Sanofi H1N1 Influenza Vaccine Administered at Different Dose Levels With and Without AS03 Adjuvant in Healthy Adult and Elderly Populations

NCT ID: NCT00963157

Last Updated: 2014-12-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 789 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-09-30
• Study Completion Date: 2010-12-31

Brief Summary

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.

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. 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.

Conditions

Influenza

Keywords

H1N1, influenza A viruses, vaccine, elderly

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

Group 1: 3.75 mcg H1N1 vaccine + AS03 adjuvant

150 subjects (100 aged 18-64 and 50 aged greater than or equal to 65) to receive 3.75 mcg H1N1 vaccine plus AS03 adjuvant on Day 0 and Day 21.

Group Type: EXPERIMENTAL

AS03

Intervention Type: DRUG

AS03 adjuvant administered with 3.75, 7.5, or 15 mcg inactivated H1N1 vaccine.

Influenza Virus Vaccine, Monovalent A/H1N1 A/California/7/2009 NYMC X-179A

Intervention Type: BIOLOGICAL

Inactivated influenza H1N1 vaccine with AS03 adjuvant, delivered intramuscularly (IM) as 3.75, 7.5, or 15 micrograms per dose; and inactivated influenza H1N1 vaccine without adjuvant, delivered intramuscularly as 7.5 or 15 micrograms per dose. All doses of the vaccine with or without adjuvant will be administered as a single 0.5 mL IM injection in the deltoid muscle of the preferred arm.

Group 5: 15 mcg H1N1 vaccine unadjuvanted

150 subjects (100 aged 18-64 and 50 aged greater than or equal to 65) to receive 15 mcg H1N1 vaccine unadjuvanted on Day 0 and Day 21.

Group Type: EXPERIMENTAL

Influenza Virus Vaccine, Monovalent A/H1N1 A/California/7/2009 NYMC X-179A

Intervention Type: BIOLOGICAL

Inactivated influenza H1N1 vaccine with AS03 adjuvant, delivered intramuscularly (IM) as 3.75, 7.5, or 15 micrograms per dose; and inactivated influenza H1N1 vaccine without adjuvant, delivered intramuscularly as 7.5 or 15 micrograms per dose. All doses of the vaccine with or without adjuvant will be administered as a single 0.5 mL IM injection in the deltoid muscle of the preferred arm.

Group 4: 7.5 mcg H1N1 vaccine unadjuvanted

150 subjects (100 aged 18-64 and 50 aged greater than or equal to 65) to receive 7.5 mcg H1N1 vaccine unadjuvanted on Day 0 and Day 21.

Group Type: EXPERIMENTAL

Influenza Virus Vaccine, Monovalent A/H1N1 A/California/7/2009 NYMC X-179A

Intervention Type: BIOLOGICAL

Inactivated influenza H1N1 vaccine with AS03 adjuvant, delivered intramuscularly (IM) as 3.75, 7.5, or 15 micrograms per dose; and inactivated influenza H1N1 vaccine without adjuvant, delivered intramuscularly as 7.5 or 15 micrograms per dose. All doses of the vaccine with or without adjuvant will be administered as a single 0.5 mL IM injection in the deltoid muscle of the preferred arm.

Group 2: 7.5 mcg H1N1 vaccine + AS03 adjuvant

150 subjects (100 aged 18-64 and 50 aged greater than or equal to 65) to receive 7.5 mcg H1N1 vaccine plus AS03 adjuvant on Day 0 and Day 21.

Group Type: EXPERIMENTAL

AS03

Intervention Type: DRUG

AS03 adjuvant administered with 3.75, 7.5, or 15 mcg inactivated H1N1 vaccine.

Influenza Virus Vaccine, Monovalent A/H1N1 A/California/7/2009 NYMC X-179A

Intervention Type: BIOLOGICAL

Inactivated influenza H1N1 vaccine with AS03 adjuvant, delivered intramuscularly (IM) as 3.75, 7.5, or 15 micrograms per dose; and inactivated influenza H1N1 vaccine without adjuvant, delivered intramuscularly as 7.5 or 15 micrograms per dose. All doses of the vaccine with or without adjuvant will be administered as a single 0.5 mL IM injection in the deltoid muscle of the preferred arm.

Group 3: 15 mcg H1N1 vaccine + AS03 adjuvant

150 subjects (100 aged 18-64 and 50 aged greater than or equal to 65) to receive 15 mcg H1N1 vaccine plus AS03 adjuvant on Day 0 and Day 21.

Group Type: EXPERIMENTAL

AS03

Intervention Type: DRUG

AS03 adjuvant administered with 3.75, 7.5, or 15 mcg inactivated H1N1 vaccine.

Influenza Virus Vaccine, Monovalent A/H1N1 A/California/7/2009 NYMC X-179A

Intervention Type: BIOLOGICAL

Inactivated influenza H1N1 vaccine with AS03 adjuvant, delivered intramuscularly (IM) as 3.75, 7.5, or 15 micrograms per dose; and inactivated influenza H1N1 vaccine without adjuvant, delivered intramuscularly as 7.5 or 15 micrograms per dose. All doses of the vaccine with or without adjuvant will be administered as a single 0.5 mL IM injection in the deltoid muscle of the preferred arm.

Interventions

AS03

AS03 adjuvant administered with 3.75, 7.5, or 15 mcg inactivated H1N1 vaccine.

Intervention Type: DRUG

Influenza Virus Vaccine, Monovalent A/H1N1 A/California/7/2009 NYMC X-179A

Inactivated influenza H1N1 vaccine with AS03 adjuvant, delivered intramuscularly (IM) as 3.75, 7.5, or 15 micrograms per dose; and inactivated influenza H1N1 vaccine without adjuvant, delivered intramuscularly as 7.5 or 15 micrograms per dose. All doses of the vaccine with or without adjuvant will be administered as a single 0.5 mL IM injection in the deltoid muscle of the preferred arm.

Intervention Type: BIOLOGICAL

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Stanford University - Stanford Hospital and Clinics - Pediatrics - Infectious Diseases

Stanford, California, United States

Emory Vaccine Center - The Hope Clinic

Decatur, Georgia, United States

University of Iowa - Vaccine Research & Education Unit

Iowa City, Iowa, United States

University of Maryland School of Medicine - Center for Vaccine Development - Baltimore

Baltimore, Maryland, United States

Cincinnati Children's Hospital Medical Center - Infectious Diseases

Cincinnati, Ohio, United States

Group Health Research Institute - Seattle

Seattle, Washington, United States

The University of Washington - Virology Research Clinic

Seattle, Washington, United States

Countries

United States

References

Jackson LA, Chen WH, Stapleton JT, Dekker CL, Wald A, Brady RC, Edupuganti S, Winokur P, Mulligan MJ, Keyserling HL, Kotloff KL, Rouphael N, Noah DL, Hill H, Wolff MC. Immunogenicity and safety of varying dosages of a monovalent 2009 H1N1 influenza vaccine given with and without AS03 adjuvant system in healthy adults and older persons. J Infect Dis. 2012 Sep 15;206(6):811-20. doi: 10.1093/infdis/jis427. Epub 2012 Jul 10.

Reference Type: RESULT

PMID: 22782949 (View on PubMed)

Other Identifiers

09-0058

Identifier Type: -

Identifier Source: org_study_id