The purpose of this study is to evaluate the safety, any adverse events or side effects, and
the body's immune response to an experimental flu vaccine [Inactivated Influenza A/H7N7
Vaccine] being given in increasing doses. Researchers will try to find the smallest dose of
flu vaccine needed to cause antibody responses against the flu virus in both single and
repeat doses. The study will enroll 125 healthy adults ranging in age from 18 to 40 years
old. Subjects will be given 2 doses of the vaccine 28 days apart. Study procedures will
include obtaining a medical history, physical exam, blood sample collections, and use of
patient memory aids. The volunteers will be in the study for about 7 months.
This randomized, double-blinded, placebo-controlled, dose-ranging, Phase I/II, influenza
study will compare the safety, reactogenicity, and immunogenicity of increasing doses of
monovalent subvirion influenza A/H7N7 virus vaccine administered by intramuscular (IM)
injection to healthy adults. A total of 125 healthy adults ranging from 18 to 40 years old
will be enrolled at one site for this study. The subjects will be randomized to receive
saline placebo or 7.5, 15, 45, or 90 mcg of the influenza A/H7N7 vaccine by intramuscular
(IM) injection in an approximate 1:1:1:1:1 ratio (N=25/vaccine dose group and 25 in the
placebo group). Subjects will receive 2 doses separated by approximately 28 days. Subjects
will be observed in the clinic for a minimum of 30 minutes after inoculation. All 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 1-3 days
after vaccination to assess for the occurrence of AEs, and they will return to the clinic
between Day 8 and 12 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 for subjects prior to the first vaccination, at Day 28 prior to
the second vaccination, and on Days 56 and 208. A Safety Monitoring Committee (SMC) will
review available 7 day safety data at approximately Day 20 following the first subject
vaccination before administering the second dose of vaccine to any subjects. The primary
objectives of the study will be: to determine the dose-related safety of subvirion
inactivated H7N7 vaccine in healthy adults; to determine the dose-related immunogenicity of
subvirion inactivated H7N7 vaccine in healthy adults approximately 1 month following receipt
of 2 doses of vaccine; and to provide information for the selection of the best dose levels
for further studies. The secondary objective will be to evaluate the dose-related
immunogenicity and the percent of subjects responding approximately 1 and 7 months after the
first vaccination. The primary endpoints are: adverse event (AE) or serious adverse event
(SAE) information (solicited in-clinic and via memory aids, concomitant medications, and
periodic targeted physical assessment); the proportion of subjects in each dose group
achieving a serum neutralizing antibody titer of greater than or equal to 40 against the
influenza A/H7N7 virus 28 days after receipt of the second dose of vaccine (approximately
Day 56); geometric mean titer (GMT) and frequency of 4-fold or greater increases in
neutralizing antibody titers in each group 1 month after receipt of each dose, and 7 months
after receipt of the first dose of vaccine; and GMT and frequency of 4-fold or greater
increases in serum hemagglutination inhibition (HAI) antibody titers in each group 1 month
after receipt of each dose, and 7 months after receipt of the first dose of vaccine.
Participants will be involved in study related procedures for approximately 7 months. This
study is linked to DMID protocol 07-0060.
- Male or non-pregnant female (as indicated by a negative urine pregnancy test
immediately prior to vaccine administration) between the ages of 18 and 40 years,
- Women of childbearing potential (not surgically sterile or postmenopausal for greater
than or equal to 1 year) who are at risk of becoming pregnant must agree to practice
adequate contraception (i.e., barrier method, abstinence, intrauterine devices, and
licensed hormonal methods) for the entire study period.
- Is in good health, as determined by vital signs (heart rate < 100 beats per minute,
blood pressure: systolic less than or equal to 140 mm Hg and greater than or equal to
90 mm Hg, diastolic less than or equal to 90 mm Hg; oral temperature < 100 degrees
Fahrenheit), medical history to ensure stable* medical condition and a targeted
physical examination 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
- Able to understand and comply with planned study procedures.
- Provide informed consent prior to initiation of any study procedures and are
available for all study visits.
- Have a known allergy to eggs or other components of the vaccine (including gelatin,
formaldehyde, octoxinol, aluminum hydroxide, and chicken protein).
- Have a positive urine or serum pregnancy test prior to vaccination (if female of
childbearing potential) or women who are breastfeeding.
- Have 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.
- Have an active neoplastic disease or a history of any hematologic malignancy.
- Have long-term use of oral steroids, parenteral steroids, or high-dose inhaled
steroids (>800 micrograms/day of beclomethasone dipropionate or equivalent) within
the preceding 6 months (nasal and topical steroids are allowed.)
- Have a history of receiving immunoglobulin or other blood product within the 3 months
prior to enrollment in this study.
- Have received any other licensed vaccines within 2 weeks (for inactivated vaccines)
or 4 weeks (for live vaccines) prior to vaccination in this study.
- Have 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
- Have a history of severe reactions following immunization with contemporary influenza
- Have an acute illness, including an oral temperature greater than 100.4 degrees
Fahrenheit, within 1 week of vaccination.
- Received an experimental agent (vaccine, drug, biologic, device, blood product, or
medication) within 1 month prior to vaccination in this study, or expect to receive
an experimental agent during the 7-month study period.
- Plan to enroll in another clinical trial at any time during the study period.
- Have 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.
- Have a diagnosis of schizophrenia, Bi-polar disease or other major psychiatric
- Have been hospitalized for psychiatric illness, history of suicide attempt or
confinement for danger to self or others.
- Are receiving psychiatric drugs*. Subjects who are receiving a single antidepressant
drug and stable for at least 3 months prior to enrollment, without de-compensating
symptoms will be allowed to be enrolled in the study.
* aripiprazole, clozapine, ziprasidone, haloperidol, molindone, loxapine,
thioridazine, thiothixene, pimozide, fluphenazine, risperidone, mesoridazine,
quetiapine, trifluoperazine, trifluopromazine, chlorprothixene, chlorpromazine,
perphenazine, olanzapine, carbamazepine, divalproex sodium, lithium carbonate or
- Have a known active human immunodeficiency virus, hepatitis B, or hepatitis C
- Have a history of alcohol or drug abuse in the last 5 years.
- Plan to travel outside of the USA in the time between the first vaccination and 56
days following the first vaccination.
- Have a history of Guillain-Barre syndrome.
- Have any condition that the investigator believes may interfere with successful
completion of the study.