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

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

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.

Study Overview

• Status: Completed
• Conditions: Respiratory Syncytial Virus; Respiratory Tract Infection
• Intervention / Treatment: Drug: Clesrovimab; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 183
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Chile
  • Region M. De Santiago
    • Santiago, Region M. De Santiago, Chile, 7650698
      • Centro de Investigacion Clinica Bradford Hill ( Site 0103)
    • Santiago, Region M. De Santiago, Chile, 8242238
      • Hospital La Florida ( Site 0050)
    • Santiago, Region M. De Santiago, Chile, 8380453
      • Facultad Medicina Universidad de Chile ( Site 0104)
    • Santiago, Region M. De Santiago, Chile, 8880465
      • Hospital Padre Hurtado ( Site 0102)
• Colombia
  • Antioquia
    • Medellin, Antioquia, Colombia, 050010
      • Fundacion Hospital San Vicente de Paul ( Site 0097)
    • Medellin, Antioquia, Colombia, 050036
      • Universidad Pontificia Bolivariana - Clinica Universitaria Bolivariana ( Site 0098)
  • Cundinamarca
    • Chia, Cundinamarca, Colombia, 250001
      • Centro de Atención e Investigación Médica SAS - CAIMED CHIA ( Site 0100)
  • Distrito Capital De Bogota
    • Bogota, Distrito Capital De Bogota, Colombia, 110221
      • MedPlus Medicina Prepagada S.A. ( Site 0095)
    • Bogota, Distrito Capital De Bogota, Colombia, 111411
      • Fundacion Universitaria de Ciencias de la Salud - Sociedad de Cirugia ( Site 0099)
  • Valle Del Cauca
    • Cali, Valle Del Cauca, Colombia, 760032
      • Fundacion Valle del Lili ( Site 0090)
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital ( Site 0071)
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital Yonsei University Health System ( Site 0073)
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center ( Site 0072)
• South Africa
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 2013
      • Chris Hani Baragwanath Academic Hospital ( Site 0262)
  • Western Cape
    • Cape Town, Western Cape, South Africa, 7505
      • Tygerberg Hospital ( Site 0261)
• Spain
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz ( Site 0242)
  • La Coruna
    • Santiago de Compostela, La Coruna, Spain, 15706
      • Hospital Clinico Universitario de Santiago ( Site 0241)
• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital - Colorado ( Site 0067)
  • Florida
    • Homestead, Florida, United States, 33030
      • Next Phase Research Alliance, LLC ( Site 0075)
    • Miami, Florida, United States, 33142
      • Acevedo Clinical Research Associates ( Site 0025)
  • Hawaii
    • Honolulu, Hawaii, United States, 96826
      • Kapiolani Medical Center for Women and Children ( Site 0027)
  • Kansas
    • Topeka, Kansas, United States, 66604
      • Cotton-O'Neil Clinical Research Center PediatricCare ( Site 0081)
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Children's Mercy Hospital ( Site 0037)
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03766
      • Dartmouth-Hitchcock Medical Center ( Site 0032)
  • New York
    • Syracuse, New York, United States, 13210
      • SUNY Upstate Medical University Hospital ( Site 0029)
  • North Carolina
    • Raleigh, North Carolina, United States, 27610
      • WakeMed Health and Hospitals ( Site 0033)
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center ( Site 0031)
    • Dayton, Ohio, United States, 45414
      • Ohio Pediatric Research Association ( Site 0066)
  • South Carolina
    • Charleston, South Carolina, United States, 29414
      • Coastal Pediatric Research ( Site 0028)
    • Greenville, South Carolina, United States, 29607
      • Tribe Clinical Research, LLC ( Site 0082)
  • Texas
    • Galveston, Texas, United States, 77555
      • University of Texas Medical Branch at Galveston ( Site 0039)
    • San Antonio, Texas, United States, 78240
      • Tekton Research, Inc. ( Site 0026)
  • Washington
    • Tacoma, Washington, United States, 98405
      • Multicare Institute For Research And Innovation ( Site 0035)
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin American Family Children's Hospital ( Site 0068)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 weeks to 8 months (Child)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Triple

Number of Arms

8

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Madhi SA, Simoes EAF, Acevedo A, Novoa Pizarro JM, Shepard JS, Railkar RA, Cao X, Maas BM, Zang X, Krick A, Roadcap B, Vora KA, Aliprantis AO, Lee AW, Sinha A. A Phase 1b/2a Single Ascending Dose Study of a Half-life Extended RSV Neutralizing Antibody, Clesrovimab, in Healthy Preterm and Full-term Infants. J Infect Dis. 2024 Nov 27:jiae581. doi: 10.1093/infdis/jiae581. Online ahead of print.
• Thambi N, Phuah JY, Staupe RP, Tobias LM, Cao Y, McKelvey T, Railkar RA, Aliprantis AO, Arriola CS, Maas BM, Vora KA. Development of high titer anti-drug antibodies in a Phase 1b/2a infant clesrovimab trial are associated with RSV exposure beyond day 150. J Infect Dis. 2024 Nov 26:jiae582. doi: 10.1093/infdis/jiae582. Online ahead of print.

Helpful Links

• Merck Clinical Trials Information

Study record dates

Study Major Dates

• Study Start (Actual): September 20, 2018
• Primary Completion (Actual): September 14, 2022
• Study Completion (Actual): September 14, 2022

Study Registration Dates

• First Submitted: May 11, 2018
• First Submitted That Met QC Criteria: May 11, 2018
• First Posted (Actual): May 14, 2018

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 6, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Diseases; Respiratory Tract Infections
• Other Study ID Numbers: 1654-002; MK-1654-002 (Other Identifier: Merck Protocol Number); 2017-005062-21 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No