Systems Biology of Influenza A (H5N1) Virus Monovalent Vaccine With and Without Adjuvant System 03 (AS03)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Emory University
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT01910519
First received: July 23, 2013
Last updated: January 31, 2014
Last verified: January 2014
  Purpose

The influenza virus (a germ) causes influenza or "flu." The flu is an infection of the breathing tubes and the lungs. In recent years, flu viruses that at first only infected birds have begun to infect humans. One of these strains is called avian influenza (A/H5N1 subtype) or "bird flu". Although no human cases of bird flu have been diagnosed in the United States, this strain has caused severe illness and death in several hundred people since late 2003. .

Vaccination is the most effective way of controlling flu and preventing its illness and complications. Vaccines help prevent illness by causing the body to make antibodies that fight infection. One way to improve the effectiveness of a vaccine is to include a substance that can stimulate the immune system to make more antibodies. This type of substance is called an adjuvant; one type of adjuvant is called AS03 (Adjuvant System 03).

This study will compare the different immune responses to Influenza A (H5N1) Virus Monovalent Vaccine with and without the AS03 adjuvant. The Influenza A (H5N1) Virus Monovalent Vaccine with AS03 adjuvant vaccine is approved for use for adults to protect against flu caused by the A/H5N1 "bird flu" virus in Europe but none of the vaccines to be used in the study are approved for use in the United States. The results of this study will help researchers learn about better ways to vaccinate people against the H5N1 flu.


Condition Intervention Phase
Influenza A Virus, H5N1 Subtype
Biological: Influenza A (H5N1) Virus Monovalent Vaccine with AS03 adjuvant
Biological: Influenza A (H5N1) Virus Monovalent Vaccine without AS03 adjuvant
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Systems Biology of Influenza A (H5N1) Virus Monovalent Vaccine With and Without AS03 Adjuvant (HIPC: VAX-010)

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Change in traditional immune parameters measurements using Luminex assays and gene expression measurement using microarray expriments from baseline with Influenza A Vaccine with and without AS03 adjuvant. [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    To identify innate immune signatures; 1 day post first vaccination

  • Change in traditional immune parameters measurements using Luminex assays and gene expression measurement using microarray expriments from baseline with Influenza A Vaccine with and without AS03 adjuvant. [ Time Frame: Day 3 ] [ Designated as safety issue: No ]
    To identify innate immune signatures; 3 days post first vaccination

  • Change in traditional immune parameters measurements using Luminex assays and gene expression measurement using microarray expriments from baseline with Influenza A Vaccine with and without AS03 adjuvant. [ Time Frame: Day 7 ] [ Designated as safety issue: No ]
    To identify innate immune signatures; 7 days post first vaccination

  • Change in traditional immune parameters measurements using Luminex assays and gene expression measurement using microarray expriments from baseline with Influenza A Vaccine with and without AS03 adjuvant. [ Time Frame: Day 22 ] [ Designated as safety issue: No ]
    To identify innate immune signatures; 1 day post second vaccination

  • Change in traditional immune parameters measurements using Luminex assays and gene expression measurement using microarray expriments from baseline with Influenza A Vaccine with and without AS03 adjuvant. [ Time Frame: Day 24 ] [ Designated as safety issue: No ]
    To identify innate immune signatures; 3 days post second vaccination

  • Change in traditional immune parameters measurements using Luminex assays and gene expression measurement using microarray expriments from baseline with Influenza A Vaccine with and without AS03 adjuvant. [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
    To identify innate immune signatures; 7 days post second vaccination

  • Measurement of Hemagglutination Inhibition Assay (HAI) titers +/- microneutralization (MN) titers with Influenza A Vaccine with and without AS03 adjuvant. [ Time Frame: Day 21 ] [ Designated as safety issue: No ]
    To measure selective adaptive immune response; 21 days post first vaccination

  • Measurement of Hemagglutination Inhibition Assay (HAI) titers +/- microneutralization (MN) titers with Influenza A Vaccine with and without AS03 adjuvant. [ Time Frame: Day 42 ] [ Designated as safety issue: No ]
    To measure selective adaptive immune response; 21 days post second vaccination

  • Correlation of innate immune signatures and adaptive immune responses using correlation coefficient and SAM with quantitative outcome. [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    1 day post first vaccination

  • Correlation of innate immune signatures and adaptive immune responses using correlation coefficient and SAM with quantitative outcome. [ Time Frame: Day 3 ] [ Designated as safety issue: No ]
    3 days post first vaccination

  • Correlation of innate immune signatures and adaptive immune responses using correlation coefficient and SAM with quantitative outcome. [ Time Frame: Day 7 ] [ Designated as safety issue: No ]
    7 days post first vaccination

  • Correlation of innate immune signatures and adaptive immune responses using correlation coefficient and SAM with quantitative outcome. [ Time Frame: Day 22 ] [ Designated as safety issue: No ]
    1 day post second vaccination

  • Correlation of innate immune signatures and adaptive immune responses using correlation coefficient and SAM with quantitative outcome. [ Time Frame: Day 24 ] [ Designated as safety issue: No ]
    3 days post second vaccination

  • Correlation of innate immune signatures and adaptive immune responses using correlation coefficient and SAM with quantitative outcome. [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
    7 days post second vaccination


Secondary Outcome Measures:
  • Frequency, severity and causality of all adverse events in participant recieving Influenza A Vaccine with and without AS03 adjuvant [ Time Frame: Day 400 ] [ Designated as safety issue: No ]

Enrollment: 50
Study Start Date: July 2013
Estimated Study Completion Date: May 2015
Estimated Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Influenza A Vaccine with AS03 adjuvant
Subjects will receive 2 intramuscular doses of Influenza A (H5N1) Virus Monovalent Vaccine with AS03 adjuvant given 21 days apart
Biological: Influenza A (H5N1) Virus Monovalent Vaccine with AS03 adjuvant
Other Names:
  • Q-Pan
  • Q-Pan H5N1
  • adjuvanted Q-Pan H5N1
Experimental: Influenza A Vaccine without AS03 adjuvant
Subjects will receive 2 intramuscular doses of Influenza A (H5N1) Virus Monovalent Vaccine without AS03 adjuvant given 21 days apart
Biological: Influenza A (H5N1) Virus Monovalent Vaccine without AS03 adjuvant

  Eligibility

Ages Eligible for Study:   21 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Individuals in good health (as determined by vital signs, medical history, physical examination and laboratory tests).
  • Able to understand and give informed consent.
  • Women of childbearing potential must agree to practice adequate contraception 1 months prior to study entry and until day 100 of the study.

Exclusion Criteria:

  • Personal or family history of sleeping disorders including any of the following: Narcolepsy with or without cataplexy; Idiopathic Hypersomnia or excessive daytime sleepiness of unknown origin; Sleep paralysis; Sleep related hallucinations (hypnagogic or hypnopompic hallucinations)
  • Human leukocyte antigen (HLA)-DQB1*06:02 positivity ( or DQB1*06 positivity if high resolution HLA testing cannot be performed)
  • An abnormal erythrocyte sedimentation rate at baseline
  • Receipt of blood products 3 months prior to study entry and until day 100 of the study.
  • Volunteers who donated blood 56 days before screening and have plans to donate on or before day 100 of the study
  • Hemoglobin value of less than 12 mg/dL for females and less than 13 mg/dL for males.
  • A positive result in the Narcolepsy Mini Screen questionnaire.
  • A score of equal or greater to 11 on the Epworth sleepiness scale questionnaire.
  • Receipt of any experimental agents within 6 weeks prior to first vaccination and until the completion of the study.
  • Receipt of any licensed live vaccine within 4 weeks or any licensed inactivated vaccine within 2 weeks prior to the first study vaccination or planned receipt of any vaccine within 42 days after study entry.
  • Receipt of a H5 vaccine or AS03-adjuvanted vaccine at any time in the past prior to current study or have a history of A/H5N1 infection.
  • Influenza-like illness (ILI) or documented influenza infection during the 2013-2014 influenza season. [Not excluded from the study, volunteers with prior upper respiratory infections other than ILI].
  • Chronic medical problems including (but not limited to) insulin dependent diabetes, severe heart disease, severe lung disease, severe liver disease, severe kidney disease, autoimmune disease, severe gastrointestinal disease.
  • Alcohol or drug abuse and psychiatric conditions that in the opinion of the investigator would preclude compliance with the trial or interpretation of safety or endpoint data.
  • Impaired immune function or chronic infections including (but not limited to) HIV, hepatitis B or C; organ transplant; active cancer or any history of hematologic cancer; receipt of chemotherapy, radiation therapy (past 36 months) or any other potentially immunosuppressive therapy [i.e. Systemic steroids at any dose and intra-articular administration of steroids in the past 3 months; (Nasal and topical steroids are allowed)], congenital immunodeficiency, anatomical or functional asplenia.
  • Heart rate less than 40 bpm or greater than 100 bpm. Systolic blood pressure is less than 90 mm Hg or equal or greater than 160 mm Hg. Diastolic blood pressure is less than 60 mm Hg or equal or greater than 100 mg Hg.
  • Pregnancy or postpartum (less than 1 year after delivery) or breast feeding
  • Severe reactions to prior vaccination with influenza virus vaccines, including anaphylaxis.
  • History of Guillain Barré syndrome
  • A previous sudden life-threatening allergic reaction to any ingredient of Influenza A (H5N1) Virus Monovalent Vaccine with or without AS03 adjuvant or to any of the substances that may be present in trace amounts such as thiomersal, egg residues including ovalbumin as well as residual amounts of sodium deoxycholate detergent, formaldehyde and sucrose.
  • Volunteers with any acute illness, including any fever (> 100.4 F [> 38.0C], regardless of the route) within 3 days prior to study entry.
  • Social, occupational, or any other condition that in the opinion of the investigator might interfere with compliance with the study and vaccine evaluation.
  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: NCT01910519

Locations
United States, Georgia
The Hope Clinic - Emory Vaccine Center
Decatur, Georgia, United States, 30030
Sponsors and Collaborators
Emory University
Investigators
Principal Investigator: Nadine Rouphael, MD Hope Clinic, Emory University
  More Information

Additional Information:
No publications provided

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT01910519     History of Changes
Other Study ID Numbers: DAIT HIPC: VAX-010
Study First Received: July 23, 2013
Last Updated: January 31, 2014
Health Authority: United States: Data and Safety Monitoring Board
United States: Federal Government
United States: Food and Drug Administration
United States: Institutional Review Board

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

ClinicalTrials.gov processed this record on October 01, 2014