Respiratory Syncytial Virus Infection
Conditions
Brief summary
The primary objectives of this phase 2b/3 double-blind, randomized, placebo-controlled study are to evaluate the efficacy and safety of clesrovimab in healthy pre-term and full-term infants. It is hypothesized that clesrovimab will reduce the incidence of respiratory syncytial virus (RSV)-associated medically attended lower respiratory infection (MALRI) from Days 1 through 150 postdose compared to placebo.
Interventions
BIOLOGICALClesrovimab
Clesrovimab solution
DRUGPlacebo
Placebo (0.9% sodium chloride \[NaCL\]) solution
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
No minimum to 1 Years
Healthy volunteers
Yes
Inclusion criteria
Key Inclusion Criteria: * Is a healthy male or female who is an early or moderate pre-term infant (≥29 to 34 weeks and 6 days gestational age) or a late pre-term or full-term infant (≥35 weeks gestational age) * For the phase 2b cohort only: Has a chronological age \>2 weeks of age up to 1 year and is entering their first respiratory syncytial virus (RSV) season at the time of obtaining documented informed consent. * For the phase 3 cohort only: Has a chronological age from birth up to 1 year and is entering their first RSV season at the time of obtaining documented informed consent. * For participants in South Korea only: Weighs ≥2 kg Key
Exclusion criteria
* Is recommended to receive palivizumab per local guidelines or professional society recommendations. * Has known hypersensitivity to any component of clesrovimab * Has a bleeding disorder contraindicating IM administration * Has had a recent illness with rectal temperature ≥100.5°F (≥38.1°C) or axillary temperature ≥100.0°F (≥37.8°C) within 72 hours predose * Has received any vaccine or monoclonal antibody 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 before first dose administration or while participating in this study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| RSV Season 1: Number of Participants With Respiratory Syncytial Virus (RSV)-Associated Medically Attended Lower Respiratory Infection (MALRI) | From Day 1 (postdose) to Day 150 | 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 sample. Per protocol, the participants with outpatient and inpatient RSV-associated MALRI were reported together for RSV season 1 participants. |
| RSV Season 1: Percentage of Participants With Solicited Injection-Site Adverse Events (AEs) | From Day 1 (postdose) to Day 5 | 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. Solicited injection-site AEs included redness/erythema, swelling, and pain/tenderness. Per protocol, the percentage of RSV season 1 participants with solicited injection-site AEs were reported. |
| RSV Season 1: Percentage of Participants With Fever | From Day 1 (postdose) to Day 5 | Fever was defined as rectal temperature ≥102.2°F (≥39.0°C) or axillary temperature ≥101.7°F (≥38.7°C). Per protocol, the percentage of RSV season 1 participants with fever were reported. |
| RSV Season 1: Percentage of Participants With Solicited Systemic AEs | From Day 1 (postdose) to Day 5 | 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. Solicited systemic AEs included irritability, somnolence/drowsiness, and appetite lost. Per protocol, the percentage of RSV season 1 participants with solicited systemic AEs were reported. |
| RSV Season 1: Percentage of Participants With Anaphylaxis/Hypersensitivity AE of Special Interest (AESI) | From Day 1 (postdose) to Day 42 | 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. Anaphylaxis/Hypersensitivity AESI included anaphylaxis, angioedema, bronchospasm, drug hypersensitivity, dyspnea, hypersensitivity, dysphonia, and wheezing. Per protocol, the percentage of RSV season 1 participants with anaphylaxis/hypersensitivity AESI were reported. |
| RSV Season 1: Percentage of Participants With Rash AESI | From Day 1 (postdose) to Day 42 | 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 acute generalized exanthematous pustulosis, drug eruption, drug reaction with eosinophilia and systemic symptoms, erythema multiforme, generalized rash of exfoliative nature, Stevens-Johnson syndrome, toxic epidermal necrolysis, and urticaria. Per protocol, the percentage of RSV season 1 participants with rash AESI were reported. |
| RSV Season 1: Percentage of Participants With ≥1 Nonserious AE | From Day 1 (postdose) to Day 42 | 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. Per protocol, the percentage of RSV season 1 participants with ≥1 nonserious AE were reported. |
| Percentage of Participants With Serious Adverse Events (SAEs) | RSV Season 1: Day 1 to Day 365, RSV Season 2: Day 366 to Day 515 | An SAE was any untoward medical occurrence that results in death; is life-threatening; required inpatient hospitalization/prolongs existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or other important medical event. Per protocol, the percentage of participants in RSV season 1 and RSV season 2 with SAEs were reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| RSV Season 1: Number of Participants With RSV-Associated Hospitalization | From Day 1 (postdose) to Day 150 | RSV-associated hospitalization is defined as a hospital admission for respiratory illness and RSV-positive RT-PCR nasopharyngeal sample. Per protocol, the number of participants with RSV-associated hospitalization were reported for RSV season 1. |
| RSV Season 1: Number of Participants With RSV-Associated MALRI | From Day 1 (postdose) to Day 180 | 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 RT-PCR nasopharyngeal sample. Per protocol, participants with outpatient and inpatient RSV-associated MALRI were reported together for RSV season 1 participants. |
Countries
Argentina, Belgium, Canada, Chile, China, Colombia, Denmark, Finland, France, Israel, Italy, Japan, Malaysia, Mexico, Peru, Philippines, Poland, Romania, South Africa, South Korea, Thailand, Turkey (Türkiye), United Kingdom, United States
Contacts
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Participant flow
Pre-assignment details
Per protocol, participants received one dose of study treatment on Day 1 during RSV Season 1. Participants did not receive study treatment during RSV Season 2. Study disposition data were not collected separately for RSV season 1 and RSV Season 2.
Participants by arm
| Arm | Count |
|---|---|
| Clesrovimab 105 mg Participants received a single intramuscular (IM) administration of clesrovimab 105 mg on Day 1. An eligible subset of participants from RSV Season 1 entered RSV season 2. | 2,421 |
| Placebo Participants received a single IM administration of placebo on Day 1. An eligible subset of participants from RSV Season 1 entered RSV season 2. | 1,211 |
| Total | 3,632 |
Baseline characteristics
| Characteristic | Placebo | Clesrovimab 105 mg | Total |
|---|---|---|---|
| Age at randomization <6 months | 964 Participants | 1927 Participants | 2891 Participants |
| Age at randomization ≥6 months | 247 Participants | 494 Participants | 741 Participants |
| Age, Continuous | 0.3 Years STANDARD_DEVIATION 0.2 | 0.3 Years STANDARD_DEVIATION 0.2 | 0.3 Years STANDARD_DEVIATION 0.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 335 Participants | 685 Participants | 1020 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 841 Participants | 1667 Participants | 2508 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 35 Participants | 69 Participants | 104 Participants |
| Gestational Age Early and Moderate Preterm Infant (≥29 to <35 weeks) | 213 Participants | 425 Participants | 638 Participants |
| Gestational Age Late Preterm and Full-term Infant (≥35 weeks) | 998 Participants | 1996 Participants | 2994 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 18 Participants | 50 Participants | 68 Participants |
| Race (NIH/OMB) Asian | 321 Participants | 646 Participants | 967 Participants |
| Race (NIH/OMB) Black or African American | 173 Participants | 326 Participants | 499 Participants |
| Race (NIH/OMB) More than one race | 139 Participants | 304 Participants | 443 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 6 Participants | 9 Participants | 15 Participants |
| Race (NIH/OMB) White | 553 Participants | 1085 Participants | 1638 Participants |
| Region at randomization Northern Hemisphere | 818 Participants | 1657 Participants | 2475 Participants |
| Region at randomization Southern Hemisphere | 393 Participants | 764 Participants | 1157 Participants |
| Sex: Female, Male Female | 593 Participants | 1187 Participants | 1780 Participants |
| Sex: Female, Male Male | 618 Participants | 1234 Participants | 1852 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 | 7 / 2,421 | 3 / 1,211 | 0 / 1,017 | 0 / 501 |
| other Total, other adverse events | 1,432 / 2,409 | 724 / 1,202 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 282 / 2,409 | 151 / 1,202 | 32 / 1,017 | 20 / 501 |
Outcome results
Primary
Percentage of Participants With Serious Adverse Events (SAEs)
An SAE was any untoward medical occurrence that results in death; is life-threatening; required inpatient hospitalization/prolongs existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or other important medical event. Per protocol, the percentage of participants in RSV season 1 and RSV season 2 with SAEs were reported.
Time frame: RSV Season 1: Day 1 to Day 365, RSV Season 2: Day 366 to Day 515
Population: Safety analysis population which included all randomized participants who received a dose of protocol specified study treatment. For safety analysis population, participants with protocol deviation were excluded. Per protocol, a subset of participants from RSV season 1 entered RSV season 2 and SAEs were collected separately for RSV season 1 and RSV Season 2.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RSV Season 1: Clesrovimab 105 mg | Percentage of Participants With Serious Adverse Events (SAEs) | 11.7 Percentage of participants |
| RSV Season 1: Placebo | Percentage of Participants With Serious Adverse Events (SAEs) | 12.6 Percentage of participants |
| RSV Season 2: Clesrovimab 105 mg | Percentage of Participants With Serious Adverse Events (SAEs) | 3.1 Percentage of participants |
| RSV Season 2: Placebo | Percentage of Participants With Serious Adverse Events (SAEs) | 4.0 Percentage of participants |
Primary
RSV Season 1: Number of Participants With Respiratory Syncytial Virus (RSV)-Associated Medically Attended Lower Respiratory Infection (MALRI)
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 sample. Per protocol, the participants with outpatient and inpatient RSV-associated MALRI were reported together for RSV season 1 participants.
Time frame: From Day 1 (postdose) to Day 150
Population: All randomized participants who received a dose of study treatment and were protocol compliant.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| RSV Season 1: Clesrovimab 105 mg | RSV Season 1: Number of Participants With Respiratory Syncytial Virus (RSV)-Associated Medically Attended Lower Respiratory Infection (MALRI) | 60 Participants |
| RSV Season 1: Placebo | RSV Season 1: Number of Participants With Respiratory Syncytial Virus (RSV)-Associated Medically Attended Lower Respiratory Infection (MALRI) | 74 Participants |
p-value: <0.00195% CI: [44.1, 71.9]Exact method
Primary
RSV Season 1: Percentage of Participants With ≥1 Nonserious AE
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. Per protocol, the percentage of RSV season 1 participants with ≥1 nonserious AE were reported.
Time frame: From Day 1 (postdose) to Day 42
Population: Safety analysis population included all randomized participants who received a dose of protocol specified study treatment. Per protocol, in the safety analysis population, participants with protocol deviation were excluded.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RSV Season 1: Clesrovimab 105 mg | RSV Season 1: Percentage of Participants With ≥1 Nonserious AE | 72.8 Percentage of participants |
| RSV Season 1: Placebo | RSV Season 1: Percentage of Participants With ≥1 Nonserious AE | 74.2 Percentage of participants |
Primary
RSV Season 1: Percentage of Participants With Anaphylaxis/Hypersensitivity AE of Special Interest (AESI)
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. Anaphylaxis/Hypersensitivity AESI included anaphylaxis, angioedema, bronchospasm, drug hypersensitivity, dyspnea, hypersensitivity, dysphonia, and wheezing. Per protocol, the percentage of RSV season 1 participants with anaphylaxis/hypersensitivity AESI were reported.
Time frame: From Day 1 (postdose) to Day 42
Population: Safety analysis population included all randomized participants who received a dose of protocol specified study treatment. Per protocol, in the safety analysis population, participants with protocol deviation were excluded.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RSV Season 1: Clesrovimab 105 mg | RSV Season 1: Percentage of Participants With Anaphylaxis/Hypersensitivity AE of Special Interest (AESI) | 0.0 Percentage of participants |
| RSV Season 1: Placebo | RSV Season 1: Percentage of Participants With Anaphylaxis/Hypersensitivity AE of Special Interest (AESI) | 0.0 Percentage of participants |
95% CI: [-0.3, 0.2]
Primary
RSV Season 1: Percentage of Participants With Fever
Fever was defined as rectal temperature ≥102.2°F (≥39.0°C) or axillary temperature ≥101.7°F (≥38.7°C). Per protocol, the percentage of RSV season 1 participants with fever were reported.
Time frame: From Day 1 (postdose) to Day 5
Population: Safety analysis population included all randomized participants who received a dose of protocol specified study treatment and had temperature data available. Per protocol, in the safety analysis population, participants with protocol deviation were excluded.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RSV Season 1: Clesrovimab 105 mg | RSV Season 1: Percentage of Participants With Fever | 0.5 Percentage of participants |
| RSV Season 1: Placebo | RSV Season 1: Percentage of Participants With Fever | 1.2 Percentage of participants |
95% CI: [-1.4, 0]
Primary
RSV Season 1: Percentage of Participants With Rash AESI
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 acute generalized exanthematous pustulosis, drug eruption, drug reaction with eosinophilia and systemic symptoms, erythema multiforme, generalized rash of exfoliative nature, Stevens-Johnson syndrome, toxic epidermal necrolysis, and urticaria. Per protocol, the percentage of RSV season 1 participants with rash AESI were reported.
Time frame: From Day 1 (postdose) to Day 42
Population: Safety analysis population included all randomized participants who received a dose of protocol specified study treatment. Per protocol, in the safety analysis population, participants with protocol deviation were excluded.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RSV Season 1: Clesrovimab 105 mg | RSV Season 1: Percentage of Participants With Rash AESI | 0.5 Percentage of participants |
| RSV Season 1: Placebo | RSV Season 1: Percentage of Participants With Rash AESI | 0.3 Percentage of participants |
95% CI: [-0.4, 0.5]
Primary
RSV Season 1: Percentage of Participants With Solicited Injection-Site Adverse Events (AEs)
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. Solicited injection-site AEs included redness/erythema, swelling, and pain/tenderness. Per protocol, the percentage of RSV season 1 participants with solicited injection-site AEs were reported.
Time frame: From Day 1 (postdose) to Day 5
Population: Safety analysis population included all randomized participants who received a dose of protocol specified study treatment. Per protocol, in the safety analysis population, participants with protocol deviation were excluded.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RSV Season 1: Clesrovimab 105 mg | RSV Season 1: Percentage of Participants With Solicited Injection-Site Adverse Events (AEs) | 9.3 Percentage of participants |
| RSV Season 1: Placebo | RSV Season 1: Percentage of Participants With Solicited Injection-Site Adverse Events (AEs) | 9.7 Percentage of participants |
95% CI: [-2.6, 1.5]
Primary
RSV Season 1: Percentage of Participants With Solicited Systemic AEs
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. Solicited systemic AEs included irritability, somnolence/drowsiness, and appetite lost. Per protocol, the percentage of RSV season 1 participants with solicited systemic AEs were reported.
Time frame: From Day 1 (postdose) to Day 5
Population: Safety analysis population included all randomized participants who received a dose of protocol specified study treatment. Per protocol, in the safety analysis population, participants with protocol deviation were excluded.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RSV Season 1: Clesrovimab 105 mg | RSV Season 1: Percentage of Participants With Solicited Systemic AEs | 26.2 Percentage of participants |
| RSV Season 1: Placebo | RSV Season 1: Percentage of Participants With Solicited Systemic AEs | 28.0 Percentage of participants |
95% CI: [-5, 1.2]
Secondary
RSV Season 1: Number of Participants With RSV-Associated Hospitalization
RSV-associated hospitalization is defined as a hospital admission for respiratory illness and RSV-positive RT-PCR nasopharyngeal sample. Per protocol, the number of participants with RSV-associated hospitalization were reported for RSV season 1.
Time frame: From Day 1 (postdose) to Day 150
Population: All randomized participants who received a dose of study treatment and were protocol compliant.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| RSV Season 1: Clesrovimab 105 mg | RSV Season 1: Number of Participants With RSV-Associated Hospitalization | 9 Participants |
| RSV Season 1: Placebo | RSV Season 1: Number of Participants With RSV-Associated Hospitalization | 28 Participants |
p-value: <0.00195% CI: [66.6, 92.6]Exact method
Secondary
RSV Season 1: Number of Participants With RSV-Associated MALRI
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 RT-PCR nasopharyngeal sample. Per protocol, participants with outpatient and inpatient RSV-associated MALRI were reported together for RSV season 1 participants.
Time frame: From Day 1 (postdose) to Day 180
Population: All randomized participants who received a dose of study treatment and were protocol compliant.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| RSV Season 1: Clesrovimab 105 mg | RSV Season 1: Number of Participants With RSV-Associated MALRI | 64 Participants |
| RSV Season 1: Placebo | RSV Season 1: Number of Participants With RSV-Associated MALRI | 77 Participants |
95% CI: [43.3, 71.1]