The Immunology and Safety of Maternal RSV Vaccination (ABRYSVO), Infant Nirsevimab (BEYFORTUS) Immunization, or Both Products
NCT Number: NCT06551506
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE4
Conditions: Respiratory Syncytial Virus Infection
Interventions: BIOLOGICAL: Abrysvo|BIOLOGICAL: Beyfortus
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sex: FEMALE
Age: ADULT
Enrollment: 200
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: NONE|Primary Purpose: PREVENTION
Start Date: 2024-09-15
Completion Date: 2025-11-15
Locations: Emory University School of Medicine, Atlanta, Georgia, 30322-1013, United States|University of Maryland, School of Medicine, Center for Vaccine Development and Global Health, Baltimore, Maryland, 21201-1509, United States|New York University School of Medicine - Langone Medical Center - Vaccine Center, New York, New York, 10016-6402, United States|University of Rochester Medical Center - Vaccine Research Unit, Rochester, New York, 14611-3201, United States|Cincinnati Children's Hospital Medical Center Vaccine Research Center, Cincinnati, Ohio, 45229-3039, United States|University of Pittsburgh - Medicine - Infectious Diseases, Pittsburgh, Pennsylvania, 15213-3108, United States|Vanderbilt University Medical Center, Nashville, Tennessee, 37212, United States|Baylor College of Medicine, Houston, Texas, 77030-3411, United States

Summary:
Respiratory Syncytial Virus (RSV) is the leading cause of lower respiratory tract infections (LRTIs) in infants and young children. It is also a leading cause of mortality in children \<5 years of age worldwide. Until recently, no Food and Drug Administration (FDA)-approved vaccines were available to prevent RSV infection. The only prophylactic product for RSV prevention recommended for infants was the monoclonal antibody palivizumab, but administration was limited to those with extreme prematurity, chronic lung disease, or hemodynamically significant congenital heart disease. However, in 2023, the FDA approved two products designed to prevent RSV lower respiratory tract disease (LRTD) in all infants: an active RSV vaccine based on the prefusion F protein (RSVpreF, ABRYSVO, Pfizer) administered during pregnancy, and a passive, long-acting monoclonal antibody (nirsevimab-alip \[henceforth referred to as nirsevimab\], BEYFORTUS, AstraZeneca) administered to infants at birth or at the start of their first RSV season. Both products were evaluated in Phase 3 pivotal clinical trials and have high efficacy in preventing LRTD caused by RSV in infants. Although there is no established correlate of protection against RSV, antibodies have been associated with protection across multiple studies. The clinical development plan for the products did not include comprehensive evaluations of the magnitude and durability of the immune response, nor were the two products tested in a single trial. This study is a prospective, randomized, open-label Phase 4 study with the primary objective of evaluating the magnitude and durability of RSV-specific neutralizing antibodies in infants through 12 months of life following either maternal RSV vaccination, infant nirsevimab administration, or both products combined.

Primary Outcome Measures: Geometric mean titer (GMT) of serum RSV A and B neutralizing antibodies in infants, GMT of RSV A and B neutralizing antibodies in infant serum at Day 1, 43, 91, 181, and 366. Day 1 infant specimen represents infant cord blood or serum (if unable to collect cord blood). Mother-infant pairs will be randomized 1:1 to either Day 43 or Day 91 blood collection., Through Day 366
Secondary Outcome Measures: Frequency and relatedness of serious adverse events (SAEs) in each study arm (infants only), Number of participants that experienced SAEs by relatedness in each study arm, Through Day 181|Frequency and severity of unsolicited Grade 3 or higher related adverse events (AEs), Number of participants that experienced unsolicited Grade 3 or higher related AEs by severity, Through 30 days following each nirsevimab dose|Frequency and severity of medically attended adverse events (MAAEs), Number of participants that experienced MAAEs by severity, Through 30 days following each nirsevimab dose|Geometric mean titer (GMT) of RSV A and B neutralizing antibodies in cord blood, GMT of RSV A and B neutralizing antibodies in cord blood, Day 1|Geometric mean titer (GMT) of RSV pre-F binding IgA antibodies in breast milk, GMT of RSV pre-F binding IgA antibodies in breast milk, Through Day 366|Geometric mean titer (GMT) of RSV pre-F binding IgG antibodies in breast milk, GMT of RSV pre-F binding IgG antibodies in breast milk, Through Day 366|Geometric mean titer (GMT) of RSV pre-F binding IgG antibodies in cord blood, GMT of RSV pre-F binding IgG antibodies in cord blood, Day 1|Geometric mean titer (GMT) of serum RSV A and B neutralizing antibodies in mothers, GMT of serum RSV A and B neutralizing antibodies in mothers that had infant cord blood collected, Day 1|Geometric mean titer (GMT) of serum RSV A and B neutralizing antibodies in mothers, GMT of RSV A and B neutralizing antibodies in maternal serum. Mother-infant pairs will be randomized 1:1 to either Day 43 or Day 91 blood collection., Through Day 366|Geometric mean titer (GMT) of serum RSV pre-F binding IgG antibodies in infants n, GMT of RSV pre-F binding IgG antibodies in infant serum. Day 1 infant specimen represents infant cord blood or serum (if unable to collect cord blood). Mother-infant pairs will be randomized 1:1 to either Day 43 or Day 91 blood collection., Through Day 366|Geometric mean titer (GMT) of serum RSV pre-F binding IgG antibodies in mothers, GMT of serum RSV pre-F binding IgG antibodies in mothers that had infant cord blood collected, Day 1|Geometric mean titer (GMT) of serum RSV pre-F binding IgG antibodies in mothers, GMT of RSV pre-F binding IgG antibodies in maternal serum. Mother-infant pairs will be randomized 1:1 to either Day 43 or Day 91 blood collection., Through Day 366|Occurrence of local solicited adverse reaction, Number of participants that experienced any local solicited adverse reactions including injection site erythema/redness, injection site edema/induration, and injection site pain/tenderness, Through 7 days following each nirsevimab dose|Occurrence of systemic solicited adverse reaction, Number of participants that experienced any systemic solicited adverse reactions including fever (axillary), sleepiness/fatigue, irritability/crying, and loss of appetite, Through 7 days following each nirsevimab dose