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

NCT01181323 | Completed Phase 2 Results

• 2 other identifiers: 09-0007HHSN272200800006C
• Study Type: interventional
• Target: 240
• Locations: 1 country
• Sites: 6

Brief Summary

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.

Conditions

Influenza

Keywords

influenza, vaccine, breastfeeding, post-partum women, infant, LAIV, TIV, parent protocol

Outcome Measures

Primary Outcomes (10)

• Number of Participants Reporting Serious Adverse Events (SAEs)

  Serious adverse events included any untoward medical occurrence that resulted in death; was life threatening; was a persistent/significant disability/incapacity; required inpatient hospitalization or prolongation thereof; was a congenital anomaly/birth defect; or may have jeopardized the participant, or required intervention to prevent one of the outcomes, regardless of relationship to study product or study participation.

  Day 0 to Day 180 post vaccination

• Number of Participants Reporting New Onset Chronic Medical Conditions

  New onset chronic medical condition was defined as any new ICD-10 diagnosis for a participant that was expected to continue for at least 6 months and require continued health care intervention. ICD-10 = International Statistical Classification of Diseases and Related Health Problems, 10th revision. Maternal participants were asked at each visit through 180 days after enrollment if they or their infants had any new diagnosis.

  Day 0 to Day 180 post vaccination

• Number of Infant Participants Reporting Solicited Systemic Adverse Events Within 11 Days of Maternal Vaccination

  Maternal participants maintained a memory aid to record daily the occurrence in their infants of systemic adverse events of fever (defined as rectal temperature 37.8 degrees Celsius or greater), drowsiness, irritability/fussiness, loss of appetite, nasal congestion, difficulty breathing, runny nose, and cough for 11 days (Day 0-10) after maternal vaccination based on protocol-defined grading (none, mild, moderate or severe) for each symptom. Rectal temperature was measured once daily. Participants are counted if they were reported as experiencing the symptom at any severity on any of the 11 days.

  Day 0 to Day 10 post vaccination

• Number of Participating Reporting Non-serious Unsolicited Adverse Events Related to Vaccination Within 28 Days of Maternal Vaccination

  Adverse events (AE) for this protocol used the International Conference on Harmonization (ICH) guideline E6 definition of AE, any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product regardless of its causal relationship to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of investigational product. Related was defined as a reasonable possibility that the study product caused the AE. Reasonable possibility means that there is evidence to suggest a causal relationship between the study product and the adverse event. Non-serious AEs were those that did not meet the definition of serious (see Outcome Measure 1). Maternal participants were queried at each visit through 28 days after vaccination for the occurrence of any AE for her or the infant separately from the pre-defined solicited symptoms.

  Day 0 to Day 28 post vaccination

• Breast Milk ELISA IgA and IgG Geometric Mean Titers (GMT) to Each of the Vaccine Influenza Strains

  Breast milk was collected at Day 0 prior to vaccination and again at 28 days following vaccination for testing in IgA and IgG ELISA Assays. The ELISA assay was conducted with the antigens in the 2011-2012 seasonal influenza vaccine, A/Perth/16/2009 (H3N2) and B/Brisbane/60/2008, those in the 2012-2013 seasonal influenza vaccine, A/Victoria/361/2011 and B/Wisconsin/1/2010, and the antigen in both seasons's vaccine, A/California/7/2009 (H1N1). The lower limit of detection is 5.82 units/mL for IgA and 2.56 units/mL for IgG. Titers below the limit of detection were reported as one-half the limit of detection.

  Day 0 and 28 post vaccination

• Number of Infant Participants With Medically Attended Respiratory or Gastrointestinal AEs 28-42 Days After Maternal Vaccination

  Maternal participants were contacted by telephone at Day 42 to report all medically attended respiratory or gastrointestinal adverse events occurring in the infant participants between 28 and 42 days after maternal vaccination.

  Within 28-42 days after maternal vaccination

• Number of Maternal 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.

  Day 0-7 post vaccination

• Number of Maternal Participants Reporting Solicited Subjective Systemic Symptoms After Vaccination

  Participants maintained a memory aid to record daily the occurrence of systemic symptoms of feverishness, malaise, myalgia, headache, nausea, weakness, and chills 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.

  Day 0-7 post vaccination

• Number of Maternal Participants Reporting Solicited Subjective Local Symptoms After Vaccination

  Participants maintained a memory aid to record daily the occurrence of local symptoms of nasal congestion, runny nose, cough, sore throat, nasal bleeding, pain at injection site, tenderness at injection site, and swelling at injection site 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.

  Day 0-7 post vaccination

• Number of Maternal Participants Reporting Solicited Quantitative Local Symptoms 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.

  Day 0-7 post vaccination

Secondary Outcomes (12)

• Geometric Mean Titers (GMT) in Maternal Sera of Hemagglutination Inhibition (HAI) Antibodies to Each of the Influenza Strains in the Vaccine Received

  Day 0 and 28 post vaccination

• Number of Maternal Participants With Season-specific LAIV Influenza A and B Strains Detected in Respiratory Secretions Prior to Vaccination.

  Day 0 prior to vaccination

• Number of Maternal Participants With Season-specific LAIV Influenza A and B Strains Detected in Respiratory Secretions at Day 2 Post Vaccination.

  Day 2 post vaccination

• Number of Maternal Participants With Season-specific LAIV Influenza A and B Strains Detected in Respiratory Secretions at Day 8 Post Vaccination.

  Day 8 post vaccination

• Number of Infant Participants With Season-specific LAIV Influenza A and B Strains Detected in Respiratory Secretions Prior to Vaccination.

  Day 0 prior to vaccination

Study Arms (2)

Group 1: LAIV

EXPERIMENTAL

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: Cold-adapted live attenuated influenza virus vaccine, trivalent; Other: Placebo

Group 2: TIV

EXPERIMENTAL

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.

Other: Placebo; Biological: Trivalent inactivated influenza vaccine

Interventions

Placebo OTHER

0.2 ml of Intranasal placebo study product (using sucrose phosphate placebo filled sprayers), will be administered to maternal subjects.

Group 2: TIV

Cold-adapted live attenuated influenza virus vaccine, trivalent BIOLOGICAL

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.

Group 1: LAIV

Trivalent inactivated influenza vaccine BIOLOGICAL

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.

Group 2: TIV

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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).
• 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.

Sponsors & Collaborators

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

Study Sites (6)

Washington Hospital Center - Obstetrics and Gynecology

Washington D.C., District of Columbia, 20010-3017, United States

Location

Emory Children's Center - Pediatric Infectious Diseases

Atlanta, Georgia, 30322-1014, United States

Location

Saint Louis University - Center for Vaccine Development

St Louis, Missouri, 63104-1015, United States

Location

Duke Translational Medicine Institute - Clinical Vaccine Unit

Durham, North Carolina, 27704-2120, United States

Location

Cincinnati Children's Hospital Medical Center - Infectious Diseases

Cincinnati, Ohio, 45229-3026, United States

Location

Group Health Research Institute - Seattle

Seattle, Washington, 98101-1466, United States

Location

Related Publications (1)

• Brady RC, Jackson LA, Frey SE, Shane AL, Walter EB, Swamy GK, Schlaudecker EP, Szefer E, Wolff M, McNeal MM, Bernstein DI, Steinhoff MC. Randomized trial comparing the safety and antibody responses to live attenuated versus inactivated influenza vaccine when administered to breastfeeding women. Vaccine. 2018 Jul 25;36(31):4663-4671. doi: 10.1016/j.vaccine.2018.06.036. Epub 2018 Jun 28.

  PMID: 29961606 DERIVED

MeSH Terms

Conditions

Influenza, Human; Breast Feeding

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Feeding Behavior; Behavior

Results Point of Contact

• Title: Mark Steinhoff, MD
• Organization: Cincinnati Children's Hospital Medical Center

Mark.steinhoff@cchmc.org

513-636-2791

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: August 12, 2010
• First Posted: August 13, 2010
• Study Start: September 1, 2011
• Primary Completion: May 1, 2013
• Study Completion: May 1, 2013
• Last Updated: January 28, 2015
• Results First Posted: May 16, 2014

Record last verified: 2013-04

Locations

US (6)