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

NCT ID: NCT03524118

Last Updated: 2025-01-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 183 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-09-20
• Study Completion Date: 2022-09-14

Brief Summary

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

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.

Conditions

Respiratory Tract Infection; Respiratory Syncytial Virus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Clesrovimab

Intervention Type: DRUG

Single ascending doses of clesrovimab will be administered via IM injection.

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.

Group Type: EXPERIMENTAL

Clesrovimab

Intervention Type: DRUG

Single ascending doses of clesrovimab will be administered via IM injection.

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.

Group Type: EXPERIMENTAL

Clesrovimab

Intervention Type: DRUG

Single ascending doses of clesrovimab will be administered via IM injection.

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.

Group Type: EXPERIMENTAL

Clesrovimab

Intervention Type: DRUG

Single ascending doses of clesrovimab will be administered via IM injection.

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.

Group Type: EXPERIMENTAL

Clesrovimab

Intervention Type: DRUG

Single ascending doses of clesrovimab will be administered via IM injection.

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.

Group Type: EXPERIMENTAL

Clesrovimab

Intervention Type: DRUG

Single ascending doses of clesrovimab will be administered via IM injection.

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.

Group Type: EXPERIMENTAL

Clesrovimab

Intervention Type: DRUG

Single ascending doses of clesrovimab will be administered via IM injection.

Placebo

Pre-term infants will receive placebo via IM injection.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo (0.9% sodium chloride \[NaCl\]) will be administered via IM injection.

Interventions

Clesrovimab

Single ascending doses of clesrovimab will be administered via IM injection.

Intervention Type: DRUG

Placebo

Placebo (0.9% sodium chloride \[NaCl\]) will be administered via IM injection.

Intervention Type: DRUG

Other Intervention Names

MK-1654

Eligibility Criteria

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

• Minimum Eligible Age: 2 Weeks
• Maximum Eligible Age: 8 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

Children's Hospital - Colorado ( Site 0067)

Aurora, Colorado, United States

Next Phase Research Alliance, LLC ( Site 0075)

Homestead, Florida, United States

Acevedo Clinical Research Associates ( Site 0025)

Miami, Florida, United States

Kapiolani Medical Center for Women and Children ( Site 0027)

Honolulu, Hawaii, United States

Cotton-O'Neil Clinical Research Center PediatricCare ( Site 0081)

Topeka, Kansas, United States

Children's Mercy Hospital ( Site 0037)

Kansas City, Missouri, United States

Dartmouth-Hitchcock Medical Center ( Site 0032)

Lebanon, New Hampshire, United States

SUNY Upstate Medical University Hospital ( Site 0029)

Syracuse, New York, United States

WakeMed Health and Hospitals ( Site 0033)

Raleigh, North Carolina, United States

Cincinnati Children's Hospital Medical Center ( Site 0031)

Cincinnati, Ohio, United States

Ohio Pediatric Research Association ( Site 0066)

Dayton, Ohio, United States

Coastal Pediatric Research ( Site 0028)

Charleston, South Carolina, United States

Tribe Clinical Research, LLC ( Site 0082)

Greenville, South Carolina, United States

University of Texas Medical Branch at Galveston ( Site 0039)

Galveston, Texas, United States

Tekton Research, Inc. ( Site 0026)

San Antonio, Texas, United States

Multicare Institute For Research And Innovation ( Site 0035)

Tacoma, Washington, United States

University of Wisconsin American Family Children's Hospital ( Site 0068)

Madison, Wisconsin, United States

Centro de Investigacion Clinica Bradford Hill ( Site 0103)

Santiago, Region M. de Santiago, Chile

Hospital La Florida ( Site 0050)

Santiago, Region M. de Santiago, Chile

Facultad Medicina Universidad de Chile ( Site 0104)

Santiago, Region M. de Santiago, Chile

Hospital Padre Hurtado ( Site 0102)

Santiago, Region M. de Santiago, Chile

Fundacion Hospital San Vicente de Paul ( Site 0097)

Medellín, Antioquia, Colombia

Universidad Pontificia Bolivariana - Clinica Universitaria Bolivariana ( Site 0098)

Medellín, Antioquia, Colombia

MedPlus Medicina Prepagada S.A. ( Site 0095)

Bogotá, Bogota D.C., Colombia

Fundacion Universitaria de Ciencias de la Salud - Sociedad de Cirugia ( Site 0099)

Bogotá, Bogota D.C., Colombia

Centro de Atención e Investigación Médica SAS - CAIMED CHIA ( Site 0100)

Chía, Cundinamarca, Colombia

Fundacion Valle del Lili ( Site 0090)

Cali, Valle del Cauca Department, Colombia

Chris Hani Baragwanath Academic Hospital ( Site 0262)

Johannesburg, Gauteng, South Africa

Tygerberg Hospital ( Site 0261)

Cape Town, Western Cape, South Africa

Seoul National University Hospital ( Site 0071)

Seoul, , South Korea

Severance Hospital Yonsei University Health System ( Site 0073)

Seoul, , South Korea

Samsung Medical Center ( Site 0072)

Seoul, , South Korea

Hospital Clinico Universitario de Santiago ( Site 0241)

Santiago de Compostela, La Coruna, Spain

Hospital Universitario La Paz ( Site 0242)

Madrid, , Spain

Countries

United States; Chile; Colombia; South Africa; South Korea; Spain

References

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 Trial of a Half-life Extended Respiratory Syncytial Virus Neutralizing Antibody, Clesrovimab, in Healthy Preterm and Full-term Infants. J Infect Dis. 2025 Mar 17;231(3):e478-e487. doi: 10.1093/infdis/jiae581.

Reference Type: RESULT

PMID: 39601265 (View on PubMed)

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 Antidrug Antibodies in a Phase 1b/2a Infant Clesrovimab Trial Are Associated With RSV Exposure Beyond Day 150. J Infect Dis. 2025 Mar 17;231(3):e488-e496. doi: 10.1093/infdis/jiae582.

Reference Type: RESULT

PMID: 39590882 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

https://www.merckclinicaltrials.com

Merck Clinical Trials Information

Other Identifiers

MK-1654-002

Identifier Type: OTHER

Identifier Source: secondary_id

2017-005062-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

1654-002

Identifier Type: -

Identifier Source: org_study_id