Sanofi H1N1 + TIV - Adults and Elderly

NCT00943878 | Completed Phase 2 Results

• 2 other identifiers: 09-0039N01AI80003C
• Study Type: interventional
• Target: 805
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Influenza

Keywords

H1N1, influenza A viruses, vaccine, elderly, TIV

Outcome Measures

Primary Outcomes (21)

• 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. For Group 4, this timepoint is Study Day 42, all others it is Study Day 21. 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 first H1N1 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. For Group 4, this timepoint is Study Day 42, all others it is Study Day 21. 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 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 180 after 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 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 21 post first H1N1 vaccination is Study Day 42 for Group 4, and is Study Day 21 for all other groups.

  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 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 21 post first H1N1 vaccination is Study Day 42 for Group 4, and is Study Day 21 for all other groups.

  Day 0 prior to vaccination and 21 days after the first H1N1 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, and nausea 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, and nausea 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 Subjective Systemic Reactions After the Third Vaccination

  Participants maintained a memory aid to record daily the occurrence of systemic symptoms of feverishness, malaise, myalgia, headache, and nausea 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 third 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 Fever After the Third 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 third vaccination

• Number of Participants Reporting Solicited Subjective Local Reactions After the First H1N1 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. First H1N1 vaccination was given on Study Day 0 for Groups 1, 2 and 3, and on Study Day 21 for Group 4.

  Within 8 days (Day 0-7) post first H1N1 vaccination

• Number of Participants Reporting Solicited Subjective Local Reactions After the Second H1N1 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. Second H1N1 vaccination was given on Study Day 21 for Groups 1, 2 and 3, and on Study Day 42 for Group 4.

  Within 8 days (Day 0-7) post second H1N1 vaccination

• Number of Participants Reporting Solicited Subjective Local Reactions After the TIV 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. The TIV vaccination was given on Study Day 42 for Group 1, Study Day 0 for Groups 2 and 4, and on Study Day 21 for Group 3.

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

• Number of Participants Reporting Solicited Subjective Local Reactions After the First Placebo 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. The first placebo vaccination was given on Study Day 0 for Groups 1, 3 and 4, and on Study Day 21 for Group 2.

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

• Number of Participants Reporting Solicited Subjective Local Reactions After the Second Placebo 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. The second placebo vaccination was given on Study Day 21 for Groups 1 and 4, on Study Day 42 for Groups 2 and 3.

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

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

  Participants maintained a memory aid to record daily the occurrence of local reactions of swelling and redness 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 H1N1 vaccination

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

  Participants maintained a memory aid to record daily the occurrence of local reactions of swelling and redness 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 H1N1 vaccination

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

  Participants maintained a memory aid to record daily the occurrence of local reactions of swelling and redness 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 TIV vaccination

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

  Participants maintained a memory aid to record daily the occurrence of local reactions of swelling and redness 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 placebo vaccination

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

  Participants maintained a memory aid to record daily the occurrence of local reactions of swelling and redness 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 placebo vaccination

Secondary Outcomes (8)

• 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

  Day 63

• 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

  Day 63

• 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

  Day 0 prior to vaccination and 21 days after the second 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 Second Dose of H1N1 Vaccine

  Day 0 prior to vaccination and 21 days after the second H1N1 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 Virus Strains in the 2009-2010 Trivalent Influenza Vaccine (TIV) 21 Days Following the Last Vaccination

  Day 63

Study Arms (4)

Group 3: H1N1+placebo; H1N1+TIV; placebo

EXPERIMENTAL

200 subjects (100 ages 18-64 years and 100 aged greater than or equal to 65 years) to receive: Day 0, 15 mcg H1N1 Vaccine + placebo; Day 21, 15 mcg H1N1 Vaccine + trivalent influenza vaccine (TIV); and Day 42, placebo.

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

Group 1: H1N1+placebo; H1N1+placebo; TIV

EXPERIMENTAL

200 subjects (100 ages 18-64 years and 100 aged greater than or equal to 65 years) to receive: Day 0, 15 mcg H1N1 Vaccine + placebo; Day 21, 15 mcg H1N1 Vaccine + placebo; and Day 42, trivalent influenza vaccine (TIV).

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

Group 2: H1N1+TIV; H1N1+placebo; placebo

EXPERIMENTAL

200 subjects (100 ages 18-64 years and 100 aged greater than or equal to 65 years) to receive: Day 0, 15 mcg H1N1 Vaccine + trivalent influenza vaccine (TIV); Day 21, 15 mcg H1N1 Vaccine + placebo; and Day 42, placebo.

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

Group 4: TIV+placebo; H1N1+placebo; H1N1

EXPERIMENTAL

200 subjects (100 ages 18-64 years and 100 aged greater than or equal to 65 years) to receive: Day 0, trivalent influenza vaccine (TIV) + placebo; Day 21, 15 mcg H1N1 Vaccine + placebo; and Day 42, 15 mcg H1N1 vaccine.

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

Interventions

Trivalent inactivated influenza vaccine BIOLOGICAL

Licensed trivalent influenza vaccine (TIV) administered as a single 0.5 mL intramuscular injection in the deltoid muscle.

Group 1: H1N1+placebo; H1N1+placebo; TIV; Group 2: H1N1+TIV; H1N1+placebo; placebo; Group 3: H1N1+placebo; H1N1+TIV; placebo; Group 4: TIV+placebo; H1N1+placebo; H1N1

Inactivated H1N1 Vaccine BIOLOGICAL

Two doses of inactivated influenza H1N1 vaccine, 15 mcg per dose, administered as a single 0.5 milliliters (mL) intramuscular injection in the deltoid muscle.

Group 1: H1N1+placebo; H1N1+placebo; TIV; Group 2: H1N1+TIV; H1N1+placebo; placebo; Group 3: H1N1+placebo; H1N1+TIV; placebo; Group 4: TIV+placebo; H1N1+placebo; H1N1

Placebo DRUG

Normal saline (placebo control) administered as a single 0.5 mL intramuscular injection in the deltoid muscle.

Group 1: H1N1+placebo; H1N1+placebo; TIV; Group 2: H1N1+TIV; H1N1+placebo; placebo; Group 3: H1N1+placebo; H1N1+TIV; placebo; Group 4: TIV+placebo; H1N1+placebo; H1N1

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.
• 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 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.

Sponsors & Collaborators

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

Study Sites (5)

Emory Vaccine Center - The Hope Clinic

Decatur, Georgia, 30030, United States

Location

Saint Louis University Hospital - Internal Medicine - Infectious Diseases, Allergy & Immunology

St Louis, Missouri, 63110, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229-3039, United States

Location

Vanderbilt University - Pediatric - Vanderbilt Vaccine Research Center

Nashville, Tennessee, 37232-2573, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Influenza, Human

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Sharon E. Frey, M.D.
• Organization: Division of Infectious Diseases and Immunology, Saint Louis University Medical School

freyse@slu.edu

314-977-5500

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: July 21, 2009
• First Posted: July 22, 2009
• Study Start: August 1, 2009
• Primary Completion: April 1, 2010
• Study Completion: April 1, 2010
• Last Updated: August 1, 2012
• Results First Posted: May 10, 2011

Record last verified: 2010-04

Locations

US (5)