Real-World Effectiveness of Perinatal RSV Immunoprophylaxis

RSV Infection Clinical Trial

Official title:

Real-World Effectiveness of Perinatal RSV Immunoprophylaxis

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06172660
• Other study ID #: 2000036550
• Secondary ID: 1R01AI179874-01
• Status: Not yet recruiting
• Start date: July 1, 2024
• Est. completion date: December 30, 2028

Study information

• Verified date: April 2024
• Source: Yale University
• Contact: Carlos R Oliveira, MD
• Phone: 203-785-5474
• Email: carlos.oliveira[@]yale.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The purpose of this study is to continue evaluating how well the RSV vaccines work as they are currently being used in routine clinical practice. Some of the questions that the investigators hope to answer with this study are: 1) What is the overall effectiveness of these vaccines? 2) How long does immunity last? 3) How effective are the vaccines against new strains? 3) Does the vaccine's effectiveness vary by age?

Description:

This will be a large-scale case-control study aiming to evaluate the effectiveness of perinatal RSV immunoprophylaxis. Cases and controls will be identified using active surveillance in both inpatient and outpatient clinical sites of the Yale New Haven Health System. Investigators will enroll patients seeking health care for acute respiratory illness and confirm RSV infection using approved molecular assays. Data will be collected from multiple sources, including health records, interviews, immunization registries, and population-based surveys. Investigators will generate estimates of effectiveness for each type of immunization used, disaggregated by time from immunization, disease severity, and sociodemographic characteristics (Aim 1). Investigators will also perform genetic characterization of all RSV viruses in the study, monitor the genetic diversity of the virus over time, and quantify the relative effectiveness of immunoprophylaxis against various viral lineages (Aim 2). Finally, investigators will collect acute and convalescent blood from a subset of infants and employ a single-cell and multi-omics approach to study the dynamics of the innate and adaptive immune responses during RSV infection and explore the molecular mechanisms that contribute to immunoprophylaxis failure (Aim 3).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 3750
• Est. completion date: December 30, 2028
• Est. primary completion date: December 30, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 12 Months

Eligibility

Inclusion Criteria:

• = 12 months of age at the time of presentation for evaluation for an acute respiratory infection (ARI).
• Documentation of an ARI, which is defined as an acute onset (<10 days) illness that includes: At least two of the following symptoms: fever (measured or subjective), chills, rigors, myalgia, headache, sore throat, nausea or vomiting, diarrhea, fatigue, congestion OR any one of the following: cough, shortness of breath, difficulty breathing, olfactory disorder, taste disorder, confusion, persistent chest pain, pale, gray, hypoxia, clinical or radiographic evidence of pneumonia or respiratory distress syndrome.
• Residents of Connecticut

Exclusion Criteria:

• Illness duration of >10 days at the time of respiratory specimen collection, measured from the date of the first symptom of the current acute illness.
• Parents/guardians are not able to provide informed consent To be eligible for inclusion in the study as a healthy control, an individual must meet all

of the following criteria:

• Immunized against RSV = 12 months of age
• Residents of Connecticut
• Match an enrolled case that was a vaccine failure by date of birth (±1 month), sex, and immunoprophylactic agent received (i.e., maternal vaccine vs mAb).

Related Conditions & MeSH terms

• Respiratory Syncytial Virus Infections
• RSV Infection

Intervention

Drug:
• Nirsevimab
Immunoprophylaxis against RSV

Locations

Country	Name	City	State
United States	Yale Child Health Research Center	New Haven	Connecticut

Sponsors (2)

Lead Sponsor	Collaborator
Yale University	National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall effectiveness of RSV immunoprophylaxis	The overall effectiveness of each immunoprophylactic strategy (monoclonal antibodies and maternal immunization) will be estimated separately. Logistic regression models will be used for analysis, with the outcome being case/control status and immunization status as the main predictor, controlling for known confounders.	Up to 5 years
Secondary	Relative effectiveness of RSV immunoprophylaxis by viral groups or clades.	A case-only analysis in which investigators compare the immune status among cases infected with RSV group A versus B and assess the relative effectiveness of immunization. For this analysis, logistic regression will be used to control for the time of testing and other relevant confounders.	Up to 5 years
Secondary	Kinetics of the innate and adaptive immune responses	The proportion of innate and adaptive immune cells in infants with breakthrough infections will be compared to healthy matched controls and test-negative controls. The frequency and phenotypic differences of peripheral blood immune cells during acute and convalescent blood of RSV+ infants who were both immunized and unimmunized will also be compared.	Up to 5 years