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

NCT03524118 | Completed Phase 1 Results FDA Drug

• 3 other identifiers: 1654-002MK-1654-0022017-005062-21
• Study Type: interventional
• Target: 183
• Locations: 6 countries
• Sites: 34

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.

Conditions

Respiratory Tract Infection; Respiratory Syncytial Virus

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (10)

• Area Under the Serum-Concentration Time Curve From Zero to Infinity (AUC0-∞)

  At designated time points (up to 1 year post-dose)

• Maximum Serum Concentration (Cmax) of Clesrovimab

  At designated time points (up to 1 year post-dose)

• Time to Maximum Serum Concentration (Tmax) of Clesrovimab

  At designated time points (up to 1 year post-dose)

• Apparent Terminal Half-life (t1/2) of Clesrovimab

  At designated time points (up to 1 year post-dose)

• Serum Concentration of Clesrovimab on Day 7 (C7days)

  Day 7

Study Arms (8)

Panel A: Pre-term clesrovimab Dose 1

EXPERIMENTAL

Pre-term infants will receive clesrovimab Dose 1 via intramuscular (IM) injection and will be followed for up to 365 days.

Drug: Clesrovimab

Panel B: Pre-term clesrovimab Dose 2

EXPERIMENTAL

Pre-term infants will receive clesrovimab Dose 2 via IM injection and will be followed for up to 365 days.

Drug: Clesrovimab

Panel C: Pre-term clesrovimab Dose 3

EXPERIMENTAL

Pre-term infants will receive clesrovimab Dose 3 via IM injection and will be followed for up to 365 days.

Drug: Clesrovimab

Panel D1: Pre-term clesrovimab Dose 4

EXPERIMENTAL

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

Panel D2: Pre-term clesrovimab Dose 4

EXPERIMENTAL

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

Panel E1: Full-term clesrovimab Dose 4

EXPERIMENTAL

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

Panel E2: Full-term clesrovimab Dose 4

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

Pre-term infants will receive placebo via IM injection.

Drug: Placebo

Interventions

Clesrovimab DRUG

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

Also known as: MK-1654

Panel A: Pre-term clesrovimab Dose 1; Panel B: Pre-term clesrovimab Dose 2; Panel C: Pre-term clesrovimab Dose 3; Panel D1: Pre-term clesrovimab Dose 4; Panel D2: Pre-term clesrovimab Dose 4; Panel E1: Full-term clesrovimab Dose 4; Panel E2: Full-term clesrovimab Dose 4

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 2 Weeks - 8 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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:

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (34)

Children's Hospital - Colorado ( Site 0067)

Aurora, Colorado, 80045, United States

Location

Next Phase Research Alliance, LLC ( Site 0075)

Homestead, Florida, 33030, United States

Location

Acevedo Clinical Research Associates ( Site 0025)

Miami, Florida, 33142, United States

Location

Kapiolani Medical Center for Women and Children ( Site 0027)

Honolulu, Hawaii, 96826, United States

Location

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

Topeka, Kansas, 66604, United States

Location

Children's Mercy Hospital ( Site 0037)

Kansas City, Missouri, 64108, United States

Location

Dartmouth-Hitchcock Medical Center ( Site 0032)

Lebanon, New Hampshire, 03766, United States

Location

SUNY Upstate Medical University Hospital ( Site 0029)

Syracuse, New York, 13210, United States

Location

WakeMed Health and Hospitals ( Site 0033)

Raleigh, North Carolina, 27610, United States

Location

Cincinnati Children's Hospital Medical Center ( Site 0031)

Cincinnati, Ohio, 45229, United States

Location

Ohio Pediatric Research Association ( Site 0066)

Dayton, Ohio, 45414, United States

Location

Coastal Pediatric Research ( Site 0028)

Charleston, South Carolina, 29414, United States

Location

Tribe Clinical Research, LLC ( Site 0082)

Greenville, South Carolina, 29607, United States

Location

University of Texas Medical Branch at Galveston ( Site 0039)

Galveston, Texas, 77555, United States

Location

Tekton Research, Inc. ( Site 0026)

San Antonio, Texas, 78240, United States

Location

Multicare Institute For Research And Innovation ( Site 0035)

Tacoma, Washington, 98405, United States

Location

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

Madison, Wisconsin, 53792, United States

Location

Centro de Investigacion Clinica Bradford Hill ( Site 0103)

Santiago, Region M. de Santiago, 7650698, Chile

Location

Hospital La Florida ( Site 0050)

Santiago, Region M. de Santiago, 8242238, Chile

Location

Facultad Medicina Universidad de Chile ( Site 0104)

Santiago, Region M. de Santiago, 8380453, Chile

Location

Hospital Padre Hurtado ( Site 0102)

Santiago, Region M. de Santiago, 8880465, Chile

Location

Fundacion Hospital San Vicente de Paul ( Site 0097)

Medellín, Antioquia, 050010, Colombia

Location

Universidad Pontificia Bolivariana - Clinica Universitaria Bolivariana ( Site 0098)

Medellín, Antioquia, 050036, Colombia

Location

MedPlus Medicina Prepagada S.A. ( Site 0095)

Bogotá, Bogota D.C., 110221, Colombia

Location

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

Bogotá, Bogota D.C., 111411, Colombia

Location

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

Chía, Cundinamarca, 250001, Colombia

Location

Fundacion Valle del Lili ( Site 0090)

Cali, Valle del Cauca Department, 760032, Colombia

Location

Chris Hani Baragwanath Academic Hospital ( Site 0262)

Johannesburg, Gauteng, 2013, South Africa

Location

Tygerberg Hospital ( Site 0261)

Cape Town, Western Cape, 7505, South Africa

Location

Seoul National University Hospital ( Site 0071)

Seoul, 03080, South Korea

Location

Severance Hospital Yonsei University Health System ( Site 0073)

Seoul, 03722, South Korea

Location

Samsung Medical Center ( Site 0072)

Seoul, 06351, South Korea

Location

Hospital Clinico Universitario de Santiago ( Site 0241)

Santiago de Compostela, La Coruna, 15706, Spain

Location

Hospital Universitario La Paz ( Site 0242)

Madrid, 28046, Spain

Location

Related Publications (2)

• 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.

  PMID: 39601265 RESULT

• 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.

  PMID: 39590882 RESULT

Related Links

• Merck Clinical Trials Information

MeSH Terms

Conditions

Respiratory Tract Infections

Interventions

MK-1654

Condition Hierarchy (Ancestors)

Infections; Respiratory Tract Diseases

Results Point of Contact

• Title: Clinical Trials Disclosure
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single ascending dose

Study Record Dates

• First Submitted: May 11, 2018
• First Posted: May 14, 2018
• Study Start: September 20, 2018
• Primary Completion: September 14, 2022
• Study Completion: September 14, 2022
• Last Updated: January 14, 2025
• Results First Posted: November 29, 2023

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share

Locations

CO (6); KR (3); US (17); CL (4); ZA (2); ES (2)