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H1N1 Vaccine in Pregnant Women

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00963430
Recruitment Status : Completed
First Posted : August 21, 2009
Results First Posted : May 16, 2011
Last Update Posted : December 3, 2012
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Tracking Information
First Submitted Date  ICMJE August 20, 2009
First Posted Date  ICMJE August 21, 2009
Results First Submitted Date  ICMJE April 21, 2011
Results First Posted Date  ICMJE May 16, 2011
Last Update Posted Date December 3, 2012
Study Start Date  ICMJE September 2009
Actual Primary Completion Date May 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 21, 2011)
  • Number of Participants Reporting Solicited Subjective Local Reactions After First Vaccination [ Time Frame: Within 8 days (Day 0-7) post first vaccination ]
    Participants maintained a memory aid to record daily the occurrence of local reactions of pain, tenderness and swelling for 8 days after vaccination (Day 0-7) based on their interference with daily activities. Participants are counted if they were reported as experiencing the symptom at any severity on any of the 8 days.
  • Number of Participants Reporting Solicited Subjective Local Reactions After Second Vaccination [ Time Frame: Within 8 days (Day 0-7) post second vaccination ]
    Participants maintained a memory aid to record daily the occurrence of local reactions of pain, tenderness and swelling for 8 days after vaccination (Day 0-7) based on their interference with daily activities. Participants are counted if they were reported as experiencing the symptom at any severity on any of the 8 days.
  • Number of Participants Reporting Solicited Quantitative Local Reactions After First Vaccination [ Time Frame: Within 8 days (Day 0-7) post first vaccination ]
    Participants maintained a memory aid to record daily the occurrence of local reactions of redness and swelling for 8 days after vaccination (Day 0-7). If the reaction was present, the maximum diameter was measured in millimeters (mm). Participants are counted if they reported experiencing the reaction with any measurement greater than 0 mm on any of the 8 days.
  • Number of Participants Reporting Solicited Quantitative Local Reactions After Second Vaccination [ Time Frame: Within 8 days (Day 0-7) post second vaccination ]
    Participants maintained a memory aid to record daily the occurrence of local reactions of redness and swelling for 8 days after vaccination (Day 0-7). If the reaction was present, the maximum diameter was measured in millimeters (mm). Participants are counted if they reported experiencing the reaction with any measurement greater than 0 mm on any of the 8 days.
  • Number of Participants Reporting Solicited Subjective Systemic Reactions After First Vaccination [ Time Frame: Within 8 days (Day 0-7) post 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 after vaccination (Day 0-7) 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.
  • Number of Participants Reporting Solicited Subjective Systemic Reactions After Second Vaccination [ Time Frame: Within 8 days (Day 0-7) post 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 after vaccination (Day 0-7) 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.
  • Number of Participants Reporting Fever After First Vaccination [ Time Frame: Within 8 days (Day 0-7) post first vaccination ]
    Participants were provided with a thermometer and a memory aid on which to record daily oral temperatures for 8 days after vaccination (Day 0-7). The protocol defined fever as oral temperature of 37.8 degrees Celsius or higher. Participants are counted as experiencing fever if they reported oral temperatures of 37.8 degrees Celsius or higher on any of the 8 days.
  • Number of Participants Reporting Fever After Second Vaccination [ Time Frame: Within 8 days (Day 0-7) post second vaccination ]
    Participants were provided with a thermometer and a memory aid on which to record daily oral temperatures for 8 days after vaccination (Day 0-7). The protocol defined fever as oral temperature of 37.8 degrees Celsius or higher. Participants are counted as experiencing fever if they reported oral temperatures of 37.8 degrees Celsius or higher on any of the 8 days.
  • Number of Participants With 4-fold or Greater Serum Hemagglutination Inhibition (HAI) Antibody Titer Increases Against Influenza H1N1 2009 Virus Following a Single Dose of H1N1 Vaccine [ Time Frame: Day 0 prior to and Day 21 after the first vaccination ]
    Blood was collected from all participants prior to the initial vaccination as well as 21 days after the first vaccination 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 vaccination titer was 1:40 or greater, or the Day 0 titer was greater than or equal to 1:10 and the Day 21 post vaccination titer was an increase by 4-fold or more.
  • Number of Participants With a Serum Hemagglutination Inhibition (HAI) Antibody Titer of 1:40 or Greater Against Influenza H1N1 2009 Virus Following a Single Dose of H1N1 Vaccine [ Time Frame: Day 21 after the first vaccination ]
    Blood was collected from all participants at Day 21 post first 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.
  • Number of Participants Reporting Maternal Complications of Pregnancy, Labor and Delivery [ Time Frame: At time of delivery ]
    Participants were contacted after delivery, and medical records reviewed, to collect complications experienced during pregnancy, labor and delivery. The data collection process followed a prospectively-defined list of complications reported for this outcome measure, some of which may have also been reported as serious adverse events if otherwise meeting those requirements.
  • Number of Participants Reporting Neonatal Complications [ Time Frame: At time of delivery ]
    Participants were contacted after delivery, and medical records reviewed, to collect neonatal complications. The data collection process followed a prospectively-defined list of complications reported for this outcome measure, some of which may have also been reported as serious adverse events if otherwise meeting those requirements.
  • Number of Participants Reporting Vaccine-associated Serious Adverse Events (SAEs) [ Time Frame: Day 0 through Day 180 after last vaccination ]
    Serious adverse events included any untoward medical occurrence that resulted in death of the mother, fetus or infant; was life threatening to mother, fetus or infant; was a persistent/significant disability/incapacity; required in-patient hospitalization or prolongation thereof; was a congenital anomaly/birth defect in fetus or infant; or may have jeopardized the mother, fetus or infant, or required intervention to prevent one of the outcomes, or was described as Guillain-Barré Syndrome. Association was determined by a clinician licensed to diagnose and listed on the site's FDA Form 1572.
Original Primary Outcome Measures  ICMJE
 (submitted: August 20, 2009)
  • Safety: occurrence of vaccine-associated serious adverse events (SAEs). [ Time Frame: Throughout the course of the study. ]
  • Safety: pregnancy outcome data-incidence of maternal and neonatal complications. [ Time Frame: At time of delivery. ]
  • Immunogenicity: proportion of subjects achieving a serum hemagglutination inhibition assay (HAI) antibody titer of greater than or equal to 1:40 against the novel influenza H1N1 2009 virus following a single dose of H1N1 vaccine (15 mcg or 30 mcg). [ Time Frame: Day 21. ]
  • Immunogenicity: proportion of subjects with 4-fold or greater hemagglutination inhibition assay (HAI) antibody titer increases against the novel influenza H1N1 2009 virus following a single dose of H1N1 vaccine (15 mcg or 30 mcg). [ Time Frame: Day 21. ]
  • Safety: occurrence of solicited local and systemic adverse events (AEs). [ Time Frame: Within 8 days post vaccination (Day 0-7). ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 21, 2011)
  • Number of Participants With a Serum Hemagglutination Inhibition Assay (HAI) Antibody Titer Greater Than or Equal to 40 Against the Novel Influenza H1N1 2009 Virus in the Maternal Blood at the Time of Delivery [ Time Frame: At time of delivery ]
    Blood was collected from participants at the time of delivery 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.
  • Number of Participants With a Serum Hemagglutination Inhibition Assay (HAI) Antibody Titer Greater Than or Equal to 40 Against the Novel Influenza H1N1 2009 Virus in Cord Blood [ Time Frame: At time of delivery ]
    Cord blood was collected at the time of delivery 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.
  • Number of Participants With 4-fold or Greater Serum Hemagglutination Inhibition (HAI) Antibody Titer Increases Against Influenza H1N1 2009 Virus Following 2 Doses of H1N1 Vaccine [ Time Frame: Day 0 prior to first vaccination and Day 21 after the second vaccination ]
    Blood was collected from all participants prior to the initial vaccination as well as 21 days after the second vaccination 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 vaccination 2 titer was 1:40 or greater, or the Day 0 titer was greater than or equal to 1:10 and the Day 21 post vaccination 2 titer was an increase by 4-fold or more.
  • Number of Participants With a Serum Hemagglutination Inhibition (HAI) Antibody Titer of 1:40 or Greater Against Influenza H1N1 2009 Virus Following 2 Doses of H1N1 Vaccine [ Time Frame: Day 21 after the second vaccination ]
    Blood was collected from all participants at Day 21 post second 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 20, 2009)
  • Immunogenicity: proportion subjects achieving a serum hemagglutination inhibition assay (HAI) antibody titer greater than or equal to 40 against the novel influenza H1N1 2009 virus in the maternal and in the umbilical cord blood. [ Time Frame: At time of delivery. ]
  • Immunogenicity: proportion of subjects achieving a serum hemagglutination inhibition assay (HAI) antibody titer of greater than or equal to 1:40 against the novel influenza H1N1 2009 virus following 2 doses of H1N1 vaccine (15 mcg or 30 mcg). [ Time Frame: Day 42 and supplemental visit. ]
  • Immunogenicity: proportion of subjects with 4-fold or greater hemagglutination inhibition assay (HAI) antibody titer increases against the novel influenza H1N1 2009 virus following 2 doses of H1N1 vaccine (15 mcg or 30 mcg). [ Time Frame: Day 42 and supplemental visit. ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE H1N1 Vaccine in Pregnant Women
Official Title  ICMJE A Phase II Study in Pregnant Women to Assess the Safety and Immunogenicity of an Unadjuvanted Sanofi Pasteur H1N1 Inactivated Influenza Vaccine Administered at Two Dose Levels
Brief Summary The purpose of this study is to evaluate an investigational 2009 H1N1 influenza vaccine to determine vaccine safety in pregnant women and the body's immune response (body's defense against disease) to different strengths of the H1N1 influenza vaccine. In this study, 2 strengths of the H1N1 influenza vaccine will be tested (given 3 weeks apart). Participants will include approximately 120 healthy pregnant women, ages 18-39 years, in their second or third trimester of pregnancy (14-34 weeks gestation). Study procedures will include 2 doses of vaccine, blood samples, cord blood samples at delivery, and recording temperature and vaccine side effects in a memory aid for 8 days following each vaccination. Participants will be involved in study related procedures for about 7 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. In addition, 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. Pregnant women are at an increased risk for the complications of influenza. A higher dose or multiple doses of an unadjuvanted, inactivated influenza H1N1 vaccine may be necessary to confer protection to this at risk population. This protocol will explore the antibody response following vaccination of pregnant women at 2 different dose levels (15 mcg and 30 mcg). The 2 doses of inactivated influenza H1N1 vaccine will be administered 21 days apart. This study will assess the immune response following a single dose of H1N1 vaccine, 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 21 days after each dose. The primary objectives are: safety, to assess the safety of unadjuvanted, inactivated H1N1influenza vaccine in pregnant women when administered at the 15 mcg or 30 mcg dose; and immunogenicity, to assess the antibody response following a single dose of unadjuvanted, inactivated H1N1 influenza vaccine in pregnant women when administered at the 15 mcg or 30 mcg dose. The secondary objectives are to: assess the antibody response following 2 doses of unadjuvanted, inactivated H1N1 influenza vaccine in pregnant women when administered at the 15 mcg or 30 mcg dose; and assess the efficiency of placental transport of maternal influenza antigen specific antibodies to the neonate. This is a randomized, double-blinded, phase II study in 120 pregnant women, ages 18-39 years. Subjects will be randomized into 2 groups (60 pregnant women per dose group) to receive intramuscular inactivated influenza H1N1 vaccine at 15 mcg (Group 1) or 30 mcg (Group 2) on Days 0 and 21. Following immunization, safety will be measured by assessment of adverse events through 21 days following the last vaccination (Day 42), serious adverse events and new-onset chronic medical conditions through 7 months post first vaccination (Day 201). Reactogenicity to the vaccine will be assessed for 8 days following each vaccination (Day 0-7). Immunogenicity testing will include HAI and neutralizing antibody testing on serum obtained on Days 0, 21 and 42. This includes samples collected prior to each vaccination and samples collected 21 days following each vaccination. HAI antibody testing will be also be performed on serum from maternal and cord blood collected at delivery.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE Influenza
Intervention  ICMJE Biological: Inactivated H1N1 Vaccine
Two doses of inactivated influenza H1N1 vaccine delivered intramuscularly (IM) as 15 or 30 mcg dose. The 15 mcg dose will be administered as a single 0.5 mL IM injection in the deltoid muscle of the preferred arm. The 30 mcg dose will be administered as a single 1.0 mL injection in the deltoid muscle.
Study Arms  ICMJE
  • Experimental: Group 2: 30 mcg H1N1 vaccine
    60 subjects to receive 30 mcg of inactivated H1N1 vaccine on Day 0 and Day 21.
    Intervention: Biological: Inactivated H1N1 Vaccine
  • Experimental: Group 1: 15 mcg H1N1 vaccine
    60 subjects to receive 15 mcg of inactivated H1N1 vaccine on Day 0 and Day 21.
    Intervention: Biological: Inactivated H1N1 Vaccine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 20, 2009)
120
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE May 2010
Actual Primary Completion Date May 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Pregnant female between the ages of 18 and 39 years, inclusive.
  • Is from 14-34 weeks of gestation, inclusive.
  • Had at least one prenatal visit during which pregnancy was confirmed.
  • Is in good health, as determined by vital signs (heart rate 100 beats per minute; blood pressure: systolic 140 mm Hg; diastolic less than or equal to 90 mm Hg; oral temperature less than 100 degrees Fahrenheit), 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 medical condition is defined as health outcomes of the specific disease are considered to be within acceptable limits in the last 3 months.
  • Able to understand and comply with planned study procedures.
  • Provides written informed consent prior to initiation of any study procedures.
  • Agrees to sign medical release for herself and her infant(s) to allow study staff to gather pregnancy outcome data, if needed per clinical site policy.

Exclusion Criteria:

  • Has a known allergy to eggs or other components in the vaccines (these may include, but are not limited to: gelatin, formaldehyde, octoxinol and chicken protein).
  • Has a history of severe reactions following previous immunization with influenza virus vaccines.
  • Has participated in a novel influenza H1N1 2009 vaccine study in the past 2 years or has history of novel influenza H1N1 2009 infection prior to enrollment.
  • Has received any other live licensed vaccines within 4 weeks or inactivated licensed vaccines within 2 weeks prior to vaccination in this study prior to vaccination or plan receipt of such vaccines within 21 days following the last vaccination (except for seasonal inactivated influenza vaccine which may be received 2 weeks post either vaccination). Measles, mumps, and rubella vaccine and tetanus, diphtheria, and acellular pertussis vaccine are permitted post-partum.
  • Has received an experimental/investigational agent (vaccine, drug, biologic, device, blood product, or medication) within one month prior to vaccination in this study, or expects to receive another experimental/investigational agent during the study period (prior to the Day 201 follow-up call - 180 days after the second vaccination).
  • Has an acute illness and/or an oral temperature greater than or equal to 100.0 degrees Fahrenheit, within 72 hours of vaccination (This may result in a temporary delay of vaccination).
  • Has immunosuppression as a result of an underlying illness or treatment, or use of anti-cancer chemotherapy or radiation therapy within the preceding 36 months.
  • Has an active neoplastic disease (excluding non-melanoma skin cancer), a history of any hematologic malignancy, current bleeding disorder, or taking anticoagulants.
  • Long term use of glucocorticoids, including oral or parenteral, or high-dose inhaled steroids (>800 micrograms/day of beclomethasone dipropionate or equivalent) within the preceding 6 months (nasal and topical steroids are allowed) or has received betamethasone or dexamethasone to accelerate fetal lung maturity.
  • Has a history of receiving immunoglobulin or other blood product (with exception of Rhogam) within the 3 months prior to enrollment in this study.
  • Has a diagnosis of a current and uncontrolled major psychiatric disorder.
  • Has been hospitalized for psychiatric illness, history of suicide attempt, or confinement for danger to self or others, within the past 10 years.
  • The subject is receiving any of the following psychiatric drugs: aripiprazole, clozapine, ziprasidone, haloperidol, molindone, loxapine, thioridazine, thiothixene, pimozide, fluphenazine, risperidone, mesoridazine, quetiapine, trifluoperazine, trifluopromazine, chlorprothixene, chlorpromazine, perphenazine, olanzapine, carbamazepine, divalproex sodium, lithium carbonate or lithium citrate. Subjects who are receiving an antidepressant drug (not listed above) and are stable for at least 3 months prior to enrollment without decompensating are allowed enrollment into the study.
  • Known active human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infection.
  • History of alcohol or drug abuse in the last 5 years.
  • Has a seizure disorder or is on an anti-seizure medication.
  • Has a history of Guillain-Barré Syndrome.
  • Plan to travel outside of North America in the time between the first vaccination and 42 days following the first vaccination.
  • Has 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 (this includes, but is not limited to, known cardiac disease, chronic liver disease, significant renal disease, unstable or progressive neurological disorder, transplant recipients or uncontrolled diabetes, juvenile diabetes (Type I) or advanced diabetes with renal disease or eye disease, diabetes controlled by diet or insulin is acceptable.)
  • Has any condition that would, in the opinion of the site investigator, place the subject at an unacceptable risk of injury or render the subject unable to meet the requirements of the protocol.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years to 39 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00963430
Other Study ID Numbers  ICMJE 09-0056
N01AI80004C
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party National Institute of Allergy and Infectious Diseases (NIAID)
Original Responsible Party Robert Johnson, HHS/NIAID/DMID
Current Study Sponsor  ICMJE National Institute of Allergy and Infectious Diseases (NIAID)
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account National Institute of Allergy and Infectious Diseases (NIAID)
Verification Date April 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP