Post-Partum Immunization With Live Attenuated Influenza Vaccine (LAIV) or Trivalent Influenza Vaccine (TIV) in Post-Partum Breast Feeding Women

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT01181323
First received: August 12, 2010
Last updated: December 5, 2013
Last verified: April 2013
  Purpose

The purpose of this research study is to learn more about the safety of 2 licensed flu vaccines, nasal spray and flu vaccine shot, in mothers and their infants, when given to women who are breastfeeding and to compare the immune response (body's defense against foreign substances) of breastfeeding mothers, who receive intranasal flu vaccine, with breastfeeding mothers receiving the flu vaccine shot. Healthy women (240 volunteers, 28-120 days post delivery) who plan to breastfeed through 28 days post vaccination and who have not received influenza vaccine for the influenza season for which they are being enrolled, will be assigned by chance to 1 of the 2 vaccines in the following manner: flu vaccine nasal spray and a placebo (inactive substance) shot or a flu vaccine shot and a placebo nasal spray. Study procedures include: nasal swabs, blood samples, and completion of memory aids. Participants will be involved in this United States based study for about 6 months.


Condition Intervention Phase
Influenza
Biological: Flumist®
Drug: Placebo (IN)
Drug: Placebo (IM)
Biological: Fluzone®
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Randomized, Double-Blind Trial, Comparing the Safety in Mothers and Their Infants and Immunogenicity in Mothers of Live Attenuated Influenza Vaccine (LAIV) to Inactivated Trivalent Influenza Vaccine (TIV) When Administered to Breast Feeding Women

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Occurrence of serious adverse events (SAEs) or new onset chronic medical conditions in maternal and infant subjects through 180 days after vaccination. [ Time Frame: Day 0 through Day 180 for maternal and infant subjects ] [ Designated as safety issue: Yes ]
  • Occurrence of solicited systemic AEs within 11 days (Day 0-10) in the infant subject [ Time Frame: Day 0-10 in the infant subject ] [ Designated as safety issue: Yes ]
  • Occurrence of non-serious AEs related to vaccination within 28 days of vaccination for both maternal and infant subject. [ Time Frame: Day 0 to day 28 in both infant and maternal subjects ] [ Designated as safety issue: Yes ]
  • Comparison of breast milk ELISA IgA and IgG GMT to each of the vaccine influenza strains in the vaccine received in Trivalent Influenza Vaccine (TIV) versus Live Attenuated Influenza Vaccine (LAIV) vaccine recipients 28 days after receipt of vaccine. [ Time Frame: 28 days after maternal receipt of vaccine. ] [ Designated as safety issue: No ]
  • Occurrence of medically attended respiratory or gastrointestinal AEs in the infant subject within 28-42 days of vaccination. [ Time Frame: Within 28-42 days after vaccination in the infant subject ] [ Designated as safety issue: Yes ]
  • Occurrence of solicited systemic and local adverse events (AEs) within 8 days after vaccination (Day 0-7) in the maternal subject. [ Time Frame: Day 0-7 in the maternal subject ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Comparison of hemagglutination inhibition antibodies and ELISA IgA and IgG GMT to each of the vaccine influenza strains in the vaccine received in sera of maternal subjects. [ Time Frame: 28 days post-vaccination of maternal subjects. ] [ Designated as safety issue: No ]
  • Detection of the LAIV virus strains in the vaccine received in maternal and infant respiratory secretions. [ Time Frame: 2 and 8 days after maternal receipt of LAIV, in both maternal and infant subjects ] [ Designated as safety issue: No ]
  • Detection of the Live attenuated influenza vaccine (LAIV) virus strains in the vaccine received in breast milk. [ Time Frame: 2 and 8 days after maternal receipt of LAIV. ] [ Designated as safety issue: No ]

Enrollment: 240
Study Start Date: September 2011
Study Completion Date: May 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1: LAIV
0.2 ml of Live attenuated influenza vaccine (LAIV), Flumist® given intranasally (IN) and 0.5 ml of placebo given intramuscularly (IM) injection administered to 120 maternal subjects.
Biological: Flumist®
Licensed product formulated for the 2011-2012 or 2012-2013 influenza season. Standard dose LAIV (Flumist®) 0.1 ml administered to maternal subjects intranasally in each nostril for a total of 0.2 mL.
Drug: Placebo (IM)
0.5 ml of Sterile saline (0.9 percent Sodium Chloride for injection), administered IM to maternal subjects.
Experimental: Group 2: TIV
0.5 ml of Inactivated Trivalent Influenza Vaccine (TIV), Fluzone® given intramuscularly (IM) and 0.2 ml of placebo given intranasally (IN) administered to 120 maternal subjects.
Drug: Placebo (IN)
0.2 ml of Intranasal placebo study product (using sucrose phosphate placebo filled sprayers), will be administered to maternal subjects.
Biological: Fluzone®
Preservative free, licensed product formulated for the 2011-2012 or 2012-2013 influenza season. Standard dose of TIV (Fluzone®) 0.5 ml administered to maternal subjects, IM in the deltoid.

Detailed Description:

Due to limited data available on the safety and immune response to live attenuated influenza vaccine (LAIV) in breast-feeding women and the lack of information on the induction of immunoglobulin (Ig) A and IgG against influenza virus in breast milk, this study compares the safety in mothers and their infants and immunogenicity in mothers of standard dose inactivated trivalent influenza vaccine (TIV) and LAIV when administered between 28-120 days of delivery in breastfeeding women. This is a multi-site, randomized, double-blinded trial in 240 post-partum breastfeeding women, 18-49 years of age and their infants. Once enrolled, a blood sample and a breast milk sample will be collected. Nasal swabs will be obtained and targeted physical examinations (TPE) will be conducted from mother and infant, if indicated. Each subject will receive either a single intramuscular (IM) 0.5 milliliter (mL) dose of TIV and 0.2 mL of placebo administered intranasally, or 0.2 mL intranasal dose of LAIV and 0.5 mL of placebo administered IM. All subjects will maintain a memory aid recording oral temperature, and systemic and local adverse events (AEs) for 8 days after study products have been administered. Approximately day 2 and 8 all subjects will return to the clinic for collection of breast milk samples and nasal swabs (mother and infant) and the memory aid will be reviewed. Approximately Day 28 after vaccination, all subjects will return to the clinic for breast milk and a blood sampling. During the time between vaccination and the day 28 visit, if mother or infant has an influenza-like illness (ILI), a clinic visit may be required within 72 hours of illness onset. The clinic visit will be required for any illness that meets the Centers for Disease Control and Prevention's definition of an ILI for the mother. Investigator discretion will discern if an illness in the infant requires an ILI visit. Any respiratory or gastrointestinal (GI) serious adverse event (SAE) in the infant will also require a clinic visit. If the mother has an ILI, nasal swabs will be collected on her, and samples from the infant (if possible). If the infant has an ILI, nasal swabs will be collected on both the mother and infant. At approximately Day 42 after vaccination, all subjects will have a phone call for assessment of any medically attended GI or respiratory illness in the infant from Day 29-42. Approximately 6 months after vaccination all subjects will have a phone call for assessment of any SAEs in the subject or the infant since Day 42. SAE data and new onset chronic medical conditions in the mother will be collected from Day 0-180. At all study visits, subjects will be asked about acute, temporary breast diseases (mastitis, abscesses) and any changes in breastfeeding, i.e., interruption and if so, how long (in weeks). Subjects will report information on current breast milk consumption by infant. Unsolicited non-serious AE data will be captured Day 0-28. Respiratory and GI AEs will be captured for the infant from Day 28-42. SAE data will be captured from Day 0-180 for both mother and infant. Blood samples will be tested for hemagglutination inhibition (HAI), IgG, and IgA as measured by enzyme linked-immunosorbent assay (ELISA). Breast milk samples will be assayed for IgA and IgG antibodies by ELISA. Breast milk and nasal swabs will also be tested for LAIV. Parent protocol to sub-study 11-0048.

  Eligibility

Ages Eligible for Study:   18 Years to 49 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Maternal Subject

  • Women age 18-49 years of age (inclusive) within 28-120 days of delivery.
  • Is in good health, as determined by vital signs (heart rate </=100 beats per minute (bpm); blood pressure: systolic <150 mm Hg; diastolic <90 mm Hg; oral temperature <100.0 degrees Fahrenheit), medical history and a targeted physical examination if indicated based on medical history.
  • Willing and capable of providing written informed consent for herself and infant.
  • Available for entire study duration, clinic visits and phone calls.
  • Planning on breast feeding from time of vaccination through 28 days post-vaccination. Breast milk must be at least one half of the source of the infant's feeding.
  • Willing to practice adequate contraception for at least 28 days after receipt of study vaccine if not surgically sterile via post-partum tubal ligation, bilateral oophorectomy or hysterectomy. Adequate contraception may include, but is not limited to, abstinence, monogamous relationship with a vasectomized partner, barrier methods such as condoms or diaphragms with spermicides, or licensed hormonal methods that are compatible with breastfeeding an infant.
  • May be reached by any IRB-approved form of communication during study period. May include telephone, email, web based, social media, and/or text messaging, based on specific local IRB recommendations.
  • Agree to sign a medical release for herself and her infant (if needed) so that study personnel may obtain medical information about her or her infant's health.

Infant The infant(s) should be in good health as assessed by medical history, interview, rectal temperature and a targeted physical examination based on medical history.

  • Infant born greater than or equal to 36 weeks gestation.
  • Successful receipt of breast milk for at least two days prior to enrollment. Breast milk must be at least one half of the source of feeding, i.e., some supplementation is acceptable.

Exclusion Criteria:

Maternal Subject

  • History of receipt of licensed influenza vaccine for the current influenza season. (If enrolled in 2011-2012 season [October 2011 - February 2012], subject must not have received 2011-2012 influenza vaccine. If enrolled in the 2012-2013 season [July 2012 or later], subject must not have received 2012-2013 influenza vaccine).
  • History of previous participation in this study.
  • Known allergy to eggs, egg proteins or other components in the vaccines (i.e. formaldehyde, polyethylene glycol, p-isooctylphenyl ether, sucrose, gelatin, polysorbate 80, gentamicin, arginine, sodium phosphate, sodium chloride, octylphenol ethoxylate, EDTA).
  • If enrolled in the 2011-2012 season, known or suspected latex allergy. For the 2012-2013 season, known or suspected latex allergy is not a reason for exclusion.
  • History of severe reactions following immunization with contemporary influenza virus vaccines.
  • Received any other licensed vaccines within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to vaccination in this study, or expects to receive a licensed vaccine during the 28 days after vaccination in this study.
  • Received an experimental/investigational agent (vaccine, drug, biologic, device, blood product, or medication) within 28 days prior to vaccination in this study, or expects to receive an experimental/investigational agent within the study time period (180 days after vaccination in this study).
  • Received antiviral agent against influenza A and/or B within 48 hours prior to vaccination in this study. Antiviral agents should not be administered until 2 weeks after vaccination in this study unless medically necessary.
  • A moderate to severe acute illness and/or an oral temperature >/= 100.0 F, within 72 hr prior to vaccination. (This may result in a temporary delay of vaccination).
  • Immunosuppression as a result of an underlying illness or treatment, or use of anti-cancer chemotherapy or radiation therapy within the preceding 36 months.
  • Active neoplastic disease or a history of any hematologic malignancy (cancers of blood or bone marrow) or current bleeding or blood clotting disorder.
  • Current diagnosis of asthma.
  • History of asthma, wheezing, or bronchospasm in the last 5 years.
  • Long term (at least 14 days of prednisone 2 mg/kg or equivalent other glucocorticoid) use of oral or parenteral steroids, high-dose inhaled steroids (>800 microgram/day of beclomethasone dipropionate or equivalent) within the preceding 6 months (topical steroids are allowed).
  • Use of intranasal steroids within 14 days prior to vaccination in this study or within 14 days after receipt of study vaccine.
  • Use of intranasal products within 6 hours prior to vaccination in this study or expects to use intranasal products within 6 hours post study vaccination.
  • History of receiving immunoglobulin or other blood product (with exception of RhoGAM) within the 3 months prior to vaccination in this study.
  • Diagnosis of a current and uncontrolled major psychiatric disorder.
  • Has been hospitalized within the past 10 years for psychiatric illness, suicide attempt, or confinement for danger to self or others.
  • The subject is receiving listed 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 a single antidepressant drug and are stable for at least 3 months prior to enrollment without decompensating are allowed enrollment into the study.
  • The subject is receiving medications contraindicated with breast feeding.
  • Known active human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infection.
  • An active neurological (such as, but not limited to seizure disorder), auto-immune or vascular disease.
  • Active breast infection or breast abscess. (Study vaccination will be delayed until this breast infection or breast abscess has been treated and is resolved.)
  • History of frequent epistaxis (nose bleeds).
  • History of alcohol or drug abuse in the 1 year prior to enrollment.
  • History of Guillain-Barré syndrome.
  • Any known immunocompromised family member/household contact (such as active cancer, lupus, inflammatory bowel disease, HIV infection, or receipt of an organ or bone marrow transplant).
  • Has an acute or chronic medical condition that, in the opinion of the investigator would interfere with the evaluation of responses (this includes, but is not limited to: known chronic liver, lung or heart disease, chronic anemia, metabolic disorders such as diabetes (resolved gestational diabetes is acceptable), significant renal disease, transplant recipients).
  • Pregnant or planning to become pregnant during the 28 days after receipt of study vaccine.
  • 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.

Infant

  • Major congenital malformations.
  • Syndromes that affect breastfeeding.
  • Progressive neurological disease or a history of any seizure.
  • Chronic lung disease or oxygen requirement for heart disease.
  • History of bronchopulmonary dysplasia, wheezing, reactive airway disease, hospitalization for respiratory illness, or use of bronchodilators.
  • Any receipt of glucocorticoids.
  • Immunodeficiency disease or use of immunosuppressive therapy including perinatal exposure to or infection with HIV, or known infection with hepatitis B or hepatitis C.
  • Received an experimental/investigational agent (vaccine, drug, biologic, device, blood product, or medication) within 28 days prior to this study, or expects to receive an experimental/investigational agent within the study time period (180 days after mother's vaccination in this study).
  • A moderate to severe acute illness and/or a rectal temperature greater than or equal to 100.0 F (37.8 C), within 72 hours prior to mother's vaccination (This may result in a temporary delay of vaccination in mother).
  • Received any licensed vaccines within 7 days prior to mother's vaccination in this study, or expects to receive a licensed vaccine during the 10 days after mother's vaccination in this study (This may result in a temporary delay of vaccination in mother).
  • History of documented laboratory-confirmed influenza infection.
  • Receipt of blood or blood products.
  • Have a condition that may place the infant at an unacceptable risk of injury or would make it difficult for the infant to meet the requirements of the study.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01181323

Locations
United States, District of Columbia
Washington Hospital Center - Obstetrics and Gynecology
Washington, District of Columbia, United States, 20010-3017
United States, Georgia
Emory Children's Center - Pediatric Infectious Diseases
Atlanta, Georgia, United States, 30322-1014
United States, Missouri
Saint Louis University - Center for Vaccine Development
Saint Louis, Missouri, United States, 63104-1015
United States, North Carolina
Duke Translational Medicine Institute - Clinical Vaccine Unit
Durham, North Carolina, United States, 27704-2120
United States, Ohio
Cincinnati Children's Hospital Medical Center - Infectious Diseases
Cincinnati, Ohio, United States, 45229-3026
United States, Washington
Group Health Research Institute - Seattle
Seattle, Washington, United States, 98101-1466
Sponsors and Collaborators
  More Information

No publications provided

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT01181323     History of Changes
Other Study ID Numbers: 09-0007, N01AI80006C
Study First Received: August 12, 2010
Last Updated: December 5, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
influenza, vaccine, breastfeeding, post-partum women, infant, LAIV, TIV, parent protocol

Additional relevant MeSH terms:
Influenza, Human
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on April 15, 2014