2010-2011 Trivalent Influenza Vaccine (TIV) in Pregnant Women

NCT01173211 | Completed Phase 2 Results

• 2 other identifiers: 09-0005HHSN272200800002C
• Study Type: interventional
• Target: 183
• Locations: 1 country
• Sites: 5

Brief Summary

The purpose of this study is to see how much antibody (proteins produced by the immune system that help fight infections) the body makes after getting a flu vaccine. Researchers will also look at how the body reacts to the flu vaccine and how it affects the babies of pregnant women. The study will enroll approximately 240 women ages 18-39 years, including 180 pregnant women in their second or third trimester of pregnancy (at least 14 weeks pregnant) and 60 non-pregnant women. Participants will be randomly (by chance) assigned to 1 of 3 vaccine groups. Each participant will receive one shot of a 2010-2011 flu season licensed vaccine. The vaccine will be given as an intramuscular injection (shot in the muscle) in the upper arm. Study procedures include pregnancy testing, blood draws, and memory aids. Patient participation may be up to 8 months. The information from this study will help guide researchers in developing flu vaccines for pregnant women.

Conditions

Influenza

Keywords

pregnant, women, influenza, vaccine

Outcome Measures

Primary Outcomes (11)

• Number of Participants Reporting Vaccine-associated Unsolicited Non-serious Adverse Events

  Unsolicited non-serious adverse events were collected from participants at follow up contacts, either by phone or in clinic, through 28 days after vaccination. Association to vaccination was determined by a clinician licensed to make a medical diagnosis and listed on the site's Federal Drug Administration's Form 1572.

  Day 0 through Day 28 post vaccination

• 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.

  During the pregnancy and at the time of delivery

• Number of Participants Reporting 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 reported experiencing the symptom at any severity on any of the 8 days.

  8 days after vaccination (Days 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.

  8 days after vaccination (Days 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.

  8 days after vaccination (Days 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.

  8 days after vaccination (Days 0-7).

• Hemagglutination Inhibition Assay (HAI) Geometric Mean Titer (GMT) Against Each Antigen in the 2010-2011 Seasonal Influenza Trivalent Influenza Vaccine

  Blood was collected for HAI assay at Day 0 prior to vaccination and again at 28 days following vaccination. The HAI assay was conducted with the three antigens in the 2010-2011 seasonal inactivated TIV: Influenza B antigen, H1N1 antigen, and H3N2 antigen.

  Day 0 prior to and Day 28 following vaccination

• Number of Participants With 4-fold or Greater Serum HAI Antibody Titer Increases Against Each Antigen in the 2010-2011 Seasonal Influenza Trivalent Influenza Vaccine

  Blood was collected from all participants prior to vaccination as well as 28 days after vaccination. The HAI assay was conducted with the three antigens in the 2010-2011 seasonal inactivated TIV: Influenza B antigen, H1N1 antigen, and H3N2 antigen. A participant met the threshold of a 4-fold rise in titer if the Day 0 titer was less than 10 (the assay's lowest level of detection) and the Day 28 post vaccination titer was 40 or greater, or the Day 0 titer was greater than or equal to 10 and the Day 28 post vaccination titer was an increase by 4-fold or more.

  Day 0 prior to and Day 28 after vaccination

• Number of Participants With HAI Antibody Titer of 40 or Greater Against Each Antigen in the 2010-2011 Seasonal Influenza Trivalent Influenza Vaccine

  Blood was collected from all participants prior to vaccination as well as 28 days after vaccination. The HAI assay was conducted with the three antigens in the 2010-2011 seasonal inactivated TIV: Influenza B antigen, H1N1 antigen, and H3N2 antigen. Participants are counted if the titer at the timepoint is 40 or greater.

  Day 0 prior to and Day 28 after vaccination

Secondary Outcomes (8)

• Hemagglutination Inhibition Assay (HAI) Geometric Mean Titer (GMT) Against Each Antigen in the 2010-2011 Seasonal Influenza Trivalent Influenza Vaccine at 6 Months After Vaccination

  Day 180 (approximately 6 months after vaccination)

• Number of Participants With 4-fold or Greater Serum HAI Antibody Titer Increases Against Each Antigen in the 2010-2011 Seasonal Influenza Trivalent Influenza Vaccine at 6 Months After Vaccination

  Day 180 (approximately 6 months after vaccination)

• Number of Participants With HAI Antibody Titer of 40 or Greater Against Each Antigen in the 2010-2011 Seasonal Influenza Trivalent Influenza Vaccine at 6 Months After Vaccination

  Day 180 (approximately 6 months after vaccination)

• Maternal HAI GMT Against Each Antigen in the 2010-2011 Seasonal Influenza Trivalent Influenza Vaccine at Time of Delivery

  At time of delivery

• Number of Participants With 4-fold or Greater Maternal Serum HAI Antibody Titer Increases Against Each Antigen in the 2010-2011 Seasonal Influenza Trivalent Influenza Vaccine at Time of Delivery

  Day 0 prior to vaccination and at time of delivery

Study Arms (3)

Arm 1: Fluarix®

EXPERIMENTAL

60 pregnant women and 20 non-pregnant women to receive a single intramuscular 0.5 mL dose of Fluarix®.

Biological: Trivalent inactivated influenza vaccine

Arm 3: Fluzone®

EXPERIMENTAL

60 pregnant women and 20 non-pregnant women to receive a single intramuscular 0.5 mL dose of Fluzone®.

Biological: Trivalent inactivated influenza vaccine

Arm 2: Agriflu®

EXPERIMENTAL

60 pregnant women and 20 non-pregnant women to receive a single intramuscular 0.5 mL dose of Agriflu®.

Biological: Trivalent inactivated influenza vaccine

Interventions

Trivalent inactivated influenza vaccine BIOLOGICAL

Three licensed 2010-2011 seasonal inactivated trivalent influenza vaccines. Single intramuscular 0.5 mL dose. Each vaccine is formulated to contain 45 micrograms (mcg) hemagglutinin (HA) per 0.5 mL dose. Thimerosal is a preservative used in some vaccines. Fluzone, Agriflu and Fluarix do not contain thimerosal. For Fluarix, the tip cap and rubber plunger of the needleless prefilled syringes contain dry natural latex rubber.

Arm 2: Agriflu®

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 a singleton pregnancy and 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 \[heart rate \<100 beats per minute (bpm); blood pressure: systolic \<140 mm Hg; diastolic less than or equal to 90 mm Hg; oral temperature \<100 degrees Fahrenheit\], 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 a specific disease are considered to be within acceptable limits in the last 3 months.
• Intends to be available through 6 months following receipt of 2010-2011 seasonal influenza vaccine or until all delivery record information has been obtained, whichever is longer.
• 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 to allow study staff to gather pertinent medical information and 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 2010-2011 inactivated trivalent influenza vaccine (TIV) in the study must fulfill one of the following: (i) she is not able to bear children because she has been surgically sterilized (hysterectomy) or is at least 1 year status post tubal ligation or 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), or monogamy with vasectomized partner.
• For a female subject of childbearing potential, must have a negative pregnancy test (urine or serum) within 24 hours prior to vaccination.
• Intends to be available through 6 months following receipt of 2010-2011 inactivated TIV.
• Able to understand and comply with planned study procedures.

You may not qualify if:

• Pregnant women:
• Has received the 2010-2011 trivalent influenza vaccine (inactivated or live).
• Has a known allergy or hypersensitivity to eggs, egg proteins, latex or other components in the vaccines (including, but not limited to: formaldehyde, polyethylene glycol p-isooctylphenyl ether, sucrose, gelatin, polysorbate 80, kanamycin, polymyxin and neomycin).
• Has a history of severe reactions following previous immunization with influenza virus vaccines.
• 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 28 days following vaccination. Measles, mumps, and rubella vaccine and tetanus, diphtheria, and acellular pertussis vaccine and human papillomavirus vaccine are permitted post-partum.
• Is enrolled or plans to enroll in another interventional clinical trial with an investigational product during the current pregnancy and while participating in this study (observational studies are allowed).
• Has an acute illness and/or an oral temperature \>/= 100.0 degrees 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 (a daily aspirin may be acceptable).
• Long term use of glucocorticoids, including oral or 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) 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 infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C.

Sponsors & Collaborators

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

Study Sites (5)

Saint Louis University - Center for Vaccine Development

St Louis, Missouri, 63104-1015, United States

Location

Duke University Medical Center - Duke Perinatal Clinic

Durham, North Carolina, 27705, United States

Location

Vanderbilt University - Pediatric - Vanderbilt Vaccine Research Center

Nashville, Tennessee, 37232-2573, United States

Location

Baylor College of Medicine - Molecular Virology and Microbiology

Houston, Texas, 77030-3411, United States

Location

Group Health Research Institute - Seattle

Seattle, Washington, 98101-1466, 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: Shital M. Patel, M.D.
• Organization: Baylor College of Medicine

shitalp@bcm.edu

713-798-3793

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 29, 2010
• First Posted: July 30, 2010
• Study Start: September 1, 2010
• Primary Completion: November 1, 2011
• Study Completion: November 1, 2011
• Last Updated: December 24, 2014
• Results First Posted: January 31, 2013

Record last verified: 2013-03

Locations

US (5)