H5N1 Priming and Boosting Strategies
Condition: Influenza
MeSH terms: Influenza, Human; Influenza in Birds
Intervention: A/Vietnam/1203/04; A/Indonesia/05/05
Intervention description: Inactivated subvirion influenza rg A/Vietnam/1203/04 (clade 1) x PR8 A/H5N1 vaccine; dosages 45 mcg and 90 mcg.; Inactivated subvirion influenza rg A/Indonesia/05/05 (clade 2) x PR8 A/H5N1 vaccine; dosages 45 mcg and 90 mcg.
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 505.0
Sex: All
Minimum age: 18 Years
Maximum age: 49 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: influenza, H5N1, vaccine, avian influenza, parent protocol

Summary:

      Severe disease in humans due to bird influenza viruses (H5N1) has led to concern that this
      virus may result in a widespread outbreak of bird flu. The purpose of this study is to
      evaluate the dose and dosing schedule for 2 different types of H5N1 vaccine. Participants
      will be randomly assigned to 1 of 9 possible vaccine groups. All participants will receive 2
      doses of Clade 1, Clade 2, or combination Clade 1 and 2 on Day 0. All participants will
      receive a second dose of the same vaccine or a different vaccine type on study day 7, 14, 28
      or 180. Study participants will include about 500 healthy adult subjects, ages 18-49 years
      old, who have no history of prior H5 flu exposure or vaccination. Study procedures may
      include medical history, physical exam, and blood sampling. Subject participation may last up
      to 372 days. Several DMID studies have recently evaluated H5N1 vaccines in healthy adults,
      04-063, 05-0090, 05-0015, and 05-0043.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Men and women, 18 through 49 years old, who deny exposure to H5 virus or participation
             in an H5 vaccine study.

          -  In good health, as determined by vital signs (heart rate less than 100 bpm; blood
             pressure: systolic less than or equal to 140 mm Hg; diastolic less than or equal to 90
             mm Hg; oral temperature less than 100.0 degrees Fahrenheit), medical history to ensure
             stable medical condition and a targeted physical examination, as indicated, based on
             medical history. A stable medical condition is defined as no recent change in
             prescription medication, dose, or frequency of medication in the last 3 months and
             health outcomes of the specific disease are considered to be within acceptable limits
             in the last 6 months. Any change that is due to change of health care provider,
             insurance company, etc, or is done for financial reasons, as long as in the same class
             of medication, will not be considered a violation of the inclusion criterion. Any
             change to prescription medication due to improvement of a disease outcome will not be
             considered a violation of the inclusion criterion.

          -  Women of childbearing potential (not surgically sterile or postmenopausal for greater
             than or equal to 1 year) must not be pregnant as indicated by a negative pregnancy
             test (urine or serum) within 24 hours prior to vaccine administration.

          -  Women of childbearing potential who are at risk of becoming pregnant must agree to
             practice adequate contraception (i.e., barrier methods, abstinence, monogamous
             relationship with vasectomized partner, intrauterine devices, Depo-Provera, Norplant,
             oral contraceptives, contraceptive patches or other licensed, effective methods) until
             30 days following receipt of the last dose of vaccine.

          -  Able to understand and comply with planned study procedures.

          -  Able to provide informed consent prior to initiation of any study procedures and be
             available for all study visits.

        Exclusion Criteria:

          -  Has occupational exposure to poultry, to include but is not limited to chicken,
             turkey, or duck farmer, factory worker in poultry processing plant, veterinary staff
             that handles poultry; has recreational exposure to poultry, e.g. raising poultry in
             4-H club, duck hunter that slaughters/handles the "kill" or history of previous H5N1
             vaccination or exposure.

          -  Has a known allergy to eggs, egg products or other components of the vaccine
             (including gelatin, formaldehyde, octoxinol, thimerosal and egg or chicken protein).

          -  Is female of child-bearing potential who is breastfeeding or intends to become
             pregnant during the study period up to 30 days following receipt of the last dose of
             vaccine.

          -  Has immunosuppression as a result of an underlying illness or treatment with
             immunosuppressive or cytotoxic drugs, or use of anticancer chemotherapy or radiation
             therapy within the preceding 36 months.

          -  Has an active neoplastic disease (excluding non-melanoma skin cancer or prostate
             cancer that is stable in the absence of therapy) or a history of any hematologic
             malignancy. Active neoplastic disease is defined as no neoplastic disease or treatment
             for neoplastic disease within the past 5 years.

          -  Has long-term use (greater than 2 weeks) of oral or parenteral steroids
             (glucocorticoids), or high-dose inhaled steroids (>800 mcg/day of beclomethasone
             dipropionate or equivalent) within the preceding 6 months (nasal and topical steroids
             are allowed).

          -  Has a history of receiving immunoglobulin or other blood products within the 3 months
             prior to enrollment in this study.

          -  Has received any other licensed vaccines within 2 weeks (for inactivated vaccines) or
             4 weeks (for live vaccines) prior to enrollment in this study, or plans to receive any
             other licensed vaccines within 2 weeks (for inactivated vaccines) or 4 weeks (for live
             vaccines) following each study vaccine.

          -  Has an acute or chronic medical condition that would render vaccination unsafe or
             would interfere with the evaluation of responses. This includes, but is not limited to
             solicited reactogenicity symptoms, known chronic liver disease, significant renal
             disease, unstable or progressive neurological disorders, diabetes mellitus, and
             transplant recipients.

          -  Has a history of severe reactions following vaccination with contemporary influenza
             virus vaccines.

          -  Has an acute illness or has an oral temperature greater than 99.9 degrees Fahrenheit
             (37.7 degrees Celsius) within 3 days prior to enrollment.

          -  Has received an experimental agent (vaccine, drug, biologic, device, blood product, or
             medication) within 1 month prior to enrollment in this study, or expects to receive an
             experimental agent during the study period.

          -  Has any condition that would, in the opinion of the site principal investigator place
             the subject at an unacceptable risk of injury or render the subject unable to meet the
             requirements of the protocol.

          -  Has a diagnosis of schizophrenia, bipolar disease or other severe (disabling) chronic
             psychiatric diagnosis.

          -  Has been hospitalized for psychiatric illness, history of suicide attempt or
             confinement for danger to self or others.

          -  Is receiving psychiatric drugs. Subjects who are receiving a single antidepressant
             drug and are stable for at least 3 months prior to enrollment without decompensating
             are allowed enrollment into the study.

          -  Has known human immunodeficiency virus, hepatitis B, or hepatitis C infection.

          -  Has a history of alcohol or drug abuse in the 5 years prior to enrollment.

          -  Has a history of Guillain-Barré syndrome.

          -  Has any condition that the investigator believes may interfere with successful
             completion of the study.

          -  Plans to enroll in another clinical trial (that has a study intervention in the form
             of drug, biologic or device that could interfere with safety assessment of H5N1
             vaccine) at any time during the study period.