Novartis H1N1 Vaccine in Pregnant Women

NCT00992719 | Completed Phase 2 Results

• 2 other identifiers: 09-0072N01AI80057C
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 6

Brief Summary

The purpose of this study is to evaluate the safety of a 2009 H1N1 influenza vaccine in pregnant women and to determine how their body reacts to different strengths of the vaccine. Two strengths of the H1N1 influenza vaccine will be tested. Since it is not known if the response to the vaccine in pregnant women is the same or different than in non-pregnant women, the study also includes a group of women who are not pregnant for comparison. Participants include 200 pregnant women and 100 non-pregnant women ages 18-39. Study procedures include physical exams, several blood samples and maintaining a memory aid to document daily temperature and side effects for 8 days following vaccination. Participants will be involved in study related procedures for about 6 months.

Conditions

Influenza

Keywords

H1N1, influenza A viruses, vaccine, pregnant women

Outcome Measures

Primary Outcomes (9)

• Number of Participants Reporting Maternal Complications of Pregnancy, Labor and 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.

  At time of delivery

• Number of Births With Neonatal Complications

  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.

  At time of delivery

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

  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.

  Day 0 through Day 180 after vaccination

• Number of Participants Reporting Solicited Subjective Local Reactions After 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.

  Within 8 days post vaccination (Day 0-7)

• Number of Participants Reporting Solicited Quantitative Local Reactions After 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.

  Within 8 days post vaccination (Day 0-7)

• Number of Participants Reporting Solicited Subjective Systemic Reactions After 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.

  Within 8 days post vaccination (Day 0-7)

• Number of Participants Reporting Fever After 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.

  Within 8 days (Day 0-7) post vaccination

• 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

  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.

  Day 0 prior to and Day 21 after the first vaccination

• 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

  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.

  Day 0 prior to and Day 21 following vaccination

Secondary Outcomes (2)

• 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

  At time of delivery

• 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

  At time of delivery

Study Arms (3)

Group 3: Non-pregnant Women: 15 mcg H1N1 Vaccine

ACTIVE COMPARATOR

100 non-pregnant women to receive 15 mcg inactivated H1N1 vaccine.

Biological: Inactivated H1N1 Vaccine

Group 2: Pregnant Women: 30 mcg H1N1 Vaccine

EXPERIMENTAL

100 pregnant women to receive 30 mcg inactivated H1N1 vaccine.

Biological: Inactivated H1N1 Vaccine

Group 1: Pregnant Women: 15 mcg H1N1 Vaccine

EXPERIMENTAL

100 pregnant women to receive 15 mcg inactivated H1N1 vaccine.

Biological: Inactivated H1N1 Vaccine

Interventions

Inactivated H1N1 Vaccine BIOLOGICAL

H1N1 vaccine \[Influenza A (H1N1) 2009 Monovalent Vaccine\] is a licensed, inactivated influenza virus vaccine. It will be provided as prefilled single dose syringes containing 0.5 mL. The 0.5 mL prefilled syringe is formulated without preservative. The 15 microgram (mcg) dose will be administered as a single 0.5 mL intramuscular (IM) injection in the deltoid muscle of the preferred arm. The 30 mcg dose will be administered as two 0.5 mL injections in the deltoid muscle of each arm.

Group 1: Pregnant Women: 15 mcg H1N1 Vaccine; Group 2: Pregnant Women: 30 mcg H1N1 Vaccine; Group 3: Non-pregnant Women: 15 mcg H1N1 Vaccine

Eligibility Criteria

• Age: 18 Years - 39 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• Receipt of the 2009-2010 seasonal influenza vaccine no less than two weeks prior to enrollment in this study

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (6)

University of Maryland Baltimore

Baltimore, Maryland, 21201, United States

Location

Saint Louis University - Center for Vaccine Development

St Louis, Missouri, 63104, United States

Location

Duke University Medical Center

Durham, North Carolina, 27705, United States

Location

Vanderbilt University

Nashville, Tennessee, 37232-2573, United States

Location

Baylor College of Medicine - Department of Molecular Virology and Microbiology

Houston, Texas, 77030, United States

Location

Group Health Cooperative

Seattle, Washington, 98101, 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

Limitations and Caveats

Although 200 pregnant and 100 non-pregnant subjects were targeted for enrollment, enrollment closed in May 2010 prior to reaching the target due to slow accrual.

Results Point of Contact

• Title: Geeta K. Swamy, M.D.
• Organization: Department of Obstetrics & Gynecology, Division of Maternal-Fetal Medicine, Duke University School of Medicine

geeta.swamy@duke.edu

919-681-5220

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 8, 2009
• First Posted: October 9, 2009
• Study Start: November 1, 2009
• Primary Completion: February 1, 2011
• Study Completion: February 1, 2011
• Last Updated: August 7, 2013
• Results First Posted: March 5, 2012

Record last verified: 2010-07

Locations

US (6)