| Study summary: |
|
Severe disease in humans due to avian influenza viruses of the H5N1 subtype has raised
considerable concern regarding the potential emergence of these viruses in pandemic form.
Planning for control of such pandemics is of vital importance, and a cornerstone of this
planning is the development of effective vaccines for H5N1. This study is designed to gather
critical information on the safety, tolerability, and immunogenicity of booster vaccination
with influenza A/Anhui/05 with and without the adjuvant MF59 in subjects previously primed
with the clade 1 vaccine or unprimed individuals. Primary objectives are: to evaluate
booster vaccination with a different variant/clade of A/Anhui/05 vaccine to assess possible
prime for a broad immune response by 1 or 2 previous doses of A/Vietnam/1203/04; to compare
1-dose versus 2-dose priming of A/Vietnam/1203/04 followed by heterologous boosting with
A/Anhui/05; to assess the safety of MF59 adjuvanted A/Anhui/05 vaccine in primed subjects;
and to compare safety and immunogenicity of 1 and 2 doses of A/Anhui/05 with or without MF59
adjuvant, or to saline placebo, in a Phase I dose response study in naïve subjects. Up to
180 healthy adult subjects aged 18 through 49 (Subjects previously enrolled in 07-0019 will
be eligible for 08-0013 even if they are older than 49 years of age at the time of
enrollment into 08-0013.) who were previously enrolled in Division of Microbiology and
Infectious Diseases (DMID) 07-0019 and received either 1 or 2 priming doses of
A/Vietnam/1203/04 H5 influenza vaccine will be enrolled in this study. Additionally,
approximately 555 healthy adult subjects aged 18 through 49 H5 vaccine naïve will be
recruited to receive 2 doses, 28 days apart, of A/Anhui/05 vaccine with or without MF59
adjuvant or placebo. Entry criteria for the newly enrolled subjects will be the same as
those used in DMID 07-0019. Because extensive safety data were collected for similar H5
vaccines, subjects will not be screened with clinical laboratory tests. The booster for
Groups 8-9 will be randomized to 1 of 2 possible doses, with approximately 20 subjects per
Group (allocation ratio 1:1) in each dose assignment: 3.75 micrograms (mcg) MF59, or 3.75
mcg. Newly enrolled, vaccine naïve subjects in Group 10 will be randomized to 1 of 9
possible dosages with or without MF59 adjuvant, with approximately 50 subjects in each
dosage assignment: 3.75 mcg MF59, 3.75 mcg, 7.5 mcg MF59, 7.5 mcg, 15.0 mcg MF59, 15.0 mcg,
45.0 mcg MF59, 45.0 mcg, 90 mcg, or saline placebo with 3 groups of 35 subjects each,
receiving different volumes of: one injection of 0.5 mL, one injection of 0.75 mL or 2
injections of 0.75 mL, for comparison. Volunteers will be observed in the clinic for at
least 20 minutes after vaccination, and will maintain a Memory Aid to record oral
temperature and systemic and local adverse events (AEs) and serious adverse events (SAEs)
for 8 days after vaccination. Volunteers will be contacted by telephone 1 to 3 days after
vaccination (approximately Day 2 post dose) to assess for the occurrence of AEs/SAEs, and
they will return to the clinic 7 to 9 days after vaccination for AE/SAE and concomitant
medication assessment, a targeted physical examination (if indicated), and review of the
Memory Aid. Volunteers in Group 10 will return to clinic on Day 28 for review of eligibility
criteria to receive Dose Number 2 of A/Anhui/05 or placebo. Volunteers in this group will
then follow the same study schedule as following the first vaccination. All subjects will
continue to be followed for 12 months after the last vaccination. It is anticipated that
this study will enroll up to 735 subjects over 10-14 weeks. This study is linked to DMID
protocol 07-0019. |
| Criteria: |
|
Inclusion Criteria:
- Men and women, 18 through 49 (Subjects previously enrolled in 07-0019 will be
eligible for 08-0013 even if they are older than 49 years of age at the time of
enrollment into 08-0013.) years old, who either were previously enrolled and received
all scheduled vaccinations in Groups 8 and 9 under Division of Microbiology and
Infectious Diseases (DMID) 07-0019, or are new subjects who deny exposure to H5 virus
or participation in an H5 vaccine study.
- In good health, as determined by vital signs (heart rate <100 beats per minute (bpm);
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 <100.0 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 have a
history of practicing 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) in the 30 days prior to enrollment, and must agree to practice
adequate contraception 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 (other than vaccination in Protocol 07-0019).
- Has a known allergy to egg proteins (egg or egg products), or other components of the
vaccine (including thimerosal, polymyxin, neomycin, beta propiolactone, or
nonylphenol ethoxylate).
- 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. An 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 (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 lithium citrate). 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. |