Safety, Tolerability, and Pharmacokinetics of Clesrovimab (MK-1654) in Infants (MK-1654-002)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and incidence of anti-drug antibodies (ADAs) of single ascending doses of clesrovimab in healthy pre-term (born at 29 to 35 weeks gestational age) and full-term (born at >35 weeks gestational age) infants. Participants will be randomized into 1 of 4 dose escalation panels (Panels A to D); an additional panel (Panel E) of full-term infants will receive the same dose as Panel D. Key safety and tolerability variables will be reviewed after each dose panel prior to administering the next-highest dose.

Detailed Description
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Participants in Dose Panels A, B, C, D1, and E1 will be followed for up to 365 days. After protocol Amendment 4 (AM4), participants in Dose Panels D2 and E2 will be followed for up to 545 days.

Official Title
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A Double-blind, Randomized, Placebo-controlled, Single Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of MK-1654 in Pre-Term and Full-Term Infants

Conditions
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Respiratory Tract Infection, Respiratory Syncytial Virus

Intervention / Treatment
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* Drug: Clesrovimab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: is healthy, based on screening safety laboratory, medical history, and physical examination results is a pre-term infant (born at 29 weeks to 35 weeks gestational age [inclusive]) or a full-term infant (born at over 35 weeks gestational age), as confirmed in medical records weighs ≥2 kg at screening Exclusion Criteria: has been recommended to receive palivizumab per local standard of care has ≥1 documented out-of-range safety laboratory results (adjusted for age) at the time of screening has a known hypersensitivity to any component of the respiratory syncytial virus (RSV) monoclonal antibody has a history of congenital or acquired immunodeficiency (e.g., splenomegaly) has documented human immunodeficiency virus (HIV) infection, hepatitis B (HBsAg positive), or hepatitis C (HCV ribonucleic acid [RNA] positive) has known history of functional or anatomic asplenia has a diagnosis of failure to thrive within 14 days of screening has known or history of a coagulation disorder contraindicating intramuscular injection has received or is expected to receive blood products (except irradiated platelets) within 3 months prior to enrollment has prior known documented RSV infection has hemodynamically significant congenital heart disease has chronic lung disease of prematurity requiring ongoing medical therapy has a history or current evidence of any condition, therapy, lab abnormality or other circumstance that, in the opinion of the investigator, might expose the participant to undue risk by participating in the study, confound the results of the study, or interfere with the participant's participation for the full duration of the study has any history of malignancy prior to randomization if any of the following apply, the Day 1 visit may be rescheduled for a time when these criteria are not met: has had a recent febrile illness (rectal temperature 38.1°C [100.5°F] or higher or axillary temperature 37.8°C [100.0°F] or higher) within 72 hours pre-dose is not up-to-date on required vaccinations per local pediatric vaccine schedule at time of screening has received inactivated or component vaccines (eg, influenza, hepatitis B) less than 14 days pre-dose has received live, attenuated, non-study licensed pediatric vaccines (e.g., Bacillus Calmette-Guerin vaccine) less than 30 days pre-dose has received any prior vaccine or monoclonal antibody (mAb) 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 prior to first dose administration or while participating in this current study (participants enrolled in observational studies may be included and will be reviewed on a case-by-case basis for approval by the Sponsor) has enrolled previously in this study and been discontinued participant's mother participated in a RSV vaccine clinical study while pregnant and participant is ≤3 months of chronological age is unable to provide blood sample at screening cannot be adequately followed for safety according to the protocol plan has a parent/legally acceptable representative who is unlikely to adhere to study procedures, keep appointments, or is planning to relocate during the study is, or has, an immediate family member (eg, spouse, parent/guardian, sibling, or child) who is directly involved with the study at the site or with the Sponsor

Ages Eligible for Study
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Minimum Age: 2 Weeks
Maximum Age: 8 Months

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: Sequential Assignment
Interventional Model Description: Single ascending dose
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Panel A: Pre-term clesrovimab Dose 1<br>Pre-term infants will receive clesrovimab Dose 1 via intramuscular (IM) injection and will be followed for up to 365 days. | Drug: Clesrovimab<br>* Single ascending doses of clesrovimab will be administered via IM injection.<br>* Other names: MK-1654;|
| Experimental: Panel B: Pre-term clesrovimab Dose 2<br>Pre-term infants will receive clesrovimab Dose 2 via IM injection and will be followed for up to 365 days. | Drug: Clesrovimab<br>* Single ascending doses of clesrovimab will be administered via IM injection.<br>* Other names: MK-1654;|
| Experimental: Panel C: Pre-term clesrovimab Dose 3<br>Pre-term infants will receive clesrovimab Dose 3 via IM injection and will be followed for up to 365 days. | Drug: Clesrovimab<br>* Single ascending doses of clesrovimab will be administered via IM injection.<br>* Other names: MK-1654;|
| Experimental: Panel D1: Pre-term clesrovimab Dose 4<br>Pre-term infants enrolled prior to AM4 will receive clesrovimab Dose 4 via IM injection and will be followed for up to 365 days. | Drug: Clesrovimab<br>* Single ascending doses of clesrovimab will be administered via IM injection.<br>* Other names: MK-1654;|
| Experimental: Panel D2: Pre-term clesrovimab Dose 4<br>Pre-term infants enrolled after AM4 will receive clesrovimab Dose 4 via IM injection and will be followed for up to 545 days. | Drug: Clesrovimab<br>* Single ascending doses of clesrovimab will be administered via IM injection.<br>* Other names: MK-1654;|
| Experimental: Panel E1: Full-term clesrovimab Dose 4<br>Full-term infants enrolled prior to AM4 will receive clesrovimab Dose 4 via IM injection and will be followed for up to 365 days. | Drug: Clesrovimab<br>* Single ascending doses of clesrovimab will be administered via IM injection.<br>* Other names: MK-1654;|
| Experimental: Panel E2: Full-term clesrovimab Dose 4<br>Full-term infants enrolled after AM4 will receive clesrovimab Dose 4 via IM injection and will be followed for up to 545 days. | Drug: Clesrovimab<br>* Single ascending doses of clesrovimab will be administered via IM injection.<br>* Other names: MK-1654;|
| Placebo Comparator: Placebo<br>Pre-term infants will receive placebo via IM injection. | Drug: Placebo<br>* Placebo (0.9% sodium chloride [NaCl]) will be administered via IM injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Experienced At Least One Solicited Injection Site Adverse Event (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. Solicited injection site AEs were monitored from Day 1 to Day 5. | Up to Day 5 | 
| Percentage of Participants Who Experienced At Least One Solicited Systemic Adverse Event (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. Solicited systemic AEs were monitored from Day 1 to Day 5. | Up to Day 5 | 
| Percentage of Participants Who Experienced At Least One Serious Adverse Event (SAE) | An SAE is any untoward medical occurrence that, at any dose, results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant injury/incapacity; is a congenital anomaly/birth defect; or is an other important medical event. | Up to Day 545 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Serum-Concentration Time Curve From Zero to Infinity (AUC0-∞) | AUC0-∞ is a measure of the extrapolated mean concentration in serum from dosing to infinity. | At designated time points (up to 1 year post-dose) | 
| Maximum Serum Concentration (Cmax) of Clesrovimab | Cmax is the highest observed serum drug concentration. | At designated time points (up to 1 year post-dose) | 
| Time to Maximum Serum Concentration (Tmax) of Clesrovimab | Tmax is the time taken to reach the maximum observed plasma (Cmax) concentration of Clesrovimab. | At designated time points (up to 1 year post-dose) | 
| Apparent Terminal Half-life (t1/2) of Clesrovimab | t1/2 is the time required for 50% of drug to be cleared from serum. | At designated time points (up to 1 year post-dose) | 
| Serum Concentration of Clesrovimab on Day 7 (C7days) | Serum concentration of clesrovimab was measured on Day 7. | Day 7 | 
| Serum Concentration of Clesrovimab on Day 14 (C14days) | Serum concentration of clesrovimab was measured on Day 14. | Day 14 | 
| Serum Concentration of Clesrovimab on Day 90 (C90days) | Serum concentration of clesrovimab was measured on Day 90. | Day 90 | 
| Serum Concentration of Clesrovimab on Day 150 (C150days) | Serum concentration of clesrovimab was measured on Day 150. | Day 150 | 
| Serum Concentration of Clesrovimab on Day 365 (C365days) | Serum concentration of clesrovimab was measured on Day 365. | Day 365 | 
| Number of Participants With Positive Titer of Anti-Drug Antibodies (ADAs) for Clesrovimab: Panels A, B, C, D1, D2, E1, and E2 | ADA was assessed at 2 or 3 of the following timepoints for each participant: Days 14, 90, 150, 365 and 545. ADA status for each participant was determined across the timepoints assessed. The definitions of the categories are as follows: (1) ADA Negative: participants whose ADA results were negative at all timepoints measured; (2) Non-treatment emergent positive: participants whose ADA result was positive only at baseline or if postdose titer increased by less than 2-fold relative to the baseline titer; (3) Positive response to MK-1654: participants whose ADA result was negative at baseline and positive at one or more postdose timepoints or participants whose ADA result was positive at baseline and postdose titer increased by greater than or equal to 2-fold relative to the baseline titer. | Days 14, 90, 150, 365 and 545 |