Sanofi H1N1 Influenza Vaccine Administered at Different Dose Levels With and Without AS03 Adjuvant in Healthy Adult and Elderly Populations
Sanofi H1N1 Influenza Vaccine Administered at Different Dose Levels With and Without AS03 Adjuvant in Healthy Adult and Elderly Populations
The purpose of this study is to see how the body reacts to different strengths of the H1N1
 flu shot when it is given with or without an "adjuvant." An adjuvant is a substance that may
 cause the body to produce more antibodies when it is given with a vaccine. This study will
 also compare how age affects the body's response to the H1N1 flu shot. In this study, 3
 strengths of the H1N1 flu shot will be tested combined with an adjuvant. In addition, 2
 strengths of the H1N1 flu shot will be tested without adjuvant. Two H1N1 flu shots of the
 same strength, with or without adjuvant, will be given about 3 weeks apart. Participants will
 include up to 800 healthy adults, approximately 500 individuals ages 18-64 and 250
 individuals greater than or equal to age 65. Study procedures include: physical exam, blood
 samples, completing a memory aid to record vaccine side effects, medications and daily oral
 temperature. Participants will be involved in study related procedures for up to 13 months.
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 to many
 countries around the world, prompting the World Health Organization to declare a pandemic on
 June 11, 2009. 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. Adults are more likely to have measurable levels of serum
 hemagglutination inhibition assay (HAI) or neutralizing antibody than are children. 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. 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 at 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 the 3.75 micrograms (mcg),
 7.5 mcg, or 15 mcg dose combined with AS03 adjuvant and at the 7.5 mcg or 15 mcg dose
 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 mcg, 7.5 mcg,
 or 15 mcg dose combined with AS03 adjuvant and at the 7.5 mcg or 15 mcg dose 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 the 3.75 mcg, 7.5 mcg, or 15 mcg dose combined with AS03 adjuvant and at the
 7.5 mcg or 15 mcg dose 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 mcg, 7.5 mcg, or 15 mcg combined with AS03
 adjuvant (Groups 1, 2, and 3, respectively) or at 7.5 mcg or 15 mcg without adjuvant (Groups
 4 and 5, respectively). The vaccine, with and without adjuvant, will be administered at Day 0
 and Day 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 vaccine for 8 days (Day 0-7) following each
 vaccination. Immunogenicity testing will include HAI and neutralizing antibody.
Inclusion Criteria:

 1. Are males or non-pregnant females age 18 and older, inclusive.

 2. 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.

 3. 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.

 4. Have alanine aminotransferase (ALT) within normal range per local or site laboratory
 reference ranges.

 5. Are able to understand and comply with planned study procedures.

 6. Provide written informed consent prior to initiation of any study procedures.

 Exclusion Criteria:

 1. Have a known allergy to eggs or other components of the vaccine (including squalene
 based adjuvants, gelatin, formaldehyde, octoxinol, thimerosal, and chicken protein).

 2. Have a positive urine or serum pregnancy test within 24 hours prior to vaccination (if
 female of childbearing potential), or women who are breastfeeding.

 3. 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.

 4. Have an active neoplastic disease or a history of any hematologic malignancy.

 5. Have long term use of glucocorticoids including oral, parenteral or high-dose inhaled
 steroids (>800 mcg/day of beclomethasone dipropionate or equivalent) within the
 preceding 6 months. (Nasal and topical steroids are allowed.)

 6. Have a diagnosis of schizophrenia, bipolar disease, or other major psychiatric
 diagnosis.

 7. Have been hospitalized for psychiatric illness, history of suicide attempt, or
 confinement for danger to self or others, within the past 10 years.

 8. 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.

 9. Have a history of receiving immunoglobulin or other blood product within the 3 months
 prior to vaccination in this study.

 10. 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).

 11. 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.

 12. 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.

 13. Have a history of severe reactions following previous immunization with influenza
 virus vaccines.

 14. Have an acute illness, including an oral temperature greater than 100.4 degrees
 Fahrenheit, within 3 days prior to vaccination.

 15. 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.

 16. 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.

 17. Have known active human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C
 infection or autoimmune hepatitis.

 18. Have a history of alcohol or drug abuse in the last 5 years.

 19. Plan to travel outside of North America in the time between the first vaccination and
 42 days following the first vaccination.

 20. Have a history of Guillain-Barré Syndrome.

 21. Have any condition that the investigator believes may interfere with successful
 completion of the study.