Sanofi H1N1 + TIV - Adults and Elderly
Sanofi H1N1 + TIV - Adults and Elderly
The purpose of this study is to assess the safety and immune response (body's defense against
 disease) to an experimental H1N1 influenza vaccine against the 2009 H1N1 virus. This study
 will help determine how the H1N1 flu shot should be given with the seasonal flu shot to make
 it most effective. Participants will include up to 850 healthy adults, ages 18 and older.
 Participants will receive 2 H1N1 vaccines in addition to placebo (inactive substance) and the
 seasonal flu shot over 3 study visits about 21 days apart. Study procedures include: medical
 history, physical exam, maintaining a memory aid, and blood sample collection. Participants
 will be involved in the study for about 8 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. If the novel influenza H1N1 2009 virus continues to
 circulate, it is possible that it will co-circulate with the non-pandemic seasonal influenza
 strains. In this situation, it might be beneficial to co-administer an H1N1 vaccine
 concurrent with the seasonal inactivated influenza vaccine. This protocol explores if
 vaccination with the 2009-2010 licensed seasonal trivalent influenza vaccine (TIV) has an
 effect on antibody response to the novel influenza H1N1 2009 virus and examines if receiving
 the H1N1 vaccine either concurrent with, prior to, or following the seasonal influenza
 vaccine affects the antibody response to the seasonal influenza vaccine. This is a
 randomized, double-blinded, Phase II study in up to 850 healthy males and non-pregnant
 females, aged 18 and older. The study investigates the safety, reactogenicity, and
 immunogenicity of an inactivated influenza H1N1 virus vaccine when given concurrent with or
 sequentially with (before or after) TIV. The primary safety objective is to assess the safety
 of the unadjuvanted, inactivated H1N1 influenza vaccine when administered either concurrent
 with, prior to, or following licensed seasonal influenza vaccination. The primary
 immunogenicity objective is to assess the effect of TIV on antibody response to unadjuvanted,
 inactivated influenza H1N1 vaccine as assessed by hemagglutination inhibition assay (HAI),
 stratified by age of recipient. The secondary objective is immunogenicity, to assess the
 effect of H1N1 vaccine administration on antibody response to TIV as assessed by HAI,
 stratified by age of recipient. Subjects will be randomized into 4 groups, stratified by age
 (200 subjects per group with 100 subjects per age stratum, 18-64 or greater than or equal to
 65 years of age). Group 1 will receive two 15 microgram (mcg) doses of H1N1 vaccine at Days 0
 and 21 followed by TIV on Day 42. Group 2 will receive two 15 mcg doses of H1N1 vaccine of
 which the first dose is administered concurrently with TIV. Group 3 will receive two 15 mcg
 doses of H1N1 vaccine of which the second dose is administered concurrently with TIV. Group 4
 will receive TIV administered on Day 0 followed by two 15 mcg doses of H1N1 vaccine on Days
 21 and 42. In order to maintain the blind, subjects will also receive a placebo (normal
 saline) so that two products will be administered at both Days 0 and 21, and one product will
 be administered at Day 42 for all groups. Following immunization, safety will be measured by
 assessment of adverse events for 21 days following the last vaccination (Day 42 for those who
 do not receive the second dose), serious adverse events and new-onset chronic medical
 conditions for 8 months post the first vaccination (Day 222), and reactogenicity to the
 vaccines for 8 days following each vaccination (Day 0-7). Immunogenicity testing will include
 HAI
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 targeted physical examination based on medical history. 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.

 -  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 gelatin,
 formaldehyde, octoxinol, thimerosal 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 the study period (prior to Day 180 after the third
 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 last vaccination.

 -  Has received a licensed 2009-2010 seasonal influenza vaccine.

 -  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 two 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.

 -  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
 63 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.