DNA Vaccine (VRC-FLUDNA061-00-VP) at Day 0 and licensed TIV at Week 36

Biological: DNA vaccine; Biological: TIV

Group 1B (18-50 yrs): TIV only

PLACEBO COMPARATOR

Phosphate buffered saline (PBS) on Day 0 + TIV at Week 36

Biological: TIV

Group 2B (51-70 yrs): TIV only

PLACEBO COMPARATOR

Phosphate buffered saline (PBS) on Day 0 + TIV at Week 36

Biological: TIV

Interventions

DNA vaccine BIOLOGICAL

VRC-FLUDNA061-00-VP is composed of 3 closed-circular DNA plasmids that encode for the hemagglutinin (HA) from the following 3 strains: A/California/04/2009 (H1N1); A/Perth/16/2009 (H3N2), and B/Brisbane/60/2008. DNA vaccine vials will be supplied at 4 mg/mL and each dose will be 1 mL.

Also known as: VRC-FLUDNA061-00-VP, HA DNA Vaccine, Seasonal influenza trivalent DNA vaccine

Group 1A (18-50 yrs): DNA vaccine + TIV; Group 2A (51-70 yrs): DNA vaccine + TIV

TIV BIOLOGICAL

2012/13 Seasonal Influenza Trivalent Inactivated Vaccine (TIV)

Also known as: Trivalent Inactivated Vaccine

Group 1A (18-50 yrs): DNA vaccine + TIV; Group 1B (18-50 yrs): TIV only; Group 2A (51-70 yrs): DNA vaccine + TIV; Group 2B (51-70 yrs): TIV only

Eligibility Criteria

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

You may qualify if:

• to 70 yrs
• Available for clinical follow-up through Study Week 60
• Able and willing to complete the informed consent process
• Willing to donate blood for sample storage to be used for future research
• Physical exam and lab results without clinically significant findings and a Body Mass Index (BMI) \<40 within the 70 days prior to enrollment
• Has received the 2011/2012 licensed influenza vaccine 8 or more weeks prior to enrollment and agrees to receive the 2012/2013 TIV as part of study participation
• Laboratory Criteria within 70 days prior to enrollment:
• Hemoglobin within institutional normal limits
• White blood cells either within institutional normal range or site physician approves 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 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 12 weeks after the first study vaccination

You may not qualify if:

• Women Specific:
• Breast-feeding or planning to become pregnant during the 12 weeks after enrollment 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
• 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 prophylaxis or therapy
• 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, acquired angioedema, 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

Sponsors & Collaborators

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

Study Sites (4)

Hope Clinic of the Emory Vaccine Center

Decatur, Georgia, 30030, United States

Location

St. Louis University - Doisy Research Center

St Louis, Missouri, 63104, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Related Publications (4)

• 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

• Wei CJ, Boyington JC, McTamney PM, Kong WP, Pearce MB, Xu L, Andersen H, Rao S, Tumpey TM, Yang ZY, Nabel GJ. Induction of broadly neutralizing H1N1 influenza antibodies by vaccination. Science. 2010 Aug 27;329(5995):1060-4. doi: 10.1126/science.1192517. Epub 2010 Jul 15.

  PMID: 20647428 BACKGROUND

• Ledgerwood JE, Bellamy AR, Belshe R, Bernstein DI, Edupuganti S, Patel SM, Renehan P, Zajdowicz T, Schwartz R, Koup R, Bailer RT, Yamshchikov GV, Enama ME, Sarwar U, Larkin B, Graham BS; VRC 701 study team. DNA priming for seasonal influenza vaccine: a phase 1b double-blind randomized clinical trial. PLoS One. 2015 May 7;10(5):e0125914. doi: 10.1371/journal.pone.0125914. eCollection 2015.

  PMID: 25950433 DERIVED

MeSH Terms

Conditions

Influenza, Human; Orthomyxoviridae Infections

Interventions

Vaccines, DNA

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Nucleic Acid-Based Vaccines; Vaccines, Synthetic; Recombinant Proteins; Proteins; Amino Acids, Peptides, and Proteins; Vaccines; Biological Products; Complex Mixtures; Antigens; Biological Factors

Study Officials

• Julie Ledgerwood, D.O.

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

  STUDY CHAIR

• Barney S Graham, M.D., Ph.D.

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

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 21, 2011
• First Posted: December 23, 2011
• Study Start: December 1, 2011
• Primary Completion: April 1, 2013
• Study Completion: April 1, 2013
• Last Updated: March 24, 2016

Record last verified: 2016-03

Locations

US (4)