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

NCT00963157 | Completed Phase 2 Results

• 1 other identifier: 09-0058
• Study Type: interventional
• Target: 789
• Locations: 1 country
• Sites: 7

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.

Conditions

Influenza

Keywords

H1N1, influenza A viruses, vaccine, elderly

Outcome Measures

Primary Outcomes (21)

• 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 8 Days Following the First Dose of H1N1 Vaccine

  Blood was collected from participants for testing in the HAI assay with Influenza H1N1 2009 virus as the assay antigen. A participant met the threshold of a 4-fold rise in titer if the Day 0 titer was less than 1:10 (the assay's lowest level of detection) and the Day 8 post first H1N1 vaccination titer was 1:40 or greater, or the Day 0 titer was greater than or equal to 1:10 and the Day 8 titer was an increase by 4-fold or more.

  Day 0 prior to vaccination and 8 days after the first H1N1 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 First Dose of H1N1 Vaccine

  Blood was collected from participants for testing in the HAI assay with Influenza H1N1 2009 virus as the assay antigen. A participant met the threshold of a 4-fold rise in titer if the Day 0 titer was less than 1:10 (the assay's lowest level of detection) and the Day 21 post first H1N1 vaccination titer was 1:40 or greater, or the Day 0 titer was greater than or equal to 1:10 and the Day 21 titer was an increase by 4-fold or more.

  Day 0 prior to vaccination and 21 days after the first H1N1 vaccination

• 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 8 Days Following the First Dose of H1N1 Vaccine

  Blood was collected from participants for testing in the HAI assay with Influenza H1N1 2009 virus as the assay antigen. A participant met the threshold of a 4-fold rise in titer if the Day 0 titer was less than 1:10 (the assay's lowest level of detection) and the Day 8 post first H1N1 vaccination titer was 1:40 or greater, or the Day 0 titer was greater than or equal to 1:10 and the Day 8 titer was an increase by 4-fold or more.

  Day 0 prior to vaccination and 8 days after the first H1N1 vaccination

• 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

  Blood was collected from participants for testing in the HAI assay with Influenza H1N1 2009 virus as the assay antigen. A participant met the threshold of a 4-fold rise in titer if the Day 0 titer was less than 1:10 (the assay's lowest level of detection) and the Day 21 post first H1N1 vaccination titer was 1:40 or greater, or the Day 0 titer was greater than or equal to 1:10 and the Day 21 titer was an increase by 4-fold or more.

  Day 0 prior to vaccination and 21 days after the first H1N1 vaccination

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

  Serious adverse events included any untoward medical occurrence that resulted in death; was life threatening; was a persistent/significant disability/incapacity; required in-patient hospitalization or prolongation thereof; resulted in a congenital anomaly/birth defect; may have jeopardized the participant or required intervention to prevent one of these outcomes; or was described as Guillain-Barré Syndrome. Association to vaccination was determined by a study clinician licensed to make medical diagnoses.

  Day 0 through Day 365 after the last vaccination

• Number of Participants With Hematology Laboratory Adverse Events After the First Vaccination

  Blood was drawn 8-10 days after vaccination to assess laboratory parameters at a central laboratory. Adverse events (AE) were any values that were Grade 1 or greater for the following parameters: prothrombin time (AE \>12.6 seconds), partial thromboplastin time (\>40.7 seconds), platelets (\>=401,000 or \<=129,000 cells/square millimeter), white blood cells (\>10,800 or \<3800 cells/microliter), neutrophils (\>8000 or \<1800 cells/microliter), and lymphocytes(\>4100 or \<850 cells/microliter). These parameters were not evaluated prior to enrollment as an assessment of eligibility.

  8-10 days after first vaccination

• Number of Participants With Hematology Laboratory Adverse Events After the Second Vaccination

  Blood was drawn 8-10 days after vaccination to assess laboratory parameters at a central laboratory. Adverse events (AE) were any values that were Grade 1 or greater for the following parameters: prothrombin time (AE \>12.6 seconds), partial thromboplastin time (\>40.7 seconds), platelets (\>=401,000 or \<=129,000 cells/square millimeter), white blood cells (\>10,800 or \<3800 cells/microliter), neutrophils (\>8000 or \<1800 cells/microliter), and lymphocytes(\>4100 or \<850 cells/microliter). These parameters were not evaluated prior to enrollment as an assessment of eligibility.

  8-10 days after second vaccination

• Number of Participants With Chemistry Laboratory Adverse Events After the First Vaccination

  Blood was drawn 8-10 days after vaccination to assess laboratory parameters at a central laboratory. Adverse events (AE) were any values that were Grade 1 or greater for the following parameters: sodium (AE \>146 or \<135 mEq/L), potassium (\>5.3 or \<3.5 mEq/L), creatinine (\>1.4 mg/dL), Alanine transaminase (\>52.7 U/L), Albumin (\<3.2 g/dL), and total protein (\<6.0 g/dL participants age 18-64 years, \<5.8 g/dL participants age 65 years and older). These parameters were not evaluated prior to enrollment as an assessment of eligibility.

  8-10 days after first vaccination

• Number of Participants With Chemistry Laboratory Adverse Events After the Second Vaccination

  Blood was drawn 8-10 days after vaccination to assess laboratory parameters at a central laboratory. Adverse events (AE) were any values that were Grade 1 or greater for the following parameters: sodium (AE \>146 or \<135 mEq/L), potassium (\>5.3 or \<3.5 mEq/L), creatinine (\>1.4 mg/dL), Alanine transaminase (\>52.7 U/L), Albumin (\<3.2 g/dL), and total protein (\<6.0 g/dL participants age 18-64 years, \<5.8 g/dL participants age 65 years and older). These parameters were not evaluated prior to enrollment as an assessment of eligibility.

  8-10 days after second vaccination

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

  Participants maintained a memory aid to record daily the occurrence of systemic symptoms of feverishness, malaise, myalgia, headache, nausea, chills, arthralgia, and shivering for 8 days (Day 0-7) after vaccination based on their interference with daily activities. Participants are counted if they reported experiencing the symptom at any severity on any of the 8 days.

  Within 8 days (Day 0-7) post first vaccination

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

  Participants maintained a memory aid to record daily the occurrence of systemic symptoms of feverishness, malaise, myalgia, headache, nausea, chills, arthralgia, and shivering for 8 days (Day 0-7) after vaccination based on their interference with daily activities. Participants are counted if they reported experiencing the symptom at any severity on any of the 8 days.

  Within 8 days (Day 0-7) post second vaccination

• Number of Participants Reporting Fever After the First Vaccination

  Participants were provided a thermometer and a memory aid to record daily oral temperatures for 8 days (Day 0-7) after vaccination. Participants are counted as experiencing fever if they reported oral temperatures of 38 degrees Celsius or higher on any of the 8 days.

  Within 8 days (Day 0-7) post first vaccination

• Number of Participants Reporting Fever After the Second Vaccination

  Participants were provided a thermometer and a memory aid to record daily oral temperatures for 8 days (Day 0-7) after vaccination. Participants are counted as experiencing fever if they reported oral temperatures of 38 degrees Celsius or higher on any of the 8 days.

  Within 8 days (Day 0-7) post second vaccination

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

  Participants maintained a memory aid to record daily the occurrence of local symptoms of pain, tenderness and swelling for 8 days (Day 0-7) after vaccination based on their interference with daily activities. Participants are counted if they reported experiencing the symptom at any severity on any of the 8 days.

  Within 8 days (Day 0-7) post first vaccination

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

  Participants maintained a memory aid to record daily the occurrence of local symptoms of pain, tenderness and swelling for 8 days (Day 0-7) after vaccination based on their interference with daily activities. Participants are counted if they reported experiencing the symptom at any severity on any of the 8 days.

  Within 8 days (Day 0-7) post second vaccination

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

  Participants maintained a memory aid to record daily the occurrence of local reactions of redness and swelling for 8 days (Day 0-7) after vaccination. If the reaction was present, the maximum diameter was measured in millimeters (mm). Participants are counted if they were reported as experiencing the reaction with any measurement greater than 0 mm on any of the 8 days.

  Within 8 days (Day 0-7) post first vaccination

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

  Participants maintained a memory aid to record daily the occurrence of local reactions of redness and swelling for 8 days (Day 0-7) after vaccination. If the reaction was present, the maximum diameter was measured in millimeters (mm). Participants are counted if they were reported as experiencing the reaction with any measurement greater than 0 mm on any of the 8 days.

  Within 8 days (Day 0-7) post second 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 8 Days Following the First Dose of H1N1 Vaccine

  Blood was collected from all participants 8 days after vaccination for testing in the HAI assay with Influenza H1N1 2009 virus as the assay antigen. Each sample was tested at least twice according to standard operating procedures and the result of each replicate reported. A participant is counted if the geometric mean of the replicate values was 1:40 or greater.

  Day 8 after the first 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 First Dose of H1N1 Vaccine

  Blood was collected from all participants 21 days after vaccination for testing in the HAI assay with Influenza H1N1 2009 virus as the assay antigen. Each sample was tested at least twice according to standard operating procedures and the result of each replicate reported. A participant is counted if the geometric mean of the replicate values was 1:40 or greater.

  Day 21 after the first 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 H1N1 2009 Virus 8 Days Following the First Dose of H1N1 Vaccine

  Blood was collected from all participants 8 days after vaccination for testing in the HAI assay with Influenza H1N1 2009 virus as the assay antigen. Each sample was tested at least twice according to standard operating procedures and the result of each replicate reported. A participant is counted if the geometric mean of the replicate values was 1:40 or greater.

  Day 8 after the first 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 H1N1 2009 Virus 21 Days Following the First Dose of H1N1 Vaccine

  Blood was collected from all participants 21 days after vaccination for testing in the HAI assay with Influenza H1N1 2009 virus as the assay antigen. Each sample was tested at least twice according to standard operating procedures and the result of each replicate reported. A participant is counted if the geometric mean of the replicate values was 1:40 or greater.

  Day 21 after the first vaccination

Secondary Outcomes (16)

• 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 8 Days Following the Second Dose of H1N1 Vaccine

  Day 8 after the second 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

  Day 21 after the second 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 180 Days Following the Second Dose of H1N1 Vaccine

  Day 180 after the second 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 270 Days Following the Second Dose of H1N1 Vaccine

  Day 270 after the second 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 H1N1 2009 Virus 8 Days Following the Second Dose of H1N1 Vaccine

  Day 8 after the second vaccination

Study Arms (5)

Group 1: 3.75 mcg H1N1 vaccine + AS03 adjuvant

EXPERIMENTAL

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.

Drug: AS03; Biological: Influenza Virus Vaccine, Monovalent A/H1N1 A/California/7/2009 NYMC X-179A

Group 5: 15 mcg H1N1 vaccine unadjuvanted

EXPERIMENTAL

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.

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

Group 4: 7.5 mcg H1N1 vaccine unadjuvanted

EXPERIMENTAL

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.

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

Group 2: 7.5 mcg H1N1 vaccine + AS03 adjuvant

EXPERIMENTAL

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.

Drug: AS03; Biological: Influenza Virus Vaccine, Monovalent A/H1N1 A/California/7/2009 NYMC X-179A

Group 3: 15 mcg H1N1 vaccine + AS03 adjuvant

EXPERIMENTAL

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.

Drug: AS03; Biological: Influenza Virus Vaccine, Monovalent A/H1N1 A/California/7/2009 NYMC X-179A

Interventions

AS03 DRUG

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

Group 1: 3.75 mcg H1N1 vaccine + AS03 adjuvant; Group 2: 7.5 mcg H1N1 vaccine + AS03 adjuvant; Group 3: 15 mcg H1N1 vaccine + AS03 adjuvant

Influenza Virus Vaccine, Monovalent A/H1N1 A/California/7/2009 NYMC X-179A 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 1: 3.75 mcg H1N1 vaccine + AS03 adjuvant; Group 2: 7.5 mcg H1N1 vaccine + AS03 adjuvant; Group 3: 15 mcg H1N1 vaccine + AS03 adjuvant; Group 4: 7.5 mcg H1N1 vaccine unadjuvanted; Group 5: 15 mcg H1N1 vaccine unadjuvanted

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Have alanine aminotransferase (ALT) within normal range per local or site laboratory reference ranges.
• Are able to understand and comply with planned study procedures.
• Provide written informed consent prior to initiation of any study procedures.

You may not qualify if:

• Have a known allergy to eggs or other components of the vaccine (including squalene based adjuvants, 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 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.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (7)

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

Stanford, California, 94305-2200, United States

Location

Emory Vaccine Center - The Hope Clinic

Decatur, Georgia, 30030-1705, United States

Location

University of Iowa - Vaccine Research & Education Unit

Iowa City, Iowa, 52242-2600, United States

Location

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

Baltimore, Maryland, 21201-1509, United States

Location

Cincinnati Children's Hospital Medical Center - Infectious Diseases

Cincinnati, Ohio, 45229-3026, United States

Location

Group Health Research Institute - Seattle

Seattle, Washington, 98101-1466, United States

Location

The University of Washington - Virology Research Clinic

Seattle, Washington, 98104-2433, United States

Location

Related Publications (1)

• 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.

  PMID: 22782949 RESULT

MeSH Terms

Conditions

Influenza, Human

Interventions

Influenza Vaccines

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Results Point of Contact

• Title: Lisa Jackson, MD, MPH
• Organization: Group Health Research Institute

206-442-5216

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 20, 2009
• First Posted: August 21, 2009
• Study Start: September 1, 2009
• Primary Completion: December 1, 2010
• Study Completion: December 1, 2010
• Last Updated: December 24, 2014
• Results First Posted: December 14, 2011

Record last verified: 2011-01

Locations

US (7)