Clinical trial NCT03524118: Safety, Tolerability, and Pharmacokinetics of Clesrovimab (MK-1654) in Infants (MK-1654-002)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Respiratory Tract Infection
Respiratory Syncytial Virus
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2018-05-14
Enrollment: 183
Sex: ALL
Minimum age (years): 2
Maximum age (years): 8
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Single ascending dose
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: Percentage of Participants Who Experienced At Least One Solicited Injection Site Adverse Event (AE)
timeFrame: Up to Day 5
measure: Percentage of Participants Who Experienced At Least One Solicited Systemic Adverse Event (AE)
timeFrame: Up to Day 5
measure: Percentage of Participants Who Experienced At Least One Serious Adverse Event (SAE)
timeFrame: Up to Day 545
Secondary outcomes:
measure: Area Under the Serum-Concentration Time Curve From Zero to Infinity (AUC0-∞)
timeFrame: At designated time points (up to 1 year post-dose)
measure: Maximum Serum Concentration (Cmax) of Clesrovimab
timeFrame: At designated time points (up to 1 year post-dose)
measure: Time to Maximum Serum Concentration (Tmax) of Clesrovimab
timeFrame: At designated time points (up to 1 year post-dose)
measure: Apparent Terminal Half-life (t1/2) of Clesrovimab
timeFrame: At designated time points (up to 1 year post-dose)
measure: Serum Concentration of Clesrovimab on Day 7 (C7days)
timeFrame: Day 7
measure: Serum Concentration of Clesrovimab on Day 14 (C14days)
timeFrame: Day 14
measure: Serum Concentration of Clesrovimab on Day 90 (C90days)
timeFrame: Day 90
measure: Serum Concentration of Clesrovimab on Day 150 (C150days)
timeFrame: Day 150
measure: Serum Concentration of Clesrovimab on Day 365 (C365days)
timeFrame: Day 365
measure: Number of Participants With Positive Titer of Anti-Drug Antibodies (ADAs) for Clesrovimab: Panels A, B, C, D1, D2, E1, and E2
timeFrame: Days 14, 90, 150, 365 and 545
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Children's Hospital - Colorado ( Site 0067)
state: Colorado
city: Homestead
country: United States
facility: Next Phase Research Alliance, LLC ( Site 0075)
state: Florida
city: Miami
country: United States
facility: Acevedo Clinical Research Associates ( Site 0025)
state: Florida
city: Honolulu
country: United States
facility: Kapiolani Medical Center for Women and Children ( Site 0027)
state: Hawaii
city: Topeka
country: United States
facility: Cotton-O'Neil Clinical Research Center PediatricCare ( Site 0081)
state: Kansas
city: Kansas City
country: United States
facility: Children's Mercy Hospital ( Site 0037)
state: Missouri
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center ( Site 0032)
state: New Hampshire
city: Syracuse
country: United States
facility: SUNY Upstate Medical University Hospital ( Site 0029)
state: New York
city: Raleigh
country: United States
facility: WakeMed Health and Hospitals ( Site 0033)
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center ( Site 0031)
state: Ohio
city: Dayton
country: United States
facility: Ohio Pediatric Research Association ( Site 0066)
state: Ohio
city: Charleston
country: United States
facility: Coastal Pediatric Research ( Site 0028)
state: South Carolina
city: Greenville
country: United States
facility: Tribe Clinical Research, LLC ( Site 0082)
state: South Carolina
city: Galveston
country: United States
facility: University of Texas Medical Branch at Galveston ( Site 0039)
state: Texas
city: San Antonio
country: United States
facility: Tekton Research, Inc. ( Site 0026)
state: Texas
city: Tacoma
country: United States
facility: Multicare Institute For Research And Innovation ( Site 0035)
state: Washington
city: Madison
country: United States
facility: University of Wisconsin American Family Children's Hospital ( Site 0068)
state: Wisconsin
city: Santiago
country: Chile
facility: Centro de Investigacion Clinica Bradford Hill ( Site 0103)
state: Region M. De Santiago
city: Santiago
country: Chile
facility: Hospital La Florida ( Site 0050)
state: Region M. De Santiago
city: Santiago
country: Chile
facility: Facultad Medicina Universidad de Chile ( Site 0104)
state: Region M. De Santiago
city: Santiago
country: Chile
facility: Hospital Padre Hurtado ( Site 0102)
state: Region M. De Santiago
city: Medellin
country: Colombia
facility: Fundacion Hospital San Vicente de Paul ( Site 0097)
state: Antioquia
city: Medellin
country: Colombia
facility: Universidad Pontificia Bolivariana - Clinica Universitaria Bolivariana ( Site 0098)
state: Antioquia
city: Chia
country: Colombia
facility: Centro de Atención e Investigación Médica SAS - CAIMED CHIA ( Site 0100)
state: Cundinamarca
city: Bogota
country: Colombia
facility: MedPlus Medicina Prepagada S.A. ( Site 0095)
state: Distrito Capital De Bogota
city: Bogota
country: Colombia
facility: Fundacion Universitaria de Ciencias de la Salud - Sociedad de Cirugia ( Site 0099)
state: Distrito Capital De Bogota
city: Cali
country: Colombia
facility: Fundacion Valle del Lili ( Site 0090)
state: Valle Del Cauca
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital ( Site 0071)
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System ( Site 0073)
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center ( Site 0072)
city: Johannesburg
country: South Africa
facility: Chris Hani Baragwanath Academic Hospital ( Site 0262)
state: Gauteng
city: Cape Town
country: South Africa
facility: Tygerberg Hospital ( Site 0261)
state: Western Cape
city: Santiago de Compostela
country: Spain
facility: Hospital Clinico Universitario de Santiago ( Site 0241)
state: La Coruna
city: Madrid
country: Spain
facility: Hospital Universitario La Paz ( Site 0242)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.