A Phase 2b/3 Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of MK-1654 in Healthy Pre-Term and Full-Term Infants

The primary objective of this study is to evaluate the **efficacy** of MK-1654 compared to placebo by assessing the incidence of **respiratory syncytial virus** (RSV)-associated medically attended lower respiratory infection (MALRI) in both outpatient and inpatient settings from Days 1 through 150 postdose. Additionally, the study aims to evaluate the safety and tolerability of MK-1654 compared to placebo by assessing the proportion of participants experiencing adverse events (AEs). This is clinically relevant as it addresses the prevention of RSV, a significant cause of respiratory infections in infants, potentially reducing the burden of disease and improving patient outcomes.

Secondary objectives include:

• Evaluating the efficacy of MK-1654 compared to placebo by assessing the incidence of RSV-associated hospitalization from Days 1 through 150 postdose.
• Estimating the efficacy of MK-1654 compared to placebo by assessing the incidence of RSV-associated MALRI, both outpatient and inpatient, from Days 1 through 180 postdose.

The clinical trial for the **prevention of RSV** involves a total of 2710 participants. The study population comprises both male and female infants, including early or moderate pre-term infants (≥29 to 34 weeks and 6 days gestational age) and late pre-term or full-term infants (≥35 weeks gestational age). Participants are selected based on their chronological age, which ranges from birth up to 1 year, and they must be entering their first RSV season at the time of obtaining documented informed consent. The trial includes a vulnerable population, as it involves infants. Participants are required to be healthy, and for those in South Korea, a minimum weight of ≥2 kg is specified. The trial does not specify any particular lifestyle considerations such as diet or physical activity for the participants.

The clinical trial is designed as a **randomized**, **double-blind**, **placebo-controlled** study to evaluate the efficacy and safety of MK-1654 in healthy pre-term and full-term infants for the prevention of **respiratory syncytial virus** (RSV). The trial is structured in two phases, 2b and 3, with the primary objective of assessing the incidence of RSV-associated medically attended lower respiratory infection (MALRI) from Days 1 through 150 postdose. The trial also aims to evaluate the safety and tolerability of MK-1654 by monitoring adverse events (AEs) in comparison to a placebo. The study is expected to conclude by September 2024, with recruitment having commenced in October 2022.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as gestational age and chronological age. The trial includes follow-up visits to monitor the incidence of RSV-associated MALRI and any adverse events. The end-of-study visit will conclude the participant's involvement, ensuring all data is collected and any final assessments are completed. The expected length of participant involvement is approximately 150 days postdose, with conditions for early termination including the occurrence of serious adverse events or withdrawal of consent.

Inclusion criteria specify that participants must be healthy infants, either early or moderate pre-term (≥29 to 34 weeks and 6 days gestational age) or late pre-term/full-term (≥35 weeks gestational age). For the phase 2b cohort, infants must be over 2 weeks old and entering their first RSV season, while the phase 3 cohort includes infants from birth up to 1 year old. The primary endpoints include the percentage of participants with RSV-associated MALRI and various adverse events, while secondary endpoints focus on RSV-associated hospitalization rates. The trial's methodology ensures rigorous assessment of MK-1654's efficacy and safety, contributing valuable data to the field of RSV prevention in infants.

The clinical trial involves the evaluation of **MK-1654**, an investigational medication developed by **MERCK & CO. INC.**. MK-1654 is a protein-based therapeutic agent, classified under the category of "Protein - Other." The pharmaceutical form, dosage, route, and frequency of administration for MK-1654 are not specified in the provided data. The primary objective of the trial is to assess the efficacy and safety of MK-1654 in preventing respiratory syncytial virus (RSV)-associated medically attended lower respiratory infections in healthy pre-term and full-term infants.

The study also includes a **placebo** as a comparator treatment. The placebo is utilized to provide a control group for evaluating the efficacy and safety of MK-1654. The placebo is administered in a manner consistent with the experimental treatment, although specific details regarding its pharmaceutical form, dosage, route, and frequency of administration are not provided in the data.

Additionally, a **saline solution** is mentioned as another non-experimental treatment in the study. The saline solution, produced by **B.BRAUN MELSUNGEN AG**, serves as a standard-of-care therapy. It is a chemically derived product, although specific details regarding its administration and dosing schedule are not included in the provided information.

Participant compliance with the dosing regimen and administration schedule is monitored throughout the trial to ensure the integrity of the study results. The trial is conducted in a double-blind, randomized, placebo-controlled manner to minimize bias and ensure the reliability of the findings.

The efficacy of MK-1654 in the clinical trial will be assessed by evaluating the incidence of **respiratory syncytial virus (RSV)**-associated medically attended lower respiratory infection (MALRI) in both outpatient and inpatient settings. This assessment will occur from Days 1 through 150 postdose. The primary endpoints include the percentage of participants with RSV-associated MALRI, solicited injection-site adverse events (AEs), fever, solicited systemic AEs, anaphylaxis/hypersensitivity AEs of special interest (AESI), rash AESI, nonserious AEs, and serious adverse events (SAEs). Secondary endpoints focus on the percentage of participants with RSV-associated hospitalization and RSV-associated MALRI.