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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.

Aperçu de l'étude

Statut

Complété

Les conditions

Description détaillée

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.

Type d'étude

Interventionnel

Inscription (Réel)

131

Phase

  • La phase 1

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

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

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans à 70 ans (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Oui

Sexes éligibles pour l'étude

Tout

La description

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

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: La prévention
  • Répartition: Randomisé
  • Modèle interventionnel: Affectation parallèle
  • Masquage: Tripler

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: Group 1A (18-50 yrs): DNA vaccine + TIV
HA DNA Vaccine (VRC-FLUDNA061-00-VP) at Day 0 and licensed TIV at Week 36
Vaccin trivalent inactivé (VTI) contre la grippe saisonnière 2012/13
Autres noms:
  • 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.
Autres noms:
  • Vaccin ADN HA
  • Vaccin à ADN trivalent contre la grippe saisonnière
  • VRC-FLUDNA061-00-VP
Expérimental: Group 2A (51-70 yrs): DNA vaccine + TIV
HA DNA Vaccine (VRC-FLUDNA061-00-VP) at Day 0 and licensed TIV at Week 36
Vaccin trivalent inactivé (VTI) contre la grippe saisonnière 2012/13
Autres noms:
  • 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.
Autres noms:
  • Vaccin ADN HA
  • Vaccin à ADN trivalent contre la grippe saisonnière
  • VRC-FLUDNA061-00-VP
Comparateur placebo: Group 1B (18-50 yrs): TIV only
Phosphate buffered saline (PBS) on Day 0 + TIV at Week 36
Vaccin trivalent inactivé (VTI) contre la grippe saisonnière 2012/13
Autres noms:
  • Trivalent Inactivated Vaccine
Comparateur placebo: Group 2B (51-70 yrs): TIV only
Phosphate buffered saline (PBS) on Day 0 + TIV at Week 36
Vaccin trivalent inactivé (VTI) contre la grippe saisonnière 2012/13
Autres noms:
  • Trivalent Inactivated Vaccine

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Frequency of subjects per Group of serious adverse events (SAEs)
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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.
Délai: 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.
Délai: 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

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
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.
Délai: 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
Délai: 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)

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Collaborateurs

Les enquêteurs

  • Directeur d'études: Barney S Graham, M.D., Ph.D., Chief, Clinical Trials Core Vaccine Research Center, NIAID, NIH
  • Chaise d'étude: Julie Ledgerwood, D.O., Deputy Chief, Clinical Trials Core Vaccine Research Center, NIAID, NIH

Publications et liens utiles

La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude

1 décembre 2011

Achèvement primaire (Réel)

1 avril 2013

Achèvement de l'étude (Réel)

1 avril 2013

Dates d'inscription aux études

Première soumission

21 décembre 2011

Première soumission répondant aux critères de contrôle qualité

21 décembre 2011

Première publication (Estimation)

23 décembre 2011

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Estimation)

24 mars 2016

Dernière mise à jour soumise répondant aux critères de contrôle qualité

23 mars 2016

Dernière vérification

1 mars 2016

Plus d'information

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

Essais cliniques sur Grippe

Essais cliniques sur VIT

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