RSV Infection
Conditions
Brief 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).
Interventions
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
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.
Eligibility
Sex/Gender
ALL
Age
No minimum to 1 Years
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Solicited Injection-site Adverse Events (AEs) in RSV Season 1 | 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. |
| Number of Participants With Solicited Daily Body Temperatures With Fever in RSV Season 1 | 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. |
| Number of Participants With Solicited Systemic AEs in RSV Season 1 | 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. |
| Number of Participants With Anaphylaxis/Hypersensitivity AEs of Special Interest (AESI) in RSV Season 1 | 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. |
| Number of Participants With Rash AESI in RSV Season 1 | 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. |
| Number of Participants With Nonserious AEs in RSV Season 1 | 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. |
| Number of Participants With Serious AEs (SAEs) Through the Duration of Participation in RSV Season 1 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Cases of RSV-associated Medically Attended Lower Respiratory Infection (MALRI) in RSV Season 1 | 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. |
| Number of Cases of RSV-associated Hospitalization in RSV Season 1 | 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. |
| Number of Participants With Solicited Injection-site AEs in RSV Season 2 | 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. |
| Number of Participants With Solicited Daily Body Temperature With Fever in RSV Season 2 | 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. |
| Number of Participants With Solicited Systemic AEs in RSV Season 2 | 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. |
| Number of Participants With Anaphylaxis/Hypersensitivity AESI in RSV Season 2 | 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. |
| Number of Participants With Rash AESI in RSV Season 2 | 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. |
| Number of Participants With Nonserious AEs in RSV Season 2 | 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. |
| Number of Participants With SAEs in RSV Season 2 | 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. |
| Concentration of Clesrovimab in RSV Season 1 | 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. |
| Concentration of Clesrovimab in RSV Season 2 | 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. |
Countries
Australia, Canada, Chile, Colombia, Czechia, Finland, France, Germany, Greece, Hong Kong, Hungary, Italy, Japan, Malaysia, Mexico, New Zealand, Norway, Peru, Puerto Rico, Singapore, South Africa, Spain, Taiwan, Thailand, Turkey (Türkiye), United Kingdom, United States
Contacts
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Participant flow
Pre-assignment details
Part 1 (blinded dose) is Day 1 through Day 60 of respiratory syncytial virus (RSV) Season 1. Part 2 (unblinded dose) began on Day 60. A subset of participants from the RSV Season 1 entered RSV Season 2.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 0.3 Years STANDARD_DEVIATION 0.2 |
| Age, Customized Infants and toddlers (28 days-23 months) | 447 Participants |
| Age, Customized Newborns (0-27 days) | 55 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 157 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 336 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 8 Participants |
| Participant Condition CHD | 52 Participants |
| Participant Condition CLD | 139 Participants |
| Participant Condition Neither CLD nor CHD <29 weeks gestational age | 80 Participants |
| Participant Condition Neither CLD nor CHD ≥29 weeks gestational age | 268 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 9 Participants |
| Race (NIH/OMB) Asian | 176 Participants |
| Race (NIH/OMB) Black or African American | 166 Participants |
| Race (NIH/OMB) More than one race | 129 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 5 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 510 Participants |
| Region at Randomization Northern Hemisphere | 708 Participants |
| Region at Randomization Southern Hemisphere | 295 Participants |
| Sex: Female, Male Female | 251 Participants |
| Sex: Female, Male Male | 255 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 8 / 502 | 4 / 501 | 1 / 138 | 1 / 138 |
| other Total, other adverse events | 290 / 497 | 282 / 499 | 69 / 138 | 69 / 138 |
| serious Total, serious adverse events | 122 / 497 | 137 / 499 | 25 / 138 | 26 / 138 |
Outcome results
None listed