Efficacy and Safety of Clesrovimab (MK-1654) in Infants (MK-1654-004)

Study Overview
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Brief Summary
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The primary objectives of this phase 2b/3 double-blind, randomized, placebo-controlled study are to evaluate the efficacy and safety of clesrovimab in healthy pre-term and full-term infants. It is hypothesized that clesrovimab will reduce the incidence of respiratory syncytial virus (RSV)-associated medically attended lower respiratory infection (MALRI) from Days 1 through 150 postdose compared to placebo.

Official Title
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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

Conditions
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Respiratory Syncytial Virus Infection

Intervention / Treatment
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* Biological: Clesrovimab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Is a healthy male or female who is an early or moderate pre-term infant (≥29 to 34 weeks and 6 days gestational age) or a late pre-term or full-term infant (≥35 weeks gestational age) For the phase 2b cohort only: Has a chronological age >2 weeks of age up to 1 year and is entering their first RSV season at the time of obtaining documented informed consent. For the phase 3 cohort only: Has a chronological age from birth up to 1 year and is entering their first RSV season at the time of obtaining documented informed consent. For participants in South Korea only: Weighs ≥2 kg Key Exclusion Criteria: Is recommended to receive palivizumab per local guidelines or professional society recommendations. Has known hypersensitivity to any component of clesrovimab Has a bleeding disorder contraindicating IM administration Has had a recent illness with rectal temperature ≥100.5°F (≥38.1°C) or axillary temperature ≥100.0°F (≥37.8°C) within 72 hours predose Has received any vaccine or monoclonal antibody for the prevention of RSV Is currently participating in or has participated in an interventional clinical study with an investigational compound or device at any time before first dose administration or while participating in this study

Ages Eligible for Study
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Maximum Age: 1 Year

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Clesrovimab<br>Participants receive a single intramuscular (IM) administration of clesrovimab on Day 1. | Biological: Clesrovimab<br>* Clesrovimab solution<br>* Other names: MK-1654;|
| Placebo Comparator: Placebo<br>Participants receive a single IM administration of placebo on Day 1. | Drug: Placebo<br>* Placebo (0.9% sodium chloride [NaCL]) solution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants with RSV-associated MALRI | Outpatient and inpatient MALRI is defined as the presence of the following in a clinical setting: 1) cough or difficulty breathing; AND 2) 1 or more of wheezing, chest wall in-drawing/retraction, rales/crackles, hypoxemia, tachypnea, or dehydration; AND 3) RSV-positive reverse transcriptase polymerase chain reaction (RT-PCR) nasopharyngeal sample. | From Day 1 (postdose) to Day 150 | 
| Percentage of participants with solicited injection-site adverse events (AEs) | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants with solicited injection-site AEs (i.e., redness/erythema, swelling, and pain/tenderness) will be reported. | From Day 1 (postdose) to Day 5 | 
| Percentage of participants with fever | Fever is defined as as rectal temperature ≥102.2°F (≥39.0°C) or axillary temperature ≥101.7°F (≥38.7°C). The percentage of participants with fever will be reported. | From Day 1 (postdose) to Day 5 | 
| Percentage of participants with solicited systemic AEs | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants with solicited systemic AEs (i.e., irritability, drowsiness, and appetite lost) will be reported. | From Day 1 (postdose) to Day 5 | 
| Percentage of participants with anaphylaxis/hypersensitivity AE of special interest (AESI) | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants with anaphylaxis/hypersensitivity will be reported. | From Day 1 (postdose) to Day 42 | 
| Percentage of participants with rash AESI | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants with rash will be reported. | From Day 1 (postdose) to Day 42 | 
| Percentage of participants with ≥1 nonserious AE | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. | From Day 1 (postdose) to Day 42 | 
| Percentage of participants with serious adverse events (SAEs) | An SAE is any untoward medical occurrence that results in death; is life-threatening; required inpatient hospitalization/prolongs existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or other important medical event. The percentage of participants with SAEs will be reported. | Up to Day 515 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants with RSV-associated hospitalization | RSV-associated hospitalization is defined as a hospital admission for respiratory illness AND RSV-positive RT-PCR nasopharyngeal sample. | From Day 1 (postdose) to Day 150 | 
| Percentage of participants with RSV-associated MALRI | Outpatient and inpatient MALRI is defined as the presence of the following in a clinical setting: 1) cough or difficulty breathing; AND 2) 1 or more of wheezing, chest wall in-drawing/retraction, rales/crackles, hypoxemia, tachypnea, or dehydration; AND 3) RSV-positive RT-PCR nasopharyngeal sample. | From Day 1 (postdose) to Day 180 |