The purposes of this study are:

• To determine the dose-related safety of flu vaccine in healthy adults;
• To determine the dose-related effectiveness of flu vaccine in healthy adults approximately 1 month following receipt of 2 doses of vaccine;
• To provide information for the selection of the best dose levels of vaccine for further studies.

Condition	Intervention	Phase
Influenza	Vaccine: Influenza A/H5N1 Vaccine	Phase I Phase II

Further Study Details: 

Expected Total Enrollment:  450

Approximately 450 healthy adults, 18 to 64 years old, inclusive, will be enrolled into this multicenter, randomized, double-blinded, placebo-controlled, dose-ranging clinical trial. The study will be conducted in 2 stages. During Stage I, 113 subjects who meet the entry criteria for the study will be randomized to receive saline placebo, or 7.5, 15, 45, or 90 µg of the influenza A/H5N1 vaccine by intramuscular injection in an approximate 1:2:2:2:2 ratio (N=25/vaccine dose group and 13 in the placebo group). Subjects will receive 2 doses separated by approximately 28 days. Vaccine administration will be performed by an unblinded vaccine administrator, who will not be involved in subsequent assessments. Subjects will be observed in the clinic for 15 to 30 minutes after inoculation, and subjects will maintain a memory aid to record oral temperature and systemic and local adverse events (AEs) for 7 days after each immunization. Subjects will be contacted by telephone on Day 2 after each immunization to assess for the occurrence of AEs, and they will return on Day 7 for AE and concomitant medication assessment, a targeted physical examination (if indicated), and review of the memory aid. Serum for immunogenicity evaluations will be obtained prior to the first vaccination (ie, at Screening for Stage I and Day 0 for Stage II), prior to the second vaccination, at Day 28, and on Days 56 and 208. All available 7-day safety data following the first dose of vaccine on the 113 subjects enrolled in Stage I will be reviewed by the Data and Safety Monitoring Board (DSMB) prior to enrollment of the remaining subjects (Stage II), who will be followed according to the same protocol. All available 7-day safety data following the second dose of vaccine on the subjects enrolled in Stage I also will be reviewed by the DSMB prior to administering the second dose of vaccine to the subjects in Stage II.

Ages Eligible for Study:  18 Years   -   64 Years,  Genders Eligible for Study:  Both

Accepts Healthy Volunteers

Criteria

Inclusion Criteria:

Subjects must meet all of the following inclusion criteria to participate in this study:

• Male or nonpregnant female (as indicated by a negative urine pregnancy test immediately prior to vaccine administration) between the ages of 18 and 64 years, inclusive.
• Women of childbearing potential who are at risk of becoming pregnant must agree to practice adequate contraception (ie, barrier method, abstinence, and licensed hormonal methods) for the entire study period.
• Is in good health, as determined by vital signs (heart rate, blood pressure, oral temperature), medical history and a targeted physical examination based on medical history.
• In Stage I subjects, should have normal laboratory values of Hgb, WBC, Plt, ALT, and creatinine prior to the first immunization.
• Able to understand and comply with planned study procedures.
• Provides informed consent prior to any study procedures and is available for all study visits.

Exclusion Criteria:

Subjects who meet any of the following exclusion criteria at baseline will be excluded from study participation:

• Has a known allergy to eggs or other components of the vaccine.
• Has a positive urine pregnancy test prior to vaccination (if female of childbearing potential) or women who are breastfeeding.
• Is undergoing immunosuppression as a result of an underlying illness or treatment.
• Has an active neoplastic disease or a history of any hematologic malignancy.
• Is using oral or parenteral steroids, high-dose inhaled steroids (>800 µg/day of beclomethasone dipropionate or equivalent) or other immunosuppressive or cytotoxic drugs.
• Has a history of receiving immunoglobulin or other blood product 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.
• Has an acute or chronic medical condition that, in the opinion of the investigator, would render vaccination unsafe or would interfere with the evaluation of responses (this includes, but is not limited to: known chronic liver disease, significant renal disease, unstable or progressive neurological disorders, diabetes mellitus, and transplant recipients).
• Has a history of severe reactions following immunization with contemporary influenza virus vaccines.
• Has an acute illness, including an oral temperature greater than 100.4ºF, within 1 week of vaccination.
• 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 7-month study period.
• Has any condition that would, in the opinion of the site investigator, place the subject at an unacceptable risk of injury or render the subject unable to meet the requirements of the protocol.

California
      UCLA Center For Vaccine Research, Torrance,  California,  90502,  United States
Maryland
      University of Maryland School of Medicine, Baltimore,  Maryland,  21201,  United States
New York
      University of Rochester - Rochester NY (VTEU), Rochester,  New York,  14642,  United States
      University of Rochester School of Medicine and Dentistry, Rochester,  New York,  14642,  United States
      University of Rochester Med. Ctr., Rochester,  New York,  14642,  United States

Study ID Numbers:  04-063
Last Updated:  August 1, 2005
Record first received:  June 26, 2005
ClinicalTrials.gov Identifier:  NCT00115986
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-08-02