Novartis H1N1 Vaccine in Pregnant Women

• 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 Births With 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 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.
• Number of Participants Reporting Solicited Subjective Local Reactions After Vaccination [ Time Frame: Within 8 days post vaccination (Day 0-7) ]
  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 Vaccination [ Time Frame: Within 8 days post vaccination (Day 0-7) ]
  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 Vaccination [ Time Frame: Within 8 days post vaccination (Day 0-7) ]
  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 Vaccination [ Time Frame: Within 8 days (Day 0-7) post 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 vaccination as well as 21 days after 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 0 prior to and Day 21 following vaccination ]
  Blood was collected from all participants prior to and at Day 21 post 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.

• Safety: pregnancy outcome data: incidence of maternal and neonatal complications. [ Time Frame: At time of delivery. ]
• Safety: occurrence of solicited local and systemic adverse events (AEs). [ Time Frame: Within 8 days post vaccination (Day 0-7). ]
• Safety: occurrence of vaccine-associated serious adverse events (SAEs). [ Time Frame: Throughout the course of the study. ]
• Immunogenicity: proportion of pregnant subjects with 4-fold or greater HAI antibody titer increases against the influenza H1N1 2009 virus following a single dose of H1N1 vaccine (15 mcg or 30 mcg). [ Time Frame: Day 21. ]
• Immunogenicity: proportion of pregnant subjects achieving a serum hemagglutination inhibition (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. ]

• 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.

• Immunogenicity: proportion of pregnant subjects achieving a serum HAI antibody titer greater than or equal to 40 against the novel influenza H1N1 2009 virus in the maternal and in the cord blood. [ Time Frame: At time of delivery. ]
• Immunogenicity: proportion of pregnant subjects with 4-fold or greater HAI antibody titer increases against the influenza H1N1 2009 virus following 2 doses of H1N1 vaccine (15 mcg or 30 mcg). [ Time Frame: Day 42. ]
• Immunogenicity: proportion of pregnant subjects achieving a serum HAI antibody titer of greater than or equal to 1:40 against the influenza H1N1 2009 virus following 2 doses of H1N1 vaccine (15 mcg or 30 mcg). [ Time Frame: Day 42. ]

• Active Comparator: Group 3: Non-pregnant Women: 15 mcg H1N1 Vaccine
  100 non-pregnant women to receive 15 mcg inactivated H1N1 vaccine.
  Intervention: Biological: Inactivated H1N1 Vaccine
• Experimental: Group 2: Pregnant Women: 30 mcg H1N1 Vaccine
  100 pregnant women to receive 30 mcg inactivated H1N1 vaccine.
  Intervention: Biological: Inactivated H1N1 Vaccine
• Experimental: Group 1: Pregnant Women: 15 mcg H1N1 Vaccine
  100 pregnant women to receive 15 mcg inactivated H1N1 vaccine.
  Intervention: Biological: Inactivated H1N1 Vaccine

Inclusion Criteria:

Pregnant women:

• Pregnant female between the ages of 18 and 39 years, inclusive.
• Is from 14 weeks/0 days through 33 weeks/6 days of gestation.
• Had at least one prenatal visit during which pregnancy was confirmed.
• Is in good health, as determined by vital signs (heart rate less than or equal to 100 beats per minute; blood pressure: systolic less than or equal to 140 mm Hg; diastolic less than or equal to 90 mm Hg; oral temperature less than or equal to 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.
• Receipt of the 2009-2010 seasonal influenza vaccine no less than two weeks prior to enrollment in this study.
• Intend to be available through 6 months following receipt of H1N1 vaccine.
• 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.

Non-pregnant women:

• Female between the ages of 18-39 years, inclusive.
• For the 30 days prior to enrollment through 30 days following receipt of H1N1 vaccine must fulfill one of the following: (i) she is not able to bear children because she has been surgically sterilized (tubal ligation or hysterectomy) for at least one year or is at least 1 year post-menopausal or (ii) she agrees to practice effective methods of contraception including, but not limited to, abstinence, barrier methods (such as a condom or diaphragm) used with a spermicide, birth control pills, patches or hormonal shots or hormonal implants, NuvaRing and IUDs (intrauterine devices).
• For a female subject of childbearing potential, must have a negative pregnancy test (urine or serum) within 24 hours prior to vaccination.
• Is 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 (if indicated). 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.
• Receipt of the 2009-2010 seasonal influenza vaccine no less than two weeks prior to enrollment in this study
• Intend to be available for a follow-up visit and phone call access through 6 months following receipt of H1N1 vaccine.
• Able to understand and comply with planned study procedures.
• Provides written informed consent prior to initiation of any study procedures.

Exclusion Criteria:

Pregnant women:

• Has a known allergy or hypersensitivity to eggs or other components in the vaccines (these may include, but are not limited to: polymyxin and neomycin).
• 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, has received a H1N1 2009 vaccine or has history of novel influenza H1N1 2009 infection evaluated by a healthcare professional 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 or plan receipt of such vaccines within 21 days following vaccination. Measles, mumps, and rubella vaccine and tetanus, diphtheria, and acellular pertussis vaccine and human papillomavirus vaccine are permitted post-partum.
• Has received an experimental/investigational agent (vaccine, drug, biologic, device, blood product, or medication) within 1 month prior to vaccination in this study, or expects to receive another experimental/investigational agent during the study period (prior to 180 days post vaccination).
• Has an acute illness and/or an oral temperature >/= 100.0 F, 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 infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C.
• 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 vaccination and 21 days following 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.

Non-pregnant women:

• Has a known allergy or hypersensitivity to eggs, egg proteins, other components in the vaccines (these may include, but not limited to: polymyxin and neomycin).
• 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, has received H1N1 2009 vaccine or has history of novel influenza H1N1 2009 infection evaluated by a healthcare professional 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 or plan receipt of such vaccines within 21 days following vaccination.
• Has received an experimental/investigational agent (vaccine, drug, biologic, device, blood product, or medication) within 1 month prior to vaccination in this study, or expects to receive another experimental/investigational agent during the study period (prior to 180 days post vaccination).
• Is breastfeeding or intends to become pregnant during the study period between enrollment and 30 days following receipt of the H1N1 vaccine.
• Has an acute illness and/or an oral temperature greater than or equal to 100.0 F, 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).
• Has a history of receiving immunoglobulin or other blood product 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 infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C
• 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 vaccination and 21 days following 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.