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

This study has been completed.
Sponsor:
Collaborator:
The EMMES Corporation
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT01498718
First received: December 21, 2011
Last updated: July 15, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention Phase
Influenza
Biological: DNA vaccine
Biological: TIV
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Double-Blind, Randomized Phase 1b Study of 2011/12 Influenza Investigational DNA Vaccine, VRC-FLUDNA061-00-VP, Followed by 2012/13 Trivalent Inactivated Vaccine (TIV) Compared to 2012/13 TIV Alone in Healthy Adults

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Frequency of subjects per Group of serious adverse events (SAEs) [ Time Frame: Day 0 (after injection) to Week 60 (Visit 07) ] [ Designated as safety issue: Yes ]
    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.

  • Frequency of Subjects per Group of Solicited Local Reactions After First Study Injection [ Time Frame: Within 7 days after first vaccination ] [ Designated as safety issue: Yes ]
    Frequency and severity of solicited injection site reactions following first study injection (vaccine group compared to placebo group).

  • Frequency of Subjects per Group Reporting Solicited Local Reactions After TIV injection [ Time Frame: Within 7 days after TIV injection ] [ Designated as safety issue: Yes ]
    Frequency and severity of solicited injection site reactions following the TIV booster injection by Group.

  • Frequency of Subjects per Group Reporting Solicited Systemic Reactions After First Study Injection [ Time Frame: Within 7 days after first study injection ] [ Designated as safety issue: Yes ]
    Frequency and severity of solicited systemic reactions following first study injection (vaccine group compared to placebo group).

  • Frequency of Subjects per Group Reporting Solicited Systemic Reactions After TIV injection [ Time Frame: Within 7 days after TIV injection ] [ Designated as safety issue: Yes ]
    Frequency and severity of solicited systemic reactions following TIV injection.

  • Frequency by group of all unsolicited adverse events (AEs) after first study injection. [ Time Frame: Through Day 28 after first injection ] [ Designated as safety issue: Yes ]
    Frequency of adverse events (AEs) during 28 days after first study injection (vaccine as compared to placebo groups).

  • Frequency by group of all unsolicited adverse events (AEs) after TIV vaccination. [ Time Frame: Through Day 28 after second vaccincation ] [ Designated as safety issue: Yes ]
    Frequency of unsolicited adverse events (AEs) during 28 days after TIV vaccination by group.


Secondary Outcome Measures:
  • 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. [ Time Frame: Week 40 (4 weeks after TIV) ] [ Designated as safety issue: No ]
    Blood is collected from all subjects at baseline and at 4 weeks after TIV (Week 40) for testing in an HAI assay for each of the 3 strains of influenza in the vaccine. A positive response is 1:40 or greater (or a 4-fold increase over baseline if positive at baseline). Groups are compared for statistically significant differences.

  • 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 [ Time Frame: Week 40 (4 weeks after TIV) ] [ Designated as safety issue: No ]
    Blood is collected from all subjects at baseline (Day 0) and at Week 40 (4 weeks after TIV) for testing in a neutralizing antibody assay for strain-specific H1, H3 and B antigens. A positive response is a four-fold rise or greater from baseline.


Enrollment: 131
Study Start Date: December 2011
Study Completion Date: April 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1A (18-50 yrs): DNA vaccine + TIV
HA DNA Vaccine (VRC-FLUDNA061-00-VP) at Day 0 and licensed TIV at Week 36
Biological: DNA vaccine
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.
Other Names:
  • VRC-FLUDNA061-00-VP
  • HA DNA Vaccine
  • Seasonal influenza trivalent DNA vaccine
Biological: TIV
2012/13 Seasonal Influenza Trivalent Inactivated Vaccine (TIV)
Other Name: Trivalent Inactivated Vaccine
Experimental: Group 2A (51-70 yrs): DNA vaccine + TIV
HA DNA Vaccine (VRC-FLUDNA061-00-VP) at Day 0 and licensed TIV at Week 36
Biological: DNA vaccine
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.
Other Names:
  • VRC-FLUDNA061-00-VP
  • HA DNA Vaccine
  • Seasonal influenza trivalent DNA vaccine
Biological: TIV
2012/13 Seasonal Influenza Trivalent Inactivated Vaccine (TIV)
Other Name: Trivalent Inactivated Vaccine
Placebo Comparator: Group 1B (18-50 yrs): TIV only
Phosphate buffered saline (PBS) on Day 0 + TIV at Week 36
Biological: TIV
2012/13 Seasonal Influenza Trivalent Inactivated Vaccine (TIV)
Other Name: Trivalent Inactivated Vaccine
Placebo Comparator: Group 2B (51-70 yrs): TIV only
Phosphate buffered saline (PBS) on Day 0 + TIV at Week 36
Biological: TIV
2012/13 Seasonal Influenza Trivalent Inactivated Vaccine (TIV)
Other Name: Trivalent Inactivated Vaccine

Detailed Description:

Vaccines are an effective way of preventing influenza infection and transmission in humans. Although licensed influenza vaccines are available, ways to improve influenza vaccines continue to be studied. Annually, the World Health Organization (WHO) and the U.S FDA make recommendations on the composition of the seasonal influenza vaccine, with recommendations for the Northern Hemisphere (NH) and for the Southern Hemisphere (SH) considered at different times based on epidemiology data. The annually licensed influenza vaccines consist of 3 components: an Influenza A (H1N1) strain, an Influenza A (H3N2) strain, and an influenza B strain. The current U.S. FDA-licensed influenza vaccines depend upon labor-intensive methods that limit manufacturing capacity and which do not induce broad immune responses to various strains of influenza. The vaccine composition requires frequent adjustment for emerging influenza strains.

The need for influenza vaccines that are more immunogenic and able to induce a more universal immune response against a broad spectrum of influenza strains is well recognized. Earlier laboratory and clinical studies together suggest that an investigational DNA vaccine encoding for the influenza hemagglutinin protein(HA DNA vaccine) administered as a prime, followed by a boost with a traditional inactivated influenza vaccine, may induce a stronger immune response against various influenza strains and with improved durability. The interval of time between the prime vaccination and the boost vaccination is important for the strength of the immune response.

This clinical trial will evaluate the safety, tolerability and immune responses to the investigational HA DNA vaccine prime-TIV boost schedule compared to a placebo prime-TIV boost schedule when the time between the prime and boost is 36 weeks.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 18 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

Exclusion Criteria:

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
  • 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 intramuscular (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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01498718

Locations
United States, Georgia
Hope Clinic of the Emory Vaccine Center
Decatur, Georgia, United States, 30030
United States, Missouri
St. Louis University - Doisy Research Center
St. Louis, Missouri, United States, 63104
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
United States, Texas
Baylor College of Medicine
Houston, Texas, United States, 77030
Sponsors and Collaborators
The EMMES Corporation
Investigators
Study Chair: Julie Ledgerwood, D.O. Deputy Chief, Clinical Trials Core Vaccine Research Center, NIAID, NIH
Study Director: Barney S Graham, M.D., Ph.D. Chief, Clinical Trials Core Vaccine Research Center, NIAID, NIH
  More Information

Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT01498718     History of Changes
Other Study ID Numbers: VRC 701, VRC 701
Study First Received: December 21, 2011
Last Updated: July 15, 2013
Health Authority: United States: Federal Government
United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Influenza A (H1N1)
Influenza A (H3N2)
Influenza B
Trivalent Inactivated Vaccine (TIV)
Healthy Adults

Additional relevant MeSH terms:
Influenza, Human
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on October 01, 2014