Sanofi H1N1 + TIV - Adults and Elderly

Condition(s) targeted: Influenza

Intervention: Trivalent inactivated influenza vaccine (Biological); Inactivated H1N1 Vaccine (Biological); Placebo (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)

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.

Official title: Effect of Administration of Licensed TIV Vaccine on the Safety and Immunogenicity of an Unadjuvanted Sanofi Pasteur H1N1 Influenza Vaccine in Healthy Adult and Elderly Populations

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Primary outcome:

Number of Participants Age 18 to 64 Years With a Serum Hemagglutination Inhibition Assay (HAI) Antibody Titer of 1:40 or Greater Against the H1N1 2009 Virus 21 Days Following the First Dose of H1N1 Vaccine

Number of Participants Age 65 Years and Older With a Serum Hemagglutination Inhibition Assay (HAI) Antibody Titer of 1:40 or Greater Against the H1N1 2009 Virus 21 Days Following the First Dose of H1N1 Vaccine

Number of Participants Reporting Vaccine-associated Serious Adverse Events (SAEs)

Number of Participants Age 18 to 64 Years With 4-fold or Greater Hemagglutination Inhibition Assay (HAI) Antibody Titer Increases Against the Influenza H1N1 2009 Virus 21 Days Following the First Dose of H1N1 Vaccine

Number of Participants Age 65 Years and Older With 4-fold or Greater Hemagglutination Inhibition Assay (HAI) Antibody Titer Increases Against the Influenza H1N1 2009 Virus 21 Days Following the First Dose of H1N1 Vaccine

Number of Participants Reporting Solicited Subjective Systemic Reactions After the First Vaccination

Number of Participants Reporting Solicited Subjective Systemic Reactions After the Second Vaccination

Number of Participants Reporting Solicited Subjective Systemic Reactions After the Third Vaccination

Number of Participants Reporting Fever After the First Vaccination

Number of Participants Reporting Fever After the Second Vaccination

Number of Participants Reporting Fever After the Third Vaccination

Number of Participants Reporting Solicited Subjective Local Reactions After the First H1N1 Vaccination

Number of Participants Reporting Solicited Subjective Local Reactions After the Second H1N1 Vaccination

Number of Participants Reporting Solicited Subjective Local Reactions After the TIV Vaccination

Number of Participants Reporting Solicited Subjective Local Reactions After the First Placebo Vaccination

Number of Participants Reporting Solicited Subjective Local Reactions After the Second Placebo Vaccination

Number of Participants Reporting Solicited Quantitative Local Reactions After the First H1N1 Vaccination

Number of Participants Reporting Solicited Quantitative Local Reactions After the Second H1N1 Vaccination

Number of Participants Reporting Solicited Quantitative Local Reactions After the TIV Vaccination

Number of Participants Reporting Solicited Quantitative Local Reactions After the First Placebo Vaccination

Number of Participants Reporting Solicited Quantitative Local Reactions After the Second Placebo Vaccination

Secondary outcome:

Number of Participants Age 18 to 64 Years With 4-fold or Greater Hemagglutination Inhibition Assay (HAI) Antibody Titer Increases Against the Virus Strains in the 2009-2010 Trivalent Influenza Vaccine (TIV) 21 Days Following the Last Vaccination

Number of Participants Age 65 Years and Older With 4-fold or Greater Hemagglutination Inhibition Assay (HAI) Antibody Titer Increases Against the Virus Strains in the 2009-2010 Trivalent Influenza Vaccine (TIV) 21 Days Following the Last Vaccination

Number of Participants Age 18 to 64 Years With 4-fold or Greater Hemagglutination Inhibition Assay (HAI) Antibody Titer Increases Against the Influenza H1N1 2009 Virus 21 Days Following the Second Dose of H1N1 Vaccine

Number of Participants Age 65 Years and Older With 4-fold or Greater Hemagglutination Inhibition Assay (HAI) Antibody Titer Increases Against the Influenza H1N1 2009 Virus 21 Days Following the Second Dose of H1N1 Vaccine

Number of Participants Age 18 to 64 Years With a Serum Hemagglutination Inhibition Assay (HAI) Antibody Titer of 1:40 or Greater Against the Virus Strains in the 2009-2010 Trivalent Influenza Vaccine (TIV) 21 Days Following the Last Vaccination

Number of Participants Age 65 Years and Older With a Serum Hemagglutination Inhibition Assay (HAI) Antibody Titer of 1:40 or Greater Against the Virus Strains in the 2009-2010 Trivalent Influenza Vaccine (TIV) 21 Days Following the Last Vaccination

Number of Participants Age 18 to 64 Years With a Serum Hemagglutination Inhibition Assay (HAI) Antibody Titer of 1:40 or Greater Against the H1N1 2009 Virus 21 Days Following the Second Dose of H1N1 Vaccine

Number of Participants Age 65 Years and Older With a Serum Hemagglutination Inhibition Assay (HAI) Antibody Titer of 1:40 or Greater Against the H1N1 2009 Virus 21 Days Following the Second Dose of H1N1 Vaccine

Detailed description: 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

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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 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.

Emory Vaccine Center - The Hope Clinic, Decatur, Georgia 30030, United States

Saint Louis University Hospital - Internal Medicine - Infectious Diseases, Allergy & Immunology, St. Louis, Missouri 63110, United States

Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, United States

Vanderbilt University - Pediatric - Vanderbilt Vaccine Research Center, Nashville, Tennessee 37232-2573, United States

Baylor College of Medicine, Houston, Texas 77030, United States

Starting date: August 2009
Last updated: July 26, 2012