Safety of RIV4 Versus IIV4 in Pregnant Women

NCT03969641 | Completed Phase 4 Results FDA Drug

• 1 other identifier: Pro00101707
• Study Type: interventional
• Target: 384
• Locations: 1 country
• Sites: 3

Brief Summary

This is a prospective, randomized clinical trial. During the study, pregnant women will be randomized (1:1) to receive RIV4 or IIV4. Vaccines will be administered by licensed providers. Prior influenza vaccine history will be verified by medical record review when possible. Injection-site (local) and systemic reaction data will be assessed on vaccination day and during the 8 days following vaccination using either identical web-based or paper diaries, depending on study participant preference. Maternal serum samples will be collected for antibody titers relevant to Influenza at time points that include: prior to vaccination and \~29 days post vaccination. When feasible, maternal blood at delivery and cord blood serum will be analyzed for the same antibody titers. Pregnant women will be followed through delivery with comprehensive obstetric and neonatal outcomes obtained from medical record review for 90 days of life.

Conditions

Safety; Adverse Event Following Immunisation; Birth Outcomes

Keywords

Vaccination; Safety; Birth outcomes; Flublok; Pregnant; Influenza

Outcome Measures

Primary Outcomes (1)

• Number of Pregnant Women Vaccinated With RIV4 Versus IIV4 With Adverse Birth Outcomes

  As measured by the number of women experiencing one of the following: * Adverse birth outcome is a composite of occurrence of at least one of the following: preterm birth, spontaneous abortion, fetal death, or neonatal death. * Preterm birth- born alive at less than 37 weeks and 0 days gestation * Spontaneous abortion (SAB)- pregnancy loss prior to 20 weeks 0 days * Fetal death- intrauterine death of fetus at or after 20 weeks 0 days * Neonatal death- infant death within first 28 days of life

  Birth outcomes were monitored within postnatal day 28.

Secondary Outcomes (4)

• Number of Pregnant Women With Preterm Birth After RIV4 Versus IIV4 Vaccination

  Birth outcomes were monitored through 36 weeks 6 days gestation.

• Number of Pregnant Women With Fetal or Neonatal Death After RIV4 Versus IIV4 Vaccination

  Birth outcomes were monitored through postnatal day 28.

• Number of Pregnant Women With Spontaneous Abortion After RIV4 Versus IIV4 Vaccination

  Birth outcomes were monitored through 19 weeks 6 days gestation.

• Number of Pregnant Women With Moderate/Severe Solicited Reactogenicity Events (Local and Systemic) Within 8 Days After Vaccination With RIV4 Versus IIV4

  Reactogenicity was measured for 8 days post-vaccination.

Study Arms (2)

RIV4

EXPERIMENTAL

The first recombinant inactivated influenza vaccine (RIV) using an insect baculovirus expression system and recombinant DNA technology

Biological: Quadrivalent Recombinant Influenza Vaccine

IIV4

ACTIVE COMPARATOR

Standard inactivated influenza vaccine (IIV) manufactured involving the use of embryonated hen eggs.

Biological: Quadrivalent Inactivated Influenza Vaccine

Interventions

Quadrivalent Recombinant Influenza Vaccine BIOLOGICAL

The first recombinant inactivated influenza vaccine (RIV) using an insect baculovirus expression system and recombinant DNA technology

Also known as: Flublok Quadrivalent

RIV4

Quadrivalent Inactivated Influenza Vaccine BIOLOGICAL

Standard inactivated influenza vaccine (IIV) manufactured involving the use of embryonated hen eggs.

Also known as: Flulaval

IIV4

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Pregnant, as determined by medical history
• Age ≥ 18 years of age at enrollment
• Intention of receiving influenza vaccine based on ACIP-CDC guidelines
• Willing to provide written informed consent prior to initiation of any study procedures
• Gestational age at vaccination ≤ 34 weeks 0 days based on reconciliation of last menstrual period and ultrasound dating. Estimated due date (EDD) and Gestational Age (GA-EDD) will be based on reconciliation of "sure" first day of the last menstrual period (LMP) and earliest dating ultrasound. If the LMP is uncertain, then the earliest dating ultrasound will be used to determine EDD and GA. If the ultrasound derived-EDD is in agreement with sure-LMP derived EDD, then the LMP-derived EDD is used to determine GA. If the ultrasound derived EDD is not in agreement with the LMP-derived EDD, the ultrasound-derived EDD is used to determine GA.
• English or Spanish literate
• Intention of being available for entire study period and complete all relevant study procedures, including follow-up phone calls and collection of delivery information.

You may not qualify if:

• Influenza vaccine receipt during 2019-2020 or 2020-2021 influenza season prior to study enrollment.
• Participation in this study in 2019-2020 influenza season
• Any condition that may interfere with assessment of local injection site reactions, e.g. obscuring tattoos
• Known or suspected immunosuppression as a result of an underlying illness or treatment
• Use of anti-cancer chemotherapy or radiation therapy within the preceding 36 months
• Use of oral or parenteral corticosteroids (≥ 20mg/day prednisone equivalent) or high-dose inhaled glucocorticoid for ≥ 14 consecutive days within the preceding 30 days
• 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 is acceptable)
• Has a history of receiving immunoglobulin or other blood product (with exception of Rh immunoglobulin) within the 3 months prior to study vaccination.
• History of febrile illness (\> 100.4°F or 38°C) within the past 24 hours prior to study vaccination
• Contraindication to IIV or RIV receipt including history of severe allergic reaction after a previous dose of any influenza vaccine; or to a vaccine component, including egg protein
• History of Guillain-Barré syndrome within 6 weeks of a prior dose of any influenza vaccine
• Receipt of any licensed vaccine within 7 days prior to study vaccination or intention of receiving any vaccines during 8-day post-vaccination period
• Receipt of live vaccine during current pregnancy
• Signs or symptoms of active preterm labor, defined as regular uterine contractions with cervical change (dilation/effacement)
• Known multi-fetal gestation or fetal congenital anomaly, e.g. genetic abnormality or major congenital malformation based on antenatal ultrasound

Sponsors & Collaborators

• Duke University: lead
• Children's Hospital Medical Center, Cincinnati: collaborator
• Boston Medical Center: collaborator
• Centers for Disease Control and Prevention: collaborator

Study Sites (3)

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

Duke University Medical Center

Durham, North Carolina, 27705, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

MeSH Terms

Conditions

Influenza, Human

Interventions

Influenza Vaccines; FluLaval

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Results Point of Contact

• Title: Dr. Geeta Swamy
• Organization: Duke University

geeta.swamy@duke.edu

919.681.5220

Study Officials

• Geeta K Swamy, MD

  Duke University

  PRINCIPAL INVESTIGATOR

• Karen R Broder, MD

  Centers for Disease Control and Prevention

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 28, 2019
• First Posted: May 31, 2019
• Study Start: September 5, 2019
• Primary Completion: September 29, 2021
• Study Completion: September 29, 2021
• Last Updated: January 11, 2023
• Results First Posted: December 27, 2022

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)