The EMBRACE Study: Enflonsia Monoclonal in Babies - RSV Antibody Concentration Evaluation

The study will enroll 24 infants younger than 8 months who are entering their first RSV season. The study includes minors and may include newborn infants. Written permission will be obtained from a parent or legally authorized representative before any study procedures occur. Infant assent will not be obtained because the participants are too young to provide it.

Each infant will receive one injection of clesrovimab as part of the usual care recommended to prevent serious RSV illness. Study staff will collect blood and nasal samples before the injection, at either Day 8 or Day 45, and at Day 181 after injection. Parent or legally authorized representative will also complete one safety follow-up visit by phone call at either Day 8 or Day 45.

Each infant will participate for about six months after receiving clesrovimab. Recruitment will invite families of eligible infants through the Emory Children's Center-Vaccine Research Clinic (ECC-VRC), Emory and community outreach, healthcare clinics, electronic health record messages, advertisements, and approved online recruitment methods.

Blood, nasal samples, and study data will be stored for the planned study tests. Remaining samples will be stored without information that directly identifies the infant, such as the infant's name or date of birth (de-identified), until the planned tests are complete and the study is closed. They will not be stored for unrelated future research. Study records will be kept as required by Emory, the study sponsor, and applicable rules.

• Clesrovimab (Biological), also known as Enflonsia™: Clesrovimab (ENFLONSIA™) is a commercially available product that is administered as part of standard-of-care RSV prevention.

Primary outcomes

• Geometric mean concentration (GMC) of serum RSV pre-fusion (preF) binding IgG antibodies [Baseline (Day 1), assigned early follow-up timepoint (Day 8 or Day 45) and Day 181]: RSV pre-fusion (preF) IgG binding antibodies in serum specimens will be quantified. Assay results will be reported as concentrations (arbitrary units per milliliter, AU/mL) derived from a calibrated standard curve. Serum RSV preF IgG concentrations will be summarized as geometric mean concentrations (GMC) at each study timepoint.
• Geometric mean concentration (GMC) of nasal RSV pre-fusion (preF) binding IgG antibodies [Baseline (Day 1), assigned early follow-up timepoint (Day 8 or Day 45) and Day 181]: RSV pre-fusion (preF) IgG binding antibodies in nasal specimens will be quantified. Assay results will be reported as concentrations (arbitrary units per milliliter, AU/mL) derived from a calibrated standard curve. For nasal specimens, RSV preF IgG concentrations will be normalized to total human IgG concentration. Normalized nasal antibody values will be summarized as GMC.
• Geometric mean titers (GMT) of serum RSV-A neutralizing antibodies [Baseline (Day 1), assigned early follow-up timepoint (Day 8 or Day 45) and Day 181]: Serum RSV neutralizing antibody titers will be measured using a microneutralization assay. Neutralizing antibody titers will be reported as reciprocal dilution EC50 titers (the serum dilution resulting in 50% neutralization) and summarized as geometric mean titers (GMTs).

Secondary outcomes

• Serum Geometric mean concentration (GMC) of clesrovimab [Baseline (Day 1), assigned early follow-up timepoint (Day 8 or Day 45) and Day 181]: Serum clesrovimab concentrations will be reported in concentration units and summarized as geometric mean concentrations (GMC) at each study timepoint.
• Urea-normalized GMC of clesrovimab in the nasal mucosa [Baseline (Day 1), assigned early follow-up timepoint (Day 8 or Day 45) and Day 181]: Clesrovimab concentrations will be normalized to urea concentration for nasal samples to account for variability in epithelial lining fluid dilution. Urea-normalized nasal clesrovimab concentrations will be summarized as GMC.

Sex: All, ages: any to 8 Months

Inclusion Criteria:

1. An infant who is <8 months of age at the time of immunization and born during or entering their first respiratory season.
2. The infant is in good health as established by medical history and investigator's discretion before entering the study. Chronic medical conditions are acceptable, provided that they are stable.
3. Written informed consent is obtained from the participant's parent(s)/legally authorized representative(s) (LAR) prior to performing any study specific procedures, including screening evaluations.
4. At least one parent/legally authorized representative of the subject is willing and able to maintain communication with the study site for the duration of the study.
5. Subject's parent(s)/legally authorized representative(s) is able to understand and comply with the requirements of the protocol including follow-up and illness visits as judged by the investigator.
6. Subject is available to complete the follow-up period, which will be approximately 6 months after receipt of the dose of study drug.

Exclusion Criteria:

1. Any fever (≥ 100.4°F \[≥ 38.0°C\], regardless of route) or acute illness within 3 days prior to enrollment.
2. Any current or expected receipt of immunosuppressive agents including systemic steroids (except for the use of topical steroids according to the judgment of the investigator).
3. Known immunodeficiency, including human immunodeficiency virus (HIV).
4. Any known allergy or hypersensitivity to immunoglobulin products.
5. Hypersensitivity, anaphylaxis, or seizures within 72 hours after any previous administration of a vaccine.
6. Receipt of polyclonal antibodies and/or plasma at any time prior to or planned during the study follow-up period.
7. Receipt of palivizumab, nirsevimab, or other RSV monoclonal antibody or any RSV vaccine at any time prior to or planned during the study.
8. Maternal receipt of an RSV vaccine during her pregnancy with the infant participant.
9. Use of any investigational product or non-registered product (drug or vaccine) other than the study product during the period starting 30 days before study product administration, or planned use during the study period.
10. Concurrent enrollment in another interventional study.
11. Any other condition that, in the judgment of the investigator, would be a risk to subject's safety and/or may interfere with study procedures or interpretation of results.
12. Unable to obtain baseline blood (minimum 0.5 mL) or nasal sample.

• Christina Rostad, MD, Principal investigator, Emory University