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NCT03524118

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

Completed Phase 1, PHASE2 Results posted Last updated 14 January 2025
What this trial tests

Phase 1, PHASE2 trial testing Clesrovimab in Respiratory Tract Infection in 183 participants. Completed in 14 September 2022.

Timeline
20 September 2018
Primary endpoint
14 September 2022
14 September 2022

Quick facts

Lead sponsorMerck Sharp & Dohme LLC
PhasePhase 1, PHASE2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designsequential
Maskingtriple
Primary purposeprevention
Enrollment183
Start date20 September 2018
Primary completion14 September 2022
Estimated completion14 September 2022
Sites34 locations across Colombia, South Africa, Chile, South Korea, United States, Spain

Drugs / interventions tested

Conditions studied

Sponsor

Merck Sharp & Dohme LLC — full company profile →

Who can join

Adults 2 Weeks to 8 Months, any sex, with Respiratory Tract Infection or Respiratory Syncytial Virus. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants Who Experienced At Least One Solicited Injection Site Adverse Event (AE) Primary · Up to Day 5

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.

with solicited injection site adverse events
GroupValue95% CI
Panel A: Preterm Clesrovimab 20mg3
Panel B: Pre-term Clesrovimab 50mg3
Panel C: Pre-term Clesrovimab 75mg3
Panel D1 and D2: Pre-term Clesrovimab 100mg2
Panel E1 and E2: Full-term Clesrovimab 100mg2
Placebo2
without solicited injection site adverse events
GroupValue95% CI
Panel A: Preterm Clesrovimab 20mg3
Panel B: Pre-term Clesrovimab 50mg30
Panel C: Pre-term Clesrovimab 75mg37
Panel D1 and D2: Pre-term Clesrovimab 100mg30
Panel E1 and E2: Full-term Clesrovimab 100mg30
Placebo36
Percentage of Participants Who Experienced At Least One Solicited Systemic Adverse Event (AE) Primary · Up to Day 5

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.

with solicited systemic adverse events
GroupValue95% CI
Panel A: Preterm Clesrovimab 20mg2
Panel B: Pre-term Clesrovimab 50mg8
Panel C: Pre-term Clesrovimab 75mg9
Panel D1 and D2: Pre-term Clesrovimab 100mg2
Panel E1 and E2: Full-term Clesrovimab 100mg3
Placebo9
without solicited systemic adverse events
GroupValue95% CI
Panel A: Preterm Clesrovimab 20mg4
Panel B: Pre-term Clesrovimab 50mg25
Panel C: Pre-term Clesrovimab 75mg31
Panel D1 and D2: Pre-term Clesrovimab 100mg30
Panel E1 and E2: Full-term Clesrovimab 100mg29
Placebo29
Percentage of Participants Who Experienced At Least One Serious Adverse Event (SAE) Primary · Up to Day 545

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.

with serious adverse events (SAE)
GroupValue95% CI
Panel A: Preterm Clesrovimab 20mg1
Panel B: Pre-term Clesrovimab 50mg4
Panel C: Pre-term Clesrovimab 75mg1
Panel D1 and D2: Pre-term Clesrovimab 100mg3
Panel E1 and E2: Full-term Clesrovimab 100mg6
Placebo6
without SAE
GroupValue95% CI
Panel A: Preterm Clesrovimab 20mg5
Panel B: Pre-term Clesrovimab 50mg29
Panel C: Pre-term Clesrovimab 75mg39
Panel D1 and D2: Pre-term Clesrovimab 100mg29
Panel E1 and E2: Full-term Clesrovimab 100mg26
Placebo32
Area Under the Serum-Concentration Time Curve From Zero to Infinity (AUC0-∞) Secondary · At designated time points (up to 1 year post-dose)

AUC0-∞ is a measure of the extrapolated mean concentration in serum from dosing to infinity.

GroupValue95% CI
Panel A: Preterm Clesrovimab 20mg1560± 43.5
Panel B: Pre-term Clesrovimab 50mg3520± 22.8
Panel C: Pre-term Clesrovimab 75mg5510± 22.4
Panel D1 and D2: Pre-term Clesrovimab 100mg6790± 25.4
Panel E1 and E2: Full-term Clesrovimab 100mg5690± 15.9
Maximum Serum Concentration (Cmax) of Clesrovimab Secondary · At designated time points (up to 1 year post-dose)

Cmax is the highest observed serum drug concentration.

GroupValue95% CI
Panel A: Preterm Clesrovimab 20mg26.3± 19.3
Panel B: Pre-term Clesrovimab 50mg61.7± 21.8
Panel C: Pre-term Clesrovimab 75mg94.5± 20.5
Panel D1 and D2: Pre-term Clesrovimab 100mg117± 23.5
Panel E1 and E2: Full-term Clesrovimab 100mg99.9± 13.7
Time to Maximum Serum Concentration (Tmax) of Clesrovimab Secondary · At designated time points (up to 1 year post-dose)

Tmax is the time taken to reach the maximum observed plasma (Cmax) concentration of Clesrovimab.

GroupValue95% CI
Panel A: Preterm Clesrovimab 20mg4.03.8 – 4.60
Panel B: Pre-term Clesrovimab 50mg4.203.70 – 5.30
Panel C: Pre-term Clesrovimab 75mg4.203.00 – 5.80
Panel D1 and D2: Pre-term Clesrovimab 100mg4.103.70 – 6.00
Panel E1 and E2: Full-term Clesrovimab 100mg4.103.70 – 4.90
Apparent Terminal Half-life (t1/2) of Clesrovimab Secondary · At designated time points (up to 1 year post-dose)

t1/2 is the time required for 50% of drug to be cleared from serum.

GroupValue95% CI
Panel A: Preterm Clesrovimab 20mg48.8± 34.6
Panel B: Pre-term Clesrovimab 50mg44.6± 10.9
Panel C: Pre-term Clesrovimab 75mg46.1± 15.1
Panel D1 and D2: Pre-term Clesrovimab 100mg45.2± 13.7
Panel E1 and E2: Full-term Clesrovimab 100mg43.0± 9.72
Serum Concentration of Clesrovimab on Day 7 (C7days) Secondary · Day 7

Serum concentration of clesrovimab was measured on Day 7.

GroupValue95% CI
Panel A: Preterm Clesrovimab 20mg24.4± 20.4
Panel B: Pre-term Clesrovimab 50mg57.8± 21.6
Panel C: Pre-term Clesrovimab 75mg88.1± 20.4
Panel D1 and D2: Pre-term Clesrovimab 100mg109± 23.0
Panel E1 and E2: Full-term Clesrovimab 100mg92.8± 13.3
Serum Concentration of Clesrovimab on Day 14 (C14days) Secondary · Day 14

Serum concentration of clesrovimab was measured on Day 14.

GroupValue95% CI
Panel A: Preterm Clesrovimab 20mg19.4± 22.1
Panel B: Pre-term Clesrovimab 50mg46.8± 20.6
Panel C: Pre-term Clesrovimab 75mg71.1± 19.7
Panel D1 and D2: Pre-term Clesrovimab 100mg88.6± 21.8
Panel E1 and E2: Full-term Clesrovimab 100mg75.4± 12.9
Serum Concentration of Clesrovimab on Day 90 (C90days) Secondary · Day 90

Serum concentration of clesrovimab was measured on Day 90.

GroupValue95% CI
Panel A: Preterm Clesrovimab 20mg5.60± 49.5
Panel B: Pre-term Clesrovimab 50mg13.0± 25.4
Panel C: Pre-term Clesrovimab 75mg20.4± 25.8
Panel D1 and D2: Pre-term Clesrovimab 100mg25.2± 28.6
Panel E1 and E2: Full-term Clesrovimab 100mg21.1± 18.8
Serum Concentration of Clesrovimab on Day 150 (C150days) Secondary · Day 150

Serum concentration of clesrovimab was measured on Day 150.

GroupValue95% CI
Panel A: Preterm Clesrovimab 20mg2.24± 80.6
Panel B: Pre-term Clesrovimab 50mg4.98± 34.2
Panel C: Pre-term Clesrovimab 75mg8.05± 37.7
Panel D1 and D2: Pre-term Clesrovimab 100mg9.70± 40.2
Panel E1 and E2: Full-term Clesrovimab 100mg7.96± 26.7
Serum Concentration of Clesrovimab on Day 365 (C365days) Secondary · Day 365

Serum concentration of clesrovimab was measured on Day 365.

GroupValue95% CI
Panel A: Preterm Clesrovimab 20mg0.0953± 362
Panel B: Pre-term Clesrovimab 50mg0.177± 79.4
Panel C: Pre-term Clesrovimab 75mg0.313± 107
Panel D1 and D2: Pre-term Clesrovimab 100mg0.355± 104
Panel E1 and E2: Full-term Clesrovimab 100mg0.248± 63.1

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to Day 545. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

MK-1654 20 mg in Pre-term Infants
Serious: 1/6 (17%)
Deaths: 0/8
MK-1654 50 mg in Pre-term Infants
Serious: 4/33 (12%)
Deaths: 0/31
MK-1654 75 mg in Pre-term Infants
Serious: 1/40 (3%)
Deaths: 0/41
MK-1654 100 mg Pre-Term Infants
Serious: 3/32 (9%)
Deaths: 0/32
MK-1654 100 mg Full-Term Infants
Serious: 6/32 (19%)
Deaths: 0/33
Placebo
Serious: 6/38 (16%)
Deaths: 0/38

Serious adverse events (15 terms)

ReactionSystemMK-1654 20 mg in Pre-term …MK-1654 50 mg in Pre-term …MK-1654 75 mg in Pre-term …MK-1654 100 mg Pre-Term In…MK-1654 100 mg Full-Term I…Placebo
Respiratory syncytial virus bronchiolitisInfections and infestations
BronchiolitisInfections and infestations
PneumoniaInfections and infestations
Gastrooesophageal reflux diseaseGastrointestinal disorders
Biliary cystHepatobiliary disorders
COVID-19Infections and infestations
CellulitisInfections and infestations
Croup infectiousInfections and infestations
GastroenteritisInfections and infestations
Respiratory syncytial virus infectionInfections and infestations
Rhinovirus infectionInfections and infestations
Toxicity to various agentsInjury, poisoning and procedural complications
Wound dehiscenceInjury, poisoning and procedural complications
DehydrationMetabolism and nutrition disorders
Irregular breathingRespiratory, thoracic and mediastinal disorders
Other adverse events (38 terms — click to expand)

ReactionSystemMK-1654 20 mg in Pre-term …MK-1654 50 mg in Pre-term …MK-1654 75 mg in Pre-term …MK-1654 100 mg Pre-Term In…MK-1654 100 mg Full-Term I…Placebo
Upper respiratory tract infectionInfections and infestations
NasopharyngitisInfections and infestations
IrritabilityPsychiatric disorders
Nasal congestionRespiratory, thoracic and mediastinal disorders
BronchiolitisInfections and infestations
GastroenteritisInfections and infestations
DiarrhoeaGastrointestinal disorders
Viral upper respiratory tract infectionInfections and infestations
SomnolenceNervous system disorders
RhinorrhoeaRespiratory, thoracic and mediastinal disorders
Rash papularSkin and subcutaneous tissue disorders
FlatulenceGastrointestinal disorders
TeethingGastrointestinal disorders
BronchitisInfections and infestations
COVID-19Infections and infestations
Croup infectiousInfections and infestations
Otitis mediaInfections and infestations
CoughRespiratory, thoracic and mediastinal disorders
ConstipationGastrointestinal disorders
Injection site erythemaGeneral disorders
Injection site painGeneral disorders
Injection site swellingGeneral disorders
PyrexiaGeneral disorders
ConjunctivitisInfections and infestations
Ear infectionInfections and infestations
Lower respiratory tract infectionInfections and infestations
Otitis media acuteInfections and infestations
Respiratory tract infectionInfections and infestations
RhinitisInfections and infestations
Viral pharyngitisInfections and infestations
Accidental overdoseInjury, poisoning and procedural complications
Dermatitis diaperSkin and subcutaneous tissue disorders
MiliariaSkin and subcutaneous tissue disorders
RashSkin and subcutaneous tissue disorders
Rash maculo-papularSkin and subcutaneous tissue disorders
ContusionInjury, poisoning and procedural complications
Decreased appetiteMetabolism and nutrition disorders
PruritusSkin and subcutaneous tissue disorders

Most-reported serious reactions: Respiratory syncytial virus bronchiolitis, Bronchiolitis, Pneumonia, Gastrooesophageal reflux disease, Biliary cyst, COVID-19, Cellulitis, Croup infectious.

Data from ClinicalTrials.gov NCT03524118 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Respiratory syncytial virus prevention within reach: the vaccine and monoclonal antibody landscape.
    Mazur NI, Terstappen J, Baral R, Bardají A, et al · · 2023 · cited 294× · PMID 35952703 · DOI 10.1016/s1473-3099(22)00291-2
  2. The Future of Respiratory Syncytial Virus Disease Prevention and Treatment.
    Domachowske JB, Anderson EJ, Goldstein M. · · 2021 · cited 90× · PMID 33656652 · DOI 10.1007/s40121-020-00383-6
  3. Current State and Challenges in Developing Respiratory Syncytial Virus Vaccines.
    Biagi C, Dondi A, Scarpini S, Rocca A, et al · · 2020 · cited 45× · PMID 33187337 · DOI 10.3390/vaccines8040672
  4. Priorities for developing respiratory syncytial virus vaccines in different target populations.
    Drysdale SB, Barr RS, Rollier CS, Green CA, et al · · 2020 · cited 38× · PMID 32188721 · DOI 10.1126/scitranslmed.aax2466
  5. Prevention of Pediatric Respiratory Syncytial Virus Lower Respiratory Tract Illness: Perspectives for the Next Decade.
    Aranda SS, Polack FP. · · 2019 · cited 37× · PMID 31134078 · DOI 10.3389/fimmu.2019.01006
  6. A Phase 1b/2a Trial of a Half-life Extended Respiratory Syncytial Virus Neutralizing Antibody, Clesrovimab, in Healthy Preterm and Full-term Infants.
    Madhi SA, Simões EAF, Acevedo A, Novoa Pizarro JM, et al · · 2025 · cited 28× · PMID 39601265 · DOI 10.1093/infdis/jiae581
  7. The long road to protect infants against severe RSV lower respiratory tract illness.
    Jares Baglivo S, Polack FP. · · 2019 · cited 26× · PMID 31105933 · DOI 10.12688/f1000research.18749.1
  8. Review and Update of Active and Passive Immunization Against Respiratory Syncytial Virus.
    Verwey C, Madhi SA. · · 2023 · cited 24× · PMID 37097594 · DOI 10.1007/s40259-023-00596-4

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03524118.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing