A Trial to Evaluate the Efficacy and Safety of RSVpreF in Infants Born to Women Vaccinated During Pregnancy.

• ClinicalTrials.gov Identifier: NCT04424316
• Recruitment Status: Active, not recruiting
• First Posted: June 9, 2020
• Last Update Posted: March 20, 2023
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: June 3, 2020
• First Posted Date: June 9, 2020
• Last Update Posted Date: March 20, 2023
• Actual Study Start Date: June 17, 2020
• Estimated Primary Completion Date: November 24, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 8, 2020)

• The percentage reduction in the incidence of medically attended LRTI (MA-LRTI) due to RSV in infants through 180 days of life [ Time Frame: Delivery to 180 days after delivery ]
  The percentage relative risk reduction in the incidence of MA-LRTI due to RSV in the RSV vaccine group, relative to the placebo group will be assessed at specified timepoints in infant participants
• The percentage reduction in the incidence of medically attended severe LRTI due to RSV in infants through 180 days of life [ Time Frame: Delivery to 180 days after delivery ]
  The percentage relative risk reduction in the incidence of severe MA-LRTI due to RSV in the RSV vaccine group, relative to the placebo group will be assessed at specified timepoints in infant participants
• The percentage of infant participants with specific birth outcomes [ Time Frame: Birth ]
  Describe specific birth outcomes for infant participants
• The percentage of infant participants with adverse events (AEs) from birth to 1 month of age [ Time Frame: Up to 1 month of age ]
  Describe AE for infant participants from birth to 1 month of age
• The percentage of infant participants with serious adverse events (SAE) and newly diagnosed chronic medical conditions (NDCMCs) from birth to 12 months of age [ Time Frame: From birth up to 12 months of age ]
  Describe SAE and NDCMCs for infant participants from birth to 12 months of age
• The percentage of infant participants with serious adverse events (SAE) and newly diagnosed chronic medical conditions (NDCMCs) from birth to 24 months of age [ Time Frame: From birth up to 24 months of age ]
  Describe SAE and NDCMCs for infant participants from birth to 24 months of age
• Percentage of maternal participants reporting local reactions and systemic events from day of vaccination (Day 1) until Day 7 [ Time Frame: From day of vaccination until 7 days after vaccination ]
  Describe local reactions and systemic events after vaccination
• Percentage of maternal participants reporting Adverse Events (AE) within 1 month after vaccination [ Time Frame: Within 1 month after vaccination ]
  Describe adverse events (AE) after vaccination
• Percentage of maternal participants reporting SAEs [ Time Frame: From enrollment up to 180 days after delivery ]
  Describe serious adverse events from enrolment up to 180 days after delivery

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 13, 2021)

• The percentage reduction in the incidence of hospitalizations due to RSV in infants through 360 days of life [ Time Frame: Delivery to 360 days after delivery ]
  The percentage relative risk reduction in the incidence of hospitalization due to RSV in the RSV vaccine group, relative to the placebo group will be assessed at specified timepoints in infant participants
• The percentage reduction in the incidence of all-cause MA-LRTI in infant participants [ Time Frame: Delivery to 360 days after delivery ]
  The percentage relative risk reduction in the incidence of all-cause MA-LRTI in the RSV vaccine group, relative to the placebo group will be assessed at specified timepoints in infant participants
• The percentage reduction in the incidence of MA-LRTI due to RSV in infants participants [ Time Frame: Delivery to 360 days after delivery ]
  The percentage relative risk reduction in the incidence of MA-LRTI due to RSV in the RSV vaccine group, relative to the placebo group will be assessed at specified timepoints in infant participants

Original Secondary Outcome Measures (submitted: June 8, 2020)

• The percentage reduction in the incidence of hospitalizations due to RSV in infants through 180 days of life [ Time Frame: Delivery to 180 days after delivery ]
  The percentage relative risk reduction in the incidence of hospitalization due to RSV in the RSV vaccine group, relative to the placebo group will be assessed at specified timepoints in infant participants
• The percentage reduction in the incidence of all-cause MA-LRTI in infant participants [ Time Frame: Delivery to 180 days after delivery ]
  The percentage relative risk reduction in the incidence of all-cause MA-LRTI in the RSV vaccine group, relative to the placebo group will be assessed at specified timepoints in infant participants

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Trial to Evaluate the Efficacy and Safety of RSVpreF in Infants Born to Women Vaccinated During Pregnancy.
• Official Title: A PHASE 3, RANDOMIZED, DOUBLE-BLINDED, PLACEBO-CONTROLLED TRIAL TO EVALUATE THE EFFICACY AND SAFETY OF A RESPIRATORY SYNCYTIAL VIRUS (RSV) PREFUSION F SUBUNIT VACCINE IN INFANTS BORN TO WOMEN VACCINATED DURING PREGNANCY
• Brief Summary: This randomized, double-blinded, placebo-controlled Phase 3 study is designed to evaluate the efficacy and safety of maternal immunization with RSVpreF against medically attended lower respiratory tract illness (MA-LRTI) in infants.
• Detailed Description: This is a Phase 3, multicenter, randomized, double-blinded, placebo-controlled study to assess the efficacy, safety, and immunogenicity of RSVpreF or placebo (1:1 randomization) in infants born to healthy women vaccinated during pregnancy, as well as the safety and immunogenicity in the pregnant women. This will be a global study which will span multiple RSV seasons.
• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

This is a double-blinded, placebo-controlled study.

Primary Purpose: Prevention

• Condition: Respiratory Tract Infection

Intervention

• Biological: RSVpreF
  RSV vaccine (RSVpreF)
• Biological: Placebo
  Placebo

Study Arms

• Experimental: RSVpreF vaccine
  RSVpreF
  Intervention: Biological: RSVpreF
• Placebo Comparator: Placebo dose
  Placebo
  Intervention: Biological: Placebo

• Publications *: Ginsburg AS, Srikantiah P. Respiratory syncytial virus: promising progress against a leading cause of pneumonia. Lancet Glob Health. 2021 Dec;9(12):e1644-e1645. doi: 10.1016/S2214-109X(21)00455-1. Epub 2021 Nov 11. No abstract available.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: March 17, 2023): 14760
• Original Estimated Enrollment (submitted: June 8, 2020): 6900
• Estimated Study Completion Date: November 24, 2023
• Estimated Primary Completion Date: November 24, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria - Maternal Participants:

• Healthy women ≤49 years of age who are between 24 0/7 and 36 0/7 weeks of gestation on the day of planned vaccination, with an uncomplicated, singleton pregnancy, who are at no known increased risk for complications.
• Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
• Receiving prenatal standard of care based on country requirements.
• Had a fetal anomaly ultrasound examination performed at ≥18 weeks of pregnancy with no significant fetal abnormalities observed.
• Determined by medical history, physical examination, and clinical judgment to be appropriate for inclusion in the study.
• Documented negative HIV antibody test, syphilis test, and hepatitis B virus (HBV) surface antigen test during this pregnancy and prior to randomization (Visit 1).
• Intention to deliver at a hospital or birthing facility where study procedures can be obtained.
• Expected to be available for the duration of the study and can be contacted by telephone during study participation.
• Participant is willing to give informed consent for her infant to participate in the study.
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent document (ICD) and in this protocol OR If the maternal participant is illiterate, a thumbprinted informed consent must be obtained, which must be signed and dated by an impartial witness who was present throughout the entire informed consent process confirming that the maternal participant has been informed of all pertinent aspects of the study.

Inclusion Criteria -Infant Participants:

• Evidence of a signed and dated ICD signed by the parent(s)/legal guardian(s) OR If the infant participant's maternal participant/parent(s)/legal guardian(s) is illiterate, a thumbprinted informed consent must have been obtained, which must have been signed and dated by an impartial witness who was present throughout the entire informed consent process confirming that the maternal participant/parent(s)/legal guardian(s) has been informed of all pertinent aspects of the study for herself (maternal participant) and her fetus/infant prior to taking part in the study.
• Parent(s)/legal guardian(s) willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

Exclusion Criteria - Maternal Participants:

• Prepregnancy body mass index (BMI) of >40 kg/m2. If prepregnancy BMI is not available, the BMI at the time of the first obstetric visit during the current pregnancy may be used.
• Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection.
• History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the investigational product or any related vaccine.
• Current pregnancy resulting from in vitro fertilization.

• Current pregnancy complications or abnormalities at the time of consent that will increase the risk associated with the participation in and completion of the study, including but not limited to the following:

  • Preeclampsia, eclampsia, or uncontrolled gestational hypertension.
  • Placental abnormality.
  • Polyhydramnios or oligohydramnios.
  • Significant bleeding or blood clotting disorder.
  • Endocrine disorders, including untreated hyperthyroidism or untreated hypothyroidism. This also includes disorders of glucose intolerance (eg, diabetes mellitus type 1 or 2) antedating pregnancy or occurring during pregnancy if uncontrolled at the time of consent.
  • Any signs of premature labor with the current pregnancy or having ongoing intervention (medical/surgical) in the current pregnancy to prevent preterm birth.

• Prior pregnancy complications or abnormalities at the time of consent, based on the investigator's judgment, that will increase the risk associated with the participation in and completion of the study, including but not limited to the following:

  • Prior preterm delivery ≤34 weeks' gestation.
  • Prior stillbirth or neonatal death.
  • Previous infant with a known genetic disorder or significant congenital anomaly.
• Major illness of the maternal participant or conditions of the fetus that, in the investigator's judgment, will substantially increase the risk associated with the maternal or infant participant's participation in, and completion of, the study or could preclude the evaluation of the maternal participant's response (includes positive serologic testing for regional endemic conditions assessed during routine maternal care, as per local standards of care and obstetric recommendations).
• Congenital or acquired immunodeficiency disorder, or rheumatologic disorder or other illness requiring chronic treatment with known immunosuppressant medications, including monoclonal antibodies, within the year prior to enrollment.
• Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study.
• Participation in other studies involving investigational drug(s) within 28 days prior to consent and/or during study participation.
• Receipt of monoclonal antibodies within the year prior to enrollment or the use of systemic corticosteroids for >14 days within 28 days prior to study enrollment. Permitted treatments include the receipt of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) monoclonal antibodies, prednisone doses of <20 mg/day for ≤14 days and, inhaled/nebulized, intra-articular, intrabursal, or topical (skin or eyes) corticosteroids.
• Current alcohol abuse or illicit drug use. Note: Marijuana use is not considered an exclusion criterion for the study when elicited in participant screening, though it may be considered illicit in some locales.
• Receipt of blood or plasma products or immunoglobulin (Ig), from 60 days before investigational product administration, or planned receipt through delivery, with 1 exception, Rho(D) immune globulin (eg, RhoGAM), which can be given at any time.
• Previous vaccination with any licensed or investigational RSV vaccine or planned. Note: Licensed COVID-19 vaccines or COVID-19 vaccines authorized for temporary or emergency use will not be prohibited during the course of this study.
• Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or Pfizer employees, including their family members, directly involved in the conduct of the study.
• Participants who are breastfeeding at the time of enrollment.

Exclusion Criteria -Infant Participants:

o Infant who is a direct descendant (eg, child or grandchild) of the study personnel.

Sex/Gender

• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Healthy women ≤49 years of age who are between 24 and 36 weeks of gestation on the day of planned vaccination, with an uncomplicated, singleton pregnancy, who are at no known increased risk for complications.

• Ages: 0 Years to 49 Years (Child, Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Brazil, Canada, Chile, Denmark, Finland, Gambia, Japan, Korea, Republic of, Mexico, Netherlands, New Zealand, Philippines, South Africa, Spain, Taiwan, United States

Administrative Information

• NCT Number: NCT04424316
• Other Study ID Numbers: C3671008; 2019-002943-85 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
• URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

• Current Responsible Party: Pfizer
• Original Responsible Party: Same as current
• Current Study Sponsor: Pfizer
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: March 2023