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

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

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.

Studie Overzicht

Toestand

Voltooid

Conditie

Gedetailleerde beschrijving

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.

Studietype

Ingrijpend

Inschrijving (Werkelijk)

131

Fase

  • Fase 1

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

    • Georgia
      • Decatur, Georgia, Verenigde Staten, 30030
        • Hope Clinic of the Emory Vaccine Center
    • Missouri
      • St. Louis, Missouri, Verenigde Staten, 63104
        • St. Louis University - Doisy Research Center
    • Ohio
      • Cincinnati, Ohio, Verenigde Staten, 45229
        • Cincinnati Children's Hospital Medical Center
    • Texas
      • Houston, Texas, Verenigde Staten, 77030
        • Baylor College of Medicine

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar tot 70 jaar (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Ja

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

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

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Preventie
  • Toewijzing: Gerandomiseerd
  • Interventioneel model: Parallelle opdracht
  • Masker: Verdrievoudigen

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: Group 1A (18-50 yrs): DNA vaccine + TIV
HA DNA Vaccine (VRC-FLUDNA061-00-VP) at Day 0 and licensed TIV at Week 36
2012/13 Seizoensinfluenza trivalent geïnactiveerd vaccin (TIV)
Andere namen:
  • Trivalent Inactivated 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.
Andere namen:
  • HA DNA-vaccin
  • Trivalent DNA-vaccin tegen seizoensgriep
  • VRC-FLUDNA061-00-VP
Experimenteel: Group 2A (51-70 yrs): DNA vaccine + TIV
HA DNA Vaccine (VRC-FLUDNA061-00-VP) at Day 0 and licensed TIV at Week 36
2012/13 Seizoensinfluenza trivalent geïnactiveerd vaccin (TIV)
Andere namen:
  • Trivalent Inactivated 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.
Andere namen:
  • HA DNA-vaccin
  • Trivalent DNA-vaccin tegen seizoensgriep
  • VRC-FLUDNA061-00-VP
Placebo-vergelijker: Group 1B (18-50 yrs): TIV only
Phosphate buffered saline (PBS) on Day 0 + TIV at Week 36
2012/13 Seizoensinfluenza trivalent geïnactiveerd vaccin (TIV)
Andere namen:
  • Trivalent Inactivated Vaccine
Placebo-vergelijker: Group 2B (51-70 yrs): TIV only
Phosphate buffered saline (PBS) on Day 0 + TIV at Week 36
2012/13 Seizoensinfluenza trivalent geïnactiveerd vaccin (TIV)
Andere namen:
  • Trivalent Inactivated Vaccine

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Frequency of subjects per Group of serious adverse events (SAEs)
Tijdsspanne: Day 0 (after injection) to Week 60 (Visit 07)
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
Tijdsspanne: Within 7 days after first vaccination
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
Tijdsspanne: Within 7 days 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
Tijdsspanne: Within 7 days 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
Tijdsspanne: Within 7 days 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.
Tijdsspanne: Through Day 28 after first 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.
Tijdsspanne: Through Day 28 after second vaccincation
Frequency of unsolicited adverse events (AEs) during 28 days after TIV vaccination by group.
Through Day 28 after second vaccincation

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
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.
Tijdsspanne: Week 40 (4 weeks after TIV)
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.
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
Tijdsspanne: Week 40 (4 weeks after TIV)
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.
Week 40 (4 weeks after TIV)

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Onderzoekers

  • Studie directeur: Barney S Graham, M.D., Ph.D., Chief, Clinical Trials Core Vaccine Research Center, NIAID, NIH
  • Studie stoel: Julie Ledgerwood, D.O., Deputy Chief, Clinical Trials Core Vaccine Research Center, NIAID, NIH

Publicaties en nuttige links

De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start

1 december 2011

Primaire voltooiing (Werkelijk)

1 april 2013

Studie voltooiing (Werkelijk)

1 april 2013

Studieregistratiedata

Eerst ingediend

21 december 2011

Eerst ingediend dat voldeed aan de QC-criteria

21 december 2011

Eerst geplaatst (Schatting)

23 december 2011

Updates van studierecords

Laatste update geplaatst (Schatting)

24 maart 2016

Laatste update ingediend die voldeed aan QC-criteria

23 maart 2016

Laatst geverifieerd

1 maart 2016

Meer informatie

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

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