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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.

Studieoversigt

Status

Afsluttet

Betingelser

Detaljeret beskrivelse

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.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

131

Fase

  • Fase 1

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

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

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år til 70 år (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ja

Køn, der er berettiget til at studere

Alle

Beskrivelse

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

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Forebyggelse
  • Tildeling: Randomiseret
  • Interventionel model: Parallel tildeling
  • Maskning: Tredobbelt

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: 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 sæsonbestemt influenza trivalent inaktiveret vaccine (TIV)
Andre navne:
  • 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.
Andre navne:
  • HA DNA-vaccine
  • Sæsonbestemt influenza trivalent DNA-vaccine
  • VRC-FLUDNA061-00-VP
Eksperimentel: 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 sæsonbestemt influenza trivalent inaktiveret vaccine (TIV)
Andre navne:
  • 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.
Andre navne:
  • HA DNA-vaccine
  • Sæsonbestemt influenza trivalent DNA-vaccine
  • VRC-FLUDNA061-00-VP
Placebo komparator: Group 1B (18-50 yrs): TIV only
Phosphate buffered saline (PBS) on Day 0 + TIV at Week 36
2012/13 sæsonbestemt influenza trivalent inaktiveret vaccine (TIV)
Andre navne:
  • Trivalent Inactivated Vaccine
Placebo komparator: Group 2B (51-70 yrs): TIV only
Phosphate buffered saline (PBS) on Day 0 + TIV at Week 36
2012/13 sæsonbestemt influenza trivalent inaktiveret vaccine (TIV)
Andre navne:
  • Trivalent Inactivated Vaccine

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Frequency of subjects per Group of serious adverse events (SAEs)
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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.
Tidsramme: 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.
Tidsramme: 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

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
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.
Tidsramme: 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
Tidsramme: 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)

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Samarbejdspartnere

Efterforskere

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

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart

1. december 2011

Primær færdiggørelse (Faktiske)

1. april 2013

Studieafslutning (Faktiske)

1. april 2013

Datoer for studieregistrering

Først indsendt

21. december 2011

Først indsendt, der opfyldte QC-kriterier

21. december 2011

Først opslået (Skøn)

23. december 2011

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Skøn)

24. marts 2016

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

23. marts 2016

Sidst verificeret

1. marts 2016

Mere information

Begreber relateret til denne undersøgelse

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

Kliniske forsøg med Influenza

Kliniske forsøg med TIV

Abonner