| Study summary: |
|
Recently, a novel swine-origin influenza A/H1N1 virus was identified as a significant cause
of febrile respiratory illnesses in Mexico and the United States. It rapidly spread
prompting the World Health Organization to declare a pandemic. Data from several cohorts in
different age groups that received licensed trivalent seasonal influenza vaccines suggest
that these vaccines are unlikely to provide protection against the new virus. These data
indicate the need to develop vaccines against the new H1N1 strain and suggest that different
vaccine strategies (e.g., number of doses, need for adjuvant) may be appropriate for persons
in different age groups. Based on clinical data from the clinical trials with vaccines
containing novel influenza A antigens, a higher dosage, or multiple doses of a novel antigen
may be necessary to generate potentially protective antibody responses. Alternatively,
inactivated influenza H1N1 vaccines administered with adjuvants, such as AS03, may confer
protection to a maximal number of vaccine recipients. This protocol will explore antibody
responses following vaccination with an inactivated influenza H1N1 virus vaccine at 3
different dose levels combined with AS03 adjuvant and at 2 different dose levels
administered without adjuvant. This study will assess the immune response following a single
dose of vaccine with or without AS03 adjuvant, to assess whether individuals have any
pre-existing 'prime' immunity, such that the initial H1N1 vaccination serves as a boost,
thus conferring a more rapid time to protection with the need for fewer doses. Antibody
responses will be assessed 8 days after each dose to evaluate the development of an
anamnestic response. In addition, antibody responses will be assessed 21 days after each
dose. The primary objectives are: safety, to assess the safety of inactivated H1N1 vaccine
when administered at 3.75, 7.5 or 15 mcg combined with AS03 adjuvant and at 7.5 or 15 mcg
administered without adjuvant; and immunogenicity, to assess the antibody response at Day 21
following a single dose of inactivated H1N1 vaccine when administered at 3.75, 7.5 or 15 mcg
combined with AS03 adjuvant and at 7.5 or 15 mcg administered without adjuvant, stratified
by age of recipient. The secondary objective is immunogenicity, to assess the antibody
response following 2 doses of inactivated H1N1 vaccine when administered at 3.75, 7.5 or 15
mcg combined with AS03 adjuvant and at 7.5 or 15 mcg administered without adjuvant,
stratified by age of recipient. Participants will include up to 800 healthy adults who have
no history of novel influenza H1N1 2009 infection or novel influenza H1N1 2009 vaccination.
This is a randomized, double-blinded, Phase II study. Subjects will be randomized into 5
groups, stratified by age (150 subjects per dose group with 100 subjects in the 18-64 years
of age stratum and 50 subjects in the greater than or equal to 65 years of age stratum), to
receive intramuscular inactivated influenza H1N1 vaccine at 3.75, 7.5 or 15 mcg combined
with AS03 adjuvant (Groups 1, 2, and 3, respectively) or at 7.5 or 15 mcg without adjuvant
(Groups 4 and 5, respectively). The vaccine, with and without adjuvant, will be administered
at Days 0 and 21. Following immunization, safety will be measured by assessment of adverse
events (AEs) through 21 days following the last vaccination (Day 42 for those receiving both
doses and Day 21 for those who do not receive the second dose), serious adverse events
(SAEs) and new-onset chronic medical conditions through 12 months post final vaccination
(Day 365 after second vaccination), and reactogenicity to the vaccine for 8 days following
each vaccination (Day 0-7). Immunogenicity testing will include hemagglutination inhibition
assay (HAI) and neutralizing antibody testing on serum obtained prior to each vaccination,
8-10 days after each vaccination, 21 days (Day 42), 6 months (Day 201) and 12 months (Day
386) following the second vaccination. |
| Criteria: |
|
Inclusion Criteria:
- Are males or non-pregnant females age 18 and older, inclusive.
- Women of child-bearing potential (not surgically sterile via tubal ligation,
bilateral oophorectomy or hysterectomy or who are not postmenopausal for greater than
or equal to 1 year) must agree to practice adequate contraception that may include,
but is not limited to, abstinence, monogamous relationship with vasectomized partner,
barrier methods such as condoms, diaphragms, spermicides, intrauterine devices, and
licensed hormonal methods during the study for at least 30 days following the last
vaccination.
- Are in good health, as determined by vital signs, medical history to ensure any
existing medical diagnoses or conditions are stable and not considered clinically
significant, and limited physical examination. A stable chronic medical condition is
defined as no 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 that is done for financial reasons,
as long as in the same class of medication will not be considered a violation of this
inclusion criterion. Any change in prescription medication due to improvement of a
disease outcome will not be considered a violation of this inclusion criterion.
- Have erythrocyte sedimentation rate (ESR) less than 30 mm per hour.
- Are able to understand and comply with planned study procedures.
- Provide written informed consent prior to initiation of any study procedures.
Exclusion Criteria:
- Have a known allergy to eggs or other components of the vaccine (including squalene
based adjuvants, thimerosal, neomycin, polymyxin, and chicken protein).
- Have a positive urine or serum pregnancy test within 24 hours prior to vaccination if
female of childbearing potential or women who are breastfeeding.
- Have immunosuppression as a result of an underlying illness or treatment, or use of
anticancer chemotherapy or radiation therapy (cytotoxic) within the preceding 36
months.
- Have an active neoplastic disease or a history of any hematologic malignancy.
- Have long term use of glucocorticoids including oral, parenteral or high-dose inhaled
steroids (>800 micrograms (mcg)/day of beclomethasone dipropionate or equivalent)
within the preceding 6 months. (Nasal and topical steroids are allowed.)
- Have a diagnosis of schizophrenia, bipolar disease, or other major psychiatric
diagnosis.
- Have been hospitalized for psychiatric illness, history of suicide attempt, or
confinement for danger to self or others, within the past 10 years.
- Are receiving psychiatric drugs (aripiprazole, clozapine, ziprasidone, haloperidol,
molindone, loxapine, thioridazine, thiothixene, pimozide, fluphenazine, risperidone,
mesoridazine, quetiapine, trifluoperazine, chlorprothixene, chlorpromazine,
perphenazine, trifluopromazine, 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
de-compensating symptoms will be allowed to be enrolled in the study.
- Have a history of receiving immunoglobulin or other blood product within the 3 months
prior to vaccination in this study.
- 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 this study (prior to the Day 386 clinic visit - 365 days
after the second vaccination).
- Have received any live licensed vaccines within 4 weeks or inactivated licensed
vaccines within 2 weeks prior to vaccination in this study or plan receipt of such
vaccines within 21 days following the second vaccination. This is inclusive of
seasonal influenza vaccines.
- 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.
- Have a history of severe reactions following previous immunization with influenza
virus vaccines.
- Have an acute illness, including an oral temperature greater than 100.4 degrees
Fahrenheit, within 3 days prior to vaccination.
- Have any condition that would, in the opinion of the site investigator, place them at
an unacceptable risk of injury or render them unable to meet the requirements of the
protocol.
- Participated in a novel influenza H1N1 2009 vaccine study in the past 2 years or have
a history of novel influenza H1N1 2009 infection prior to enrollment.
- Have known active human immunodeficiency virus (HIV), Hepatitis B, or Hepatitis C
infection or autoimmune hepatitis.
- Have a history of alcohol or drug abuse in the last 5 years.
- Plan to travel outside of North America in the time between the first vaccination and
42 days following the first vaccination.
- Have a history of Guillain-Barré Syndrome.
- Have any condition that the investigator believes may interfere with successful
completion of the study. |