Clesrovimab (MK-1654) in Infants and Children at Increased Risk for Severe Respiratory Syncytial Virus (RSV) Disease (MK-1654-007)

NCT04938830
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Phase
Phase 3
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Recruitment status
Completed
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Participants
1,003
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Lead sponsor
Merck Sharp & Dohme LLC
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Start date
2021-11-30
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Number of sites
146
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Summary
This study aims to evaluate the safety and tolerability of clesrovimab compared to palivizumab as assessed by the proportion of participants experiencing adverse events (AEs).
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Acronym
SMART
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Short title
Clesrovimab (MK-1654) in Infants and Children at Increased Risk for Severe Respiratory Syncytial Virus (RSV) Disease (MK-1654-007)
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Official title
A Phase 3, Multicenter, Randomized, Partially Blinded, Palivizumab- Controlled Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of MK-1654 in Infants and Children at Increased Risk for Severe RSV Disease
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Control arm
Active comparator
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Registry reports results
Yes
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Listing at source
Listed
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Recruitment status
Completed
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Phase
Phase 3
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Study type
Interventional
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Completion date
2025-08-01
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First posted
2021-06-24
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Registry last updated
2026-05-08
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Primary completion date
2025-04-28
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Start date
2021-11-30
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Actual participants
1,003
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Participants
1,003
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Participant count basis
Actual
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Protocol amendments
4
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Number of sites
146
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Data monitoring committee
Yes
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Registry sponsor category
Industry
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Lead sponsor
Merck Sharp & Dohme LLC
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Source registry
ClinicalTrials.gov
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Registry ID
NCT04938830
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ClinicalTrials.gov ID
NCT04938830
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Registry record
Open registry record
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Allocation
Randomised
Model
Parallel groups
Purpose
Prevention
Masking
Triple masking
Masking description
Randomization occurs on Day 1. Part 1 of this study uses a double-blinding technique until Day 60. Part 2 is unblinded conducted as open-label.
Masked roles
Participants, Care providers, Investigators
Sources for study design
clinicaltrials.gov

  1. Number of Participants With Solicited Injection-site Adverse Events (AEs) in RSV Season 1

    Timeframe: Up to 5 days after each dose in RSV Season 1 (Up to ~33 days)

    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 included erythema, pain, and swelling. The number of participants with solicited injection-site AEs in RSV Season 1 is reported.

  2. Number of Participants With Solicited Daily Body Temperatures With Fever in RSV Season 1

    Timeframe: Up to 5 days after each dose in RSV Season 1 (Up to ~33 days)

    Fever was defined as maximum rectal temperature ≥102.2 °F (39.0 °C) or maximum axillary temperature ≥101.7 °F. The number of participants with solicited daily body temperature of fever in RSV Season 1 is reported.

  3. Number of Participants With Solicited Systemic AEs in RSV Season 1

    Timeframe: Up to 5 days after each dose in RSV Season 1 (Up to ~33 days)

    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 included decreased appetite, irritability, and somnolence. The number of participants with solicited systemic AEs in RSV Season 1 is reported.

  4. Number of Participants With Anaphylaxis/Hypersensitivity AEs of Special Interest (AESI) in RSV Season 1

    Timeframe: Up to 42 days in RSV Season 1

    An AE was 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. The number of participants with anaphylaxis/hypersensitivity AESI in RSV Season 1 is reported.

  5. Number of Participants With Rash AESI in RSV Season 1

    Timeframe: Up to 42 days in RSV Season 1

    An AE was 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. Rash AESI included urticaria and drug eruption. The number of participants with rash AESI in RSV Season 1 is reported.

  6. Number of Participants With Nonserious AEs in RSV Season 1

    Timeframe: Up to 42 days in RSV Season 1

    An AE was 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. The number of participants with nonserious AEs in RSV Season 1 is reported.

  7. Number of Participants With Serious AEs (SAEs) Through the Duration of Participation in RSV Season 1

    Timeframe: Up to 365 days in RSV Season 1

    An SAE is any untoward medical occurrence in a clinical study participant that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is another important medical event. The number of participants with SAEs in RSV Season 1 is reported.

  1. Number of Cases of RSV-associated Medically Attended Lower Respiratory Infection (MALRI) in RSV Season 1

    Timeframe: Up to 150 days in RSV Season 1

    Outpatient and inpatient MALRI was defined as the presence of the following in a clinical setting: 1) cough or difficulty breathing; AND 2) 1 or more of wheezing, chest wall in-drawing/retraction, rales/crackles, hypoxemia, tachypnea, or dehydration due to respiratory symptoms; AND 3) RSV-positive reverse transcriptase polymerase chain reaction (RT-PCR) nasopharyngeal (NP) sample. The number of cases of outpatient and inpatient RSV-associated MALRI were reported together for RSV season 1. For each participant, only the first occurrence of the case is counted for the analysis.

  2. Number of Cases of RSV-associated Hospitalization in RSV Season 1

    Timeframe: Up to 150 days in RSV Season 1

    RSV-associated hospitalization is defined as a hospital admission for respiratory illness and RSV-positive RT-PCR NP sample. The number of cases of RSV-associated hospitalization in RSV Season 1 is reported. For each participant, only the first occurrence of the case is counted for the analysis.

  3. Number of Participants With Solicited Injection-site AEs in RSV Season 2

    Timeframe: Up to 5 days postdose in RSV Season 2 (Up to ~400 days)

    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 included erythema, pain, and swelling. The number of participants with solicited injection-site AEs in RSV Season 2 is reported.

  4. Number of Participants With Solicited Daily Body Temperature With Fever in RSV Season 2

    Timeframe: Up to 5 days postdose in RSV Season 2 (Up to ~400 days)

    Fever was defined as maximum rectal temperature ≥102.2 °F (39.0 °C) or maximum axillary temperature ≥101.7 °F. The number of participants with solicited daily body temperature of fever in RSV Season 2 is reported.

  5. Number of Participants With Solicited Systemic AEs in RSV Season 2

    Timeframe: Up to 5 days postdose in RSV Season 2 (Up to ~400 days)

    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 included decreased appetite, irritability, and somnolence. The number of participants with solicited systemic AEs in RSV Season 2 is reported.

  6. Number of Participants With Anaphylaxis/Hypersensitivity AESI in RSV Season 2

    Timeframe: Up to 42 days postdose in RSV Season 2 (Up to ~440 days)

    An AE was 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. The number of participants with anaphylaxis/hypersensitivity AESI in RSV Season 2 is reported.

  7. Number of Participants With Rash AESI in RSV Season 2

    Timeframe: Up to 42 days postdose in RSV Season 2 (Up to ~440 days)

    An AE was 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. Rash AESI included urticaria and drug eruption. The number of participants with rash AESI in RSV Season 2 is reported.

  8. Number of Participants With Nonserious AEs in RSV Season 2

    Timeframe: Up to 42 days postdose in RSV Season 2 (Up to ~440 days)

    An AE was 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. The number of participants with nonserious AEs in RSV Season 2 is reported.

  9. Number of Participants With SAEs in RSV Season 2

    Timeframe: Up 180 days postdose in RSV Season 2 (Up to ~575 days)

    An SAE is any untoward medical occurrence in a clinical study participant that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is another important medical event. The number of participants with SAEs in RSV Season 2 is reported.

  10. Concentration of Clesrovimab in RSV Season 1

    Timeframe: At Day 7, Day 150, and Day 240 in RSV Season 1

    Blood samples were collected to determine the serum concentration of clesrovimab at Days 7, 150, and 240 in RSV Season 1.

  11. Concentration of Clesrovimab in RSV Season 2

    Timeframe: At Day 7 and Day 150 postdose in RSV Season 2

    Blood samples were collected to determine the serum concentration of clesrovimab at Days 7 and 150 in RSV Season 2. RSV Season 2 began 246-393 days after RSV Season 1 dose 1.

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Children
Maximum age
1 Year
Healthy volunteers
No

  • Participants at increased risk for severe RSV infection recommended to receive palivizumab in accordance with national or local guidelines or professional society recommendations and meet defined criteria for the Early or Moderate Pre-term Group or the chronic lung disease (CLD)/congenital heart disease (CHD) Group.
  • Is available to complete the follow-up period.

Additional inclusion criteria for participation in RSV Season 2:

  • RSV Season 2 participants enrolled in the CLD/CHD Group in RSV Season 1. Participants with CHD must also have the following:

    • Hemodynamically significant CHD at the beginning of RSV Season 2, or
    • If the participant has had surgically repaired hemodynamically significant CHD that did not include extracorporeal membrane oxygenation (ECMO) or cardiopulmonary bypass: 1) continues to require medications to manage CHD, or 2) any additional medical intervention related to their CHD.

  • RSV Season 2 participants enrolled in the Early or Moderate Pre-term Group in RSV Season 1, with the following:

    • Neuromuscular disease or congenital pulmonary anomaly that impairs the ability to clear secretions from the upper airway because of ineffective cough
    • Down Syndrome (trisomy of chromosome 21)
    • Cystic fibrosis with nutritional compromise
    • Native Americans and Alaskan Indians or other indigenous populations at high risk for severe RSV disease

  • Requires mechanical ventilation at time of enrollment.
  • Has a life expectancy <6 months.
  • Has known hepatic or renal dysfunction, or chronic seizure disorder.
  • Is hospitalized at the time of randomization unless discharge is expected within 7 days after randomization.
  • Has severe immunodeficiency or is severely immunocompromised.
  • Has known hypersensitivity to any component of clesrovimab or palivizumab.

Additional exclusion criteria for participation in RSV Season 2:

  • Had 1) ECMO or 2) surgical intervention during the RSV season for CHD and required cardiopulmonary bypass during the procedure in RSV Season 1.
Sources for eligibility
clinicaltrials.gov

  • Miller Children's & Women's Hospital Long Beach ( Site 0001)Long Beach, United States
  • Children's Hospital of Orange County ( Site 0047)Orange, United States
  • Children's Hospital Colorado ( Site 0011)Aurora, United States
  • Children's National Medical Center ( Site 0020)Washington D.C., United States
  • Orlando Health - Arnold Palmer Hospital-Orlando Health-Arnold Palmer Hospital Pulmonary and Sleep M ( Site 0022)Orlando, United States
  • Nemours Children's Health, Lake Nona Medical City ( Site 0032)Orlando, United States
  • University of South Florida-Department of Pediatrics ( Site 0045)Tampa, United States
  • Morehouse School Of Medicine ( Site 0049)Atlanta, United States
  • Clinical Research Prime ( Site 0046)Idaho Falls, United States
  • University of Kentucky HealthCare - Turfland ( Site 0044)Lexington, United States
  • Our Lady of the Lake Children's Hospital ( Site 0031)Baton Rouge, United States
  • Tulane University School of Medicine ( Site 0010)New Orleans, United States
  • M Health Fairview University of Minnesota Masonic Children's Hospital, West Bank-Peds Research ( Site 0037)Minneapolis, United States
  • Rutgers University-Pediatric Clinical Research Center ( Site 0007)New Brunswick, United States
  • NYU Langone Hospital - Long Island-Pediatrics ( Site 0028)Mineola, United States
  • University of Rochester Medical Center ( Site 0017)Rochester, United States
  • The University of North Carolina at Chapel Hill ( Site 0035)Chapel Hill, United States
  • Duke University ( Site 0021)Durham, United States
  • Dayton Children's Hospital ( Site 0053)Dayton, United States
  • Tribe Clinical Research, LLC ( Site 0002)Greenville, United States
  • Driscoll Children's Hospital ( Site 0025)Corpus Christi, United States
  • DHR Health Institute for Research and Development ( Site 0029)Edinburg, United States
  • Christus Children's-Clinical Research Center ( Site 0038)San Antonio, United States
  • University Hospital-Pediatrics ( Site 0019)San Antonio, United States
  • Road Runner Research, Ltd ( Site 0052)San Antonio, United States

And 121 more, listed on the interactive page.

Sources for sites
clinicaltrials.gov

  • MK-1654-007
  • U1111-1278-0093
  • jRCT2031210664
  • 2022-500752-39-00
  • 2020-005996-11
Sources for references
clinicaltrials.gov

Related records

Drugs (2)

Lead sponsors (1)

Conditions (1)