Open Label Evaluation of H5N1 Vaccine at Vaccine Manufacturing Facilities
Open Label Evaluation of H5N1 Vaccine at Vaccine Manufacturing Facilities
The purpose of this research is to study side effects and safety of a new H5N1 flu (bird flu)
 vaccine and to look at how well people's immune systems make antibodies to fight infection
 after they get the vaccine. Up to 300 healthy people who are working at Aventis Pasteur H5N1
 virus vaccine production facility in Swiftwater, PA, during the flu season are being asked to
 participate. It is important for vaccine production workers to receive the vaccine in order
 to minimize the risk of this bird flu virus combining with the regular flu virus. Volunteers
 in this study will have a medical screening, 2 vaccinations a month apart, 2 blood sample
 collections (1 before and 1 after the vaccinations to compare), 5 clinic visits, and
 follow-up over 6 months. They will also complete a diary card and to write down their
 temperature once a day and any symptoms they have every day during the week after they get
 their second shot. They will also be asked to write down any drugs or medicines they take.
The primary goal of this phase I/II, single center, open label study is to obtain additional
 safety and immunogenicity data on two 90 µg doses of H5N1. It is anticipated that this dose
 level will result in an acceptable proportion of subjects achieving a potentially protective
 postvaccination antibody titer combined with an acceptable safety profile. The purpose of the
 current study is to induce maximal anti-H5N1 titers as quickly as possible in order to
 protect at-risk personnel manufacturing a commercial-scale H5N1 vaccine under contract to the
 United States government. The study will be performed under the direction of investigators at
 the University of Maryland School of Medicine's Center for Vaccine Development. Volunteers
 will be enrolled, vaccinated, and followed at Sanofi Pasteur, in Swiftwater, PA. Up to 300
 healthy vaccine production worker volunteers, aged 18 years and older, will receive 90 mcg of
 the influenza A/H5N1 vaccine by intramuscular injection. Volunteers will receive 2 doses of
 the vaccine separated by approximately 28 days. Serum HAI and neutralizing antibody titers
 will be assessed approximately 1 month after the second vaccine dose. Volunteers will be
 observed in the clinic for at least 15 minutes after each vaccination, and they will maintain
 a memory aid to record oral temperature and systemic and local adverse events (AEs) for seven
 days after each immunization. Volunteers will return to the clinic 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 (Day 0) and on Day 56. Primary study objectives are to: (1) determine the safety
 of subvirion inactivated A/H5N1 vaccine in healthy vaccine production workers adults; and (2)
 determine the immunogenicity of subvirion inactivated H5N1 vaccine in healthy adults
 approximately 1 month following receipt of two 90 mcg doses of vaccine. Primary study
 endpoints are: (1) adverse event (AE) or serious adverse event information (solicited
 in-clinic and via memory aids, concomitant medications, and periodic targeted physical
 assessment); (2) geometric mean titer (GMT) and frequency of 4-fold or greater increases in
 neutralizing antibody titers at two months after receipt of the first dose of vaccine; (3)
 GMT and frequency of 4-fold or greater increases in serum hemagglutination inhibition (HAI)
 antibody titers at 2 months after receipt of the first dose of vaccine; and (4) proportion of
 subjects achieving a serum neutralizing antibody titer of 1:40 against the influenza A/H5N1
 virus 28 days after receipt of the second dose of vaccine (approximately Day 56).
Inclusion Criteria:

 1. Working in the production of H5N1 vaccine at Aventis Pasteur facilities at Swiftwater,
 Pennsylvania.

 2. Male or nonpregnant female (as indicated by a negative urine pregnancy test prior to
 each dose of vaccine), aged 18 years and older.

 3. 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.

 4. Is in good health, as determined by vital signs (pulse, blood pressure, oral
 temperature), medical history, and a targeted physical examination based on medical
 history.

 5. Able to understand and comply with planned study procedures.

 6. Provides informed consent prior to any study procedures and is available for all study
 visits.

 Exclusion Criteria:

 1. Has a known allergy to eggs or other components of the vaccine.

 2. Has a known allergy or sensitivity to latex (in the stopper).

 3. Is breastfeeding.

 4. Is undergoing immunosuppression as a result of an underlying illness or treatment.

 5. Has an active neoplastic disease or a history of any hematologic malignancy.

 6. Is using oral or parenteral steroids, high-dose inhaled steroids (>800 mcg/day of
 beclomethasone dipropionate or equivalent) or other immunosuppressive or cytotoxic
 drugs.

 7. Has a history of receiving immunoglobulin or other blood product within the 3 months
 prior to enrollment in this study.

 8. Has an acute illness, including an oral temperature greater than 100.4 degrees F,
 within 1 week of vaccination.

 9. 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 6-month study period.

 10. 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.