Respiratory Tract Infection, Respiratory Syncytial Virus
Conditions
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.
Interventions
DRUGClesrovimab
Single ascending doses of clesrovimab will be administered via IM injection.
DRUGPlacebo
Placebo (0.9% sodium chloride \[NaCl\]) will be administered via IM injection.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Intervention model description
Single ascending dose
Eligibility
Sex/Gender
ALL
Age
2 Weeks to 8 Months
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Experienced At Least One Solicited Injection Site Adverse Event (AE) | 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. |
| Percentage of Participants Who Experienced At Least One Solicited Systemic Adverse Event (AE) | 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. |
| Percentage of Participants Who Experienced At Least One Serious Adverse Event (SAE) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Apparent Terminal Half-life (t1/2) of Clesrovimab | 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. |
| Serum Concentration of Clesrovimab on Day 7 (C7days) | Day 7 | Serum concentration of clesrovimab was measured on Day 7. |
| Serum Concentration of Clesrovimab on Day 14 (C14days) | Day 14 | Serum concentration of clesrovimab was measured on Day 14. |
| Area Under the Serum-Concentration Time Curve From Zero to Infinity (AUC0-∞) | 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. |
| Serum Concentration of Clesrovimab on Day 150 (C150days) | Day 150 | Serum concentration of clesrovimab was measured on Day 150. |
| Serum Concentration of Clesrovimab on Day 365 (C365days) | Day 365 | Serum concentration of clesrovimab was measured on Day 365. |
| Number of Participants With Positive Titer of Anti-Drug Antibodies (ADAs) for Clesrovimab: Panels A, B, C, D1, D2, E1, and E2 | Days 14, 90, 150, 365 and 545 | ADA was assessed at 2 or 3 of the following timepoints for each participant: Days 14, 90, 150, 365 and 545. ADA status for each participant was determined across the timepoints assessed. The definitions of the categories are as follows: (1) ADA Negative: participants whose ADA results were negative at all timepoints measured; (2) Non-treatment emergent positive: participants whose ADA result was positive only at baseline or if postdose titer increased by less than 2-fold relative to the baseline titer; (3) Positive response to MK-1654: participants whose ADA result was negative at baseline and positive at one or more postdose timepoints or participants whose ADA result was positive at baseline and postdose titer increased by greater than or equal to 2-fold relative to the baseline titer. |
| Serum Concentration of Clesrovimab on Day 90 (C90days) | Day 90 | Serum concentration of clesrovimab was measured on Day 90. |
| Maximum Serum Concentration (Cmax) of Clesrovimab | At designated time points (up to 1 year post-dose) | Cmax is the highest observed serum drug concentration. |
| Time to Maximum Serum Concentration (Tmax) of Clesrovimab | 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. |
Countries
Chile, Colombia, South Africa, South Korea, Spain, United States
Participant flow
Recruitment details
183 participants were randomized and 181 were dosed and included in the All Participants as Treated (APaT) population. Two participants who were randomized to the MK-1654 20 mg dose group actually received MK-1654 50 mg and were included in the MK-1654 50 mg group for safety, pharmacokinetic (PK) and immunogenicity analyses.
Pre-assignment details
Participants enrolled in panels D and E prior to protocol amendment 04 who chose not to participate in the modified schedule followed the D1 and E1 schedule of activities. Participants enrolled in panels D and E prior to protocol amendment 04 who chose to participate in the modified schedule followed the D2 and E2 schedule of activities.
Participants by arm
| Arm | Count |
|---|---|
| Panel A: Preterm Clesrovimab 20mg Pre-term infants received clesrovimab 20mg via intramuscular (IM) injection and were followed for up to 365 days. | 8 |
| Panel B: Pre-term Clesrovimab 50mg Pre-term infants received clesrovimab 50mg via IM injection and were followed for up to 365 days. | 31 |
| Panel C: Pre-term Clesrovimab 75mg Pre-term infants received clesrovimab 75mg via IM injection and were followed for up to 365 days. | 41 |
| Panel D1 and D2: Pre-term Clesrovimab 100mg Pre-term infants received clesrovimab 100mg via IM injection and were followed for up to 365 and 545 days. | 32 |
| Panel E1 and E2: Full-term Clesrovimab 100mg Full-term infants received clesrovimab 100mg via IM injection and were followed for up to 365 and 545 days. | 33 |
| Placebo Pre-term and Full-term infants received placebo via IM injection. | 38 |
| Total | 183 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Other | 0 | 1 | 0 | 0 | 1 | 1 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 0 | 1 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Parent/Guardian | 0 | 1 | 0 | 1 | 3 | 0 |
Baseline characteristics
| Characteristic | Panel A: Preterm Clesrovimab 20mg | Panel B: Pre-term Clesrovimab 50mg | Panel C: Pre-term Clesrovimab 75mg | Panel D1 and D2: Pre-term Clesrovimab 100mg | Panel E1 and E2: Full-term Clesrovimab 100mg | Placebo | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 68.0 days | 109.0 days | 94.0 days | 139.5 days | 164.0 days | 128.0 days | 126.0 days |
| Age, Customized 85 years and over | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Adolescents (12-17 years) | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Adults (18-64 years) | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Children (2-11 years) | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized From 65-84 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Infants and toddlers (28 days-23 months) | 8 Participants | 29 Participants | 38 Participants | 29 Participants | 33 Participants | 36 Participants | 173 Participants |
| Age, Customized In utero | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Newborns (0-27 days) | 0 Participants | 2 Participants | 3 Participants | 3 Participants | 0 Participants | 2 Participants | 10 Participants |
| Age, Customized Preterm newborn infants (gestational age < 37 wks) | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 12 Participants | 25 Participants | 9 Participants | 14 Participants | 18 Participants | 79 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 19 Participants | 16 Participants | 23 Participants | 19 Participants | 20 Participants | 104 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 5 Participants | 0 Participants | 0 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 8 Participants | 9 Participants | 14 Participants | 14 Participants | 11 Participants | 60 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 17 Participants | 2 Participants | 7 Participants | 9 Participants | 36 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) White | 4 Participants | 20 Participants | 14 Participants | 8 Participants | 11 Participants | 14 Participants | 71 Participants |
| Sex: Female, Male Female | 6 Participants | 15 Participants | 20 Participants | 17 Participants | 13 Participants | 19 Participants | 90 Participants |
| Sex: Female, Male Male | 2 Participants | 16 Participants | 21 Participants | 15 Participants | 20 Participants | 19 Participants | 93 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 31 | 0 / 41 | 0 / 32 | 0 / 33 | 0 / 38 |
| other Total, other adverse events | 6 / 6 | 29 / 33 | 29 / 40 | 26 / 32 | 29 / 32 | 33 / 38 |
| serious Total, serious adverse events | 1 / 6 | 4 / 33 | 1 / 40 | 3 / 32 | 6 / 32 | 6 / 38 |
Outcome results
Primary
Percentage of Participants Who Experienced At Least One Serious Adverse Event (SAE)
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.
Time frame: Up to Day 545
Population: Safety analysis population consisted of all participants who received at least one dose of study treatment. Two participants who were randomized to the MK-1654 Panel A 20 mg dose group actually received MK-1654 Panel B 50mg and were included in the MK-1654 50 mg group for the protocol specified safety analysis population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Panel A: Preterm Clesrovimab 20mg | Percentage of Participants Who Experienced At Least One Serious Adverse Event (SAE) | with serious adverse events (SAE) | 1 Participants |
| Panel A: Preterm Clesrovimab 20mg | Percentage of Participants Who Experienced At Least One Serious Adverse Event (SAE) | without SAE | 5 Participants |
| Panel B: Pre-term Clesrovimab 50mg | Percentage of Participants Who Experienced At Least One Serious Adverse Event (SAE) | with serious adverse events (SAE) | 4 Participants |
| Panel B: Pre-term Clesrovimab 50mg | Percentage of Participants Who Experienced At Least One Serious Adverse Event (SAE) | without SAE | 29 Participants |
| Panel C: Pre-term Clesrovimab 75mg | Percentage of Participants Who Experienced At Least One Serious Adverse Event (SAE) | with serious adverse events (SAE) | 1 Participants |
| Panel C: Pre-term Clesrovimab 75mg | Percentage of Participants Who Experienced At Least One Serious Adverse Event (SAE) | without SAE | 39 Participants |
| Panel D1 and D2: Pre-term Clesrovimab 100mg | Percentage of Participants Who Experienced At Least One Serious Adverse Event (SAE) | with serious adverse events (SAE) | 3 Participants |
| Panel D1 and D2: Pre-term Clesrovimab 100mg | Percentage of Participants Who Experienced At Least One Serious Adverse Event (SAE) | without SAE | 29 Participants |
| Panel E1 and E2: Full-term Clesrovimab 100mg | Percentage of Participants Who Experienced At Least One Serious Adverse Event (SAE) | with serious adverse events (SAE) | 6 Participants |
| Panel E1 and E2: Full-term Clesrovimab 100mg | Percentage of Participants Who Experienced At Least One Serious Adverse Event (SAE) | without SAE | 26 Participants |
| Placebo | Percentage of Participants Who Experienced At Least One Serious Adverse Event (SAE) | with serious adverse events (SAE) | 6 Participants |
| Placebo | Percentage of Participants Who Experienced At Least One Serious Adverse Event (SAE) | without SAE | 32 Participants |
Primary
Percentage of Participants Who Experienced At Least One Solicited Injection Site Adverse Event (AE)
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.
Time frame: Up to Day 5
Population: Safety analysis population consisted of all participants who received at least one dose of study treatment. Two participants who were randomized to the MK-1654 Panel A 20 mg dose group actually received MK-1654 Panel B 50mg and were included in the MK-1654 50 mg group for the protocol specified safety analysis population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Panel A: Preterm Clesrovimab 20mg | Percentage of Participants Who Experienced At Least One Solicited Injection Site Adverse Event (AE) | with solicited injection site adverse events | 3 Participants |
| Panel A: Preterm Clesrovimab 20mg | Percentage of Participants Who Experienced At Least One Solicited Injection Site Adverse Event (AE) | without solicited injection site adverse events | 3 Participants |
| Panel B: Pre-term Clesrovimab 50mg | Percentage of Participants Who Experienced At Least One Solicited Injection Site Adverse Event (AE) | with solicited injection site adverse events | 3 Participants |
| Panel B: Pre-term Clesrovimab 50mg | Percentage of Participants Who Experienced At Least One Solicited Injection Site Adverse Event (AE) | without solicited injection site adverse events | 30 Participants |
| Panel C: Pre-term Clesrovimab 75mg | Percentage of Participants Who Experienced At Least One Solicited Injection Site Adverse Event (AE) | with solicited injection site adverse events | 3 Participants |
| Panel C: Pre-term Clesrovimab 75mg | Percentage of Participants Who Experienced At Least One Solicited Injection Site Adverse Event (AE) | without solicited injection site adverse events | 37 Participants |
| Panel D1 and D2: Pre-term Clesrovimab 100mg | Percentage of Participants Who Experienced At Least One Solicited Injection Site Adverse Event (AE) | with solicited injection site adverse events | 2 Participants |
| Panel D1 and D2: Pre-term Clesrovimab 100mg | Percentage of Participants Who Experienced At Least One Solicited Injection Site Adverse Event (AE) | without solicited injection site adverse events | 30 Participants |
| Panel E1 and E2: Full-term Clesrovimab 100mg | Percentage of Participants Who Experienced At Least One Solicited Injection Site Adverse Event (AE) | with solicited injection site adverse events | 2 Participants |
| Panel E1 and E2: Full-term Clesrovimab 100mg | Percentage of Participants Who Experienced At Least One Solicited Injection Site Adverse Event (AE) | without solicited injection site adverse events | 30 Participants |
| Placebo | Percentage of Participants Who Experienced At Least One Solicited Injection Site Adverse Event (AE) | with solicited injection site adverse events | 2 Participants |
| Placebo | Percentage of Participants Who Experienced At Least One Solicited Injection Site Adverse Event (AE) | without solicited injection site adverse events | 36 Participants |
Primary
Percentage of Participants Who Experienced At Least One Solicited Systemic Adverse Event (AE)
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.
Time frame: Up to Day 5
Population: Safety analysis population consisted of all participants who received at least one dose of study treatment. Two participants who were randomized to the MK-1654 Panel A 20 mg dose group actually received MK-1654 Panel B 50mg and were included in the MK-1654 50 mg group for the protocol specified safety analysis population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Panel A: Preterm Clesrovimab 20mg | Percentage of Participants Who Experienced At Least One Solicited Systemic Adverse Event (AE) | with solicited systemic adverse events | 2 Participants |
| Panel A: Preterm Clesrovimab 20mg | Percentage of Participants Who Experienced At Least One Solicited Systemic Adverse Event (AE) | without solicited systemic adverse events | 4 Participants |
| Panel B: Pre-term Clesrovimab 50mg | Percentage of Participants Who Experienced At Least One Solicited Systemic Adverse Event (AE) | with solicited systemic adverse events | 8 Participants |
| Panel B: Pre-term Clesrovimab 50mg | Percentage of Participants Who Experienced At Least One Solicited Systemic Adverse Event (AE) | without solicited systemic adverse events | 25 Participants |
| Panel C: Pre-term Clesrovimab 75mg | Percentage of Participants Who Experienced At Least One Solicited Systemic Adverse Event (AE) | with solicited systemic adverse events | 9 Participants |
| Panel C: Pre-term Clesrovimab 75mg | Percentage of Participants Who Experienced At Least One Solicited Systemic Adverse Event (AE) | without solicited systemic adverse events | 31 Participants |
| Panel D1 and D2: Pre-term Clesrovimab 100mg | Percentage of Participants Who Experienced At Least One Solicited Systemic Adverse Event (AE) | with solicited systemic adverse events | 2 Participants |
| Panel D1 and D2: Pre-term Clesrovimab 100mg | Percentage of Participants Who Experienced At Least One Solicited Systemic Adverse Event (AE) | without solicited systemic adverse events | 30 Participants |
| Panel E1 and E2: Full-term Clesrovimab 100mg | Percentage of Participants Who Experienced At Least One Solicited Systemic Adverse Event (AE) | with solicited systemic adverse events | 3 Participants |
| Panel E1 and E2: Full-term Clesrovimab 100mg | Percentage of Participants Who Experienced At Least One Solicited Systemic Adverse Event (AE) | without solicited systemic adverse events | 29 Participants |
| Placebo | Percentage of Participants Who Experienced At Least One Solicited Systemic Adverse Event (AE) | with solicited systemic adverse events | 9 Participants |
| Placebo | Percentage of Participants Who Experienced At Least One Solicited Systemic Adverse Event (AE) | without solicited systemic adverse events | 29 Participants |
Secondary
Apparent Terminal Half-life (t1/2) of Clesrovimab
t1/2 is the time required for 50% of drug to be cleared from serum.
Time frame: At designated time points (up to 1 year post-dose)
Population: All randomized participants who received at least one dose of study treatment, with exclusions for important protocol deviations that may have substantially affected the results and with data available for this outcome measure. Two participants who were randomized to the MK-1654 Panel A 20 mg dose group actually received MK-1654 Panel B 50mg and were included in the MK-1654 50 mg group for the protocol specified PK analysis population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Panel A: Preterm Clesrovimab 20mg | Apparent Terminal Half-life (t1/2) of Clesrovimab | 48.8 day | Geometric Coefficient of Variation 34.6 |
| Panel B: Pre-term Clesrovimab 50mg | Apparent Terminal Half-life (t1/2) of Clesrovimab | 44.6 day | Geometric Coefficient of Variation 10.9 |
| Panel C: Pre-term Clesrovimab 75mg | Apparent Terminal Half-life (t1/2) of Clesrovimab | 46.1 day | Geometric Coefficient of Variation 15.1 |
| Panel D1 and D2: Pre-term Clesrovimab 100mg | Apparent Terminal Half-life (t1/2) of Clesrovimab | 45.2 day | Geometric Coefficient of Variation 13.7 |
| Panel E1 and E2: Full-term Clesrovimab 100mg | Apparent Terminal Half-life (t1/2) of Clesrovimab | 43.0 day | Geometric Coefficient of Variation 9.72 |
Secondary
Area Under the Serum-Concentration Time Curve From Zero to Infinity (AUC0-∞)
AUC0-∞ is a measure of the extrapolated mean concentration in serum from dosing to infinity.
Time frame: At designated time points (up to 1 year post-dose)
Population: All randomized participants who received at least one dose of study treatment, with exclusions for important protocol deviations that may have substantially affected the results and with data available for this outcome measure. Two participants who were randomized to the MK-1654 Panel A 20 mg dose group actually received MK-1654 Panel B 50mg and were included in the MK-1654 50 mg group for the protocol specified PK analysis population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Panel A: Preterm Clesrovimab 20mg | Area Under the Serum-Concentration Time Curve From Zero to Infinity (AUC0-∞) | 1560 day*μg/mL | Geometric Coefficient of Variation 43.5 |
| Panel B: Pre-term Clesrovimab 50mg | Area Under the Serum-Concentration Time Curve From Zero to Infinity (AUC0-∞) | 3520 day*μg/mL | Geometric Coefficient of Variation 22.8 |
| Panel C: Pre-term Clesrovimab 75mg | Area Under the Serum-Concentration Time Curve From Zero to Infinity (AUC0-∞) | 5510 day*μg/mL | Geometric Coefficient of Variation 22.4 |
| Panel D1 and D2: Pre-term Clesrovimab 100mg | Area Under the Serum-Concentration Time Curve From Zero to Infinity (AUC0-∞) | 6790 day*μg/mL | Geometric Coefficient of Variation 25.4 |
| Panel E1 and E2: Full-term Clesrovimab 100mg | Area Under the Serum-Concentration Time Curve From Zero to Infinity (AUC0-∞) | 5690 day*μg/mL | Geometric Coefficient of Variation 15.9 |
Secondary
Maximum Serum Concentration (Cmax) of Clesrovimab
Cmax is the highest observed serum drug concentration.
Time frame: At designated time points (up to 1 year post-dose)
Population: All randomized participants who received at least one dose of study treatment, with exclusions for important protocol deviations that may have substantially affected the results and with data available for this outcome measure. Two participants who were randomized to the MK-1654 Panel A 20 mg dose group actually received MK-1654 Panel B 50mg and were included in the MK-1654 50 mg group for the protocol specified PK analysis population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Panel A: Preterm Clesrovimab 20mg | Maximum Serum Concentration (Cmax) of Clesrovimab | 26.3 μg/mL | Geometric Coefficient of Variation 19.3 |
| Panel B: Pre-term Clesrovimab 50mg | Maximum Serum Concentration (Cmax) of Clesrovimab | 61.7 μg/mL | Geometric Coefficient of Variation 21.8 |
| Panel C: Pre-term Clesrovimab 75mg | Maximum Serum Concentration (Cmax) of Clesrovimab | 94.5 μg/mL | Geometric Coefficient of Variation 20.5 |
| Panel D1 and D2: Pre-term Clesrovimab 100mg | Maximum Serum Concentration (Cmax) of Clesrovimab | 117 μg/mL | Geometric Coefficient of Variation 23.5 |
| Panel E1 and E2: Full-term Clesrovimab 100mg | Maximum Serum Concentration (Cmax) of Clesrovimab | 99.9 μg/mL | Geometric Coefficient of Variation 13.7 |
Secondary
Number of Participants With Positive Titer of Anti-Drug Antibodies (ADAs) for Clesrovimab: Panels A, B, C, D1, D2, E1, and E2
ADA was assessed at 2 or 3 of the following timepoints for each participant: Days 14, 90, 150, 365 and 545. ADA status for each participant was determined across the timepoints assessed. The definitions of the categories are as follows: (1) ADA Negative: participants whose ADA results were negative at all timepoints measured; (2) Non-treatment emergent positive: participants whose ADA result was positive only at baseline or if postdose titer increased by less than 2-fold relative to the baseline titer; (3) Positive response to MK-1654: participants whose ADA result was negative at baseline and positive at one or more postdose timepoints or participants whose ADA result was positive at baseline and postdose titer increased by greater than or equal to 2-fold relative to the baseline titer.
Time frame: Days 14, 90, 150, 365 and 545
Population: All randomized participants who received at least one dose of study treatment and were evaluable with at least one ADA result after treatment with MK-1654. Two participants who were randomized to the MK-1654 Panel A 20 mg dose group actually received MK-1654 Panel B 50 mg and were included in the MK-1654 50 mg group for the protocol specified immunogenicity analysis population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Panel A: Preterm Clesrovimab 20mg | Number of Participants With Positive Titer of Anti-Drug Antibodies (ADAs) for Clesrovimab: Panels A, B, C, D1, D2, E1, and E2 | ADA Negative status | 4 Participants |
| Panel A: Preterm Clesrovimab 20mg | Number of Participants With Positive Titer of Anti-Drug Antibodies (ADAs) for Clesrovimab: Panels A, B, C, D1, D2, E1, and E2 | Maximum Postdose Titer of 9285 to 160000 of ADA | 2 Participants |
| Panel A: Preterm Clesrovimab 20mg | Number of Participants With Positive Titer of Anti-Drug Antibodies (ADAs) for Clesrovimab: Panels A, B, C, D1, D2, E1, and E2 | Maximum Postdose Titer of 1077.5 to < 9285 of ADA | 0 Participants |
| Panel A: Preterm Clesrovimab 20mg | Number of Participants With Positive Titer of Anti-Drug Antibodies (ADAs) for Clesrovimab: Panels A, B, C, D1, D2, E1, and E2 | ADA Positive response to MK-1654 | 2 Participants |
| Panel A: Preterm Clesrovimab 20mg | Number of Participants With Positive Titer of Anti-Drug Antibodies (ADAs) for Clesrovimab: Panels A, B, C, D1, D2, E1, and E2 | Non-treatment emergent positive | 0 Participants |
| Panel A: Preterm Clesrovimab 20mg | Number of Participants With Positive Titer of Anti-Drug Antibodies (ADAs) for Clesrovimab: Panels A, B, C, D1, D2, E1, and E2 | Maximum Postdose Titer of 20 to < 189 of ADA | 0 Participants |
| Panel A: Preterm Clesrovimab 20mg | Number of Participants With Positive Titer of Anti-Drug Antibodies (ADAs) for Clesrovimab: Panels A, B, C, D1, D2, E1, and E2 | Maximum Postdose Titer of 189 to < 1077.5 of ADA | 0 Participants |
| Panel B: Pre-term Clesrovimab 50mg | Number of Participants With Positive Titer of Anti-Drug Antibodies (ADAs) for Clesrovimab: Panels A, B, C, D1, D2, E1, and E2 | Maximum Postdose Titer of 189 to < 1077.5 of ADA | 1 Participants |
| Panel B: Pre-term Clesrovimab 50mg | Number of Participants With Positive Titer of Anti-Drug Antibodies (ADAs) for Clesrovimab: Panels A, B, C, D1, D2, E1, and E2 | Maximum Postdose Titer of 20 to < 189 of ADA | 6 Participants |
| Panel B: Pre-term Clesrovimab 50mg | Number of Participants With Positive Titer of Anti-Drug Antibodies (ADAs) for Clesrovimab: Panels A, B, C, D1, D2, E1, and E2 | Non-treatment emergent positive | 0 Participants |
| Panel B: Pre-term Clesrovimab 50mg | Number of Participants With Positive Titer of Anti-Drug Antibodies (ADAs) for Clesrovimab: Panels A, B, C, D1, D2, E1, and E2 | ADA Negative status | 23 Participants |
| Panel B: Pre-term Clesrovimab 50mg | Number of Participants With Positive Titer of Anti-Drug Antibodies (ADAs) for Clesrovimab: Panels A, B, C, D1, D2, E1, and E2 | Maximum Postdose Titer of 1077.5 to < 9285 of ADA | 0 Participants |
| Panel B: Pre-term Clesrovimab 50mg | Number of Participants With Positive Titer of Anti-Drug Antibodies (ADAs) for Clesrovimab: Panels A, B, C, D1, D2, E1, and E2 | ADA Positive response to MK-1654 | 9 Participants |
| Panel B: Pre-term Clesrovimab 50mg | Number of Participants With Positive Titer of Anti-Drug Antibodies (ADAs) for Clesrovimab: Panels A, B, C, D1, D2, E1, and E2 | Maximum Postdose Titer of 9285 to 160000 of ADA | 2 Participants |
| Panel C: Pre-term Clesrovimab 75mg | Number of Participants With Positive Titer of Anti-Drug Antibodies (ADAs) for Clesrovimab: Panels A, B, C, D1, D2, E1, and E2 | Maximum Postdose Titer of 20 to < 189 of ADA | 2 Participants |
| Panel C: Pre-term Clesrovimab 75mg | Number of Participants With Positive Titer of Anti-Drug Antibodies (ADAs) for Clesrovimab: Panels A, B, C, D1, D2, E1, and E2 | ADA Negative status | 35 Participants |
| Panel C: Pre-term Clesrovimab 75mg | Number of Participants With Positive Titer of Anti-Drug Antibodies (ADAs) for Clesrovimab: Panels A, B, C, D1, D2, E1, and E2 | Non-treatment emergent positive | 0 Participants |
| Panel C: Pre-term Clesrovimab 75mg | Number of Participants With Positive Titer of Anti-Drug Antibodies (ADAs) for Clesrovimab: Panels A, B, C, D1, D2, E1, and E2 | ADA Positive response to MK-1654 | 4 Participants |
| Panel C: Pre-term Clesrovimab 75mg | Number of Participants With Positive Titer of Anti-Drug Antibodies (ADAs) for Clesrovimab: Panels A, B, C, D1, D2, E1, and E2 | Maximum Postdose Titer of 189 to < 1077.5 of ADA | 1 Participants |
| Panel C: Pre-term Clesrovimab 75mg | Number of Participants With Positive Titer of Anti-Drug Antibodies (ADAs) for Clesrovimab: Panels A, B, C, D1, D2, E1, and E2 | Maximum Postdose Titer of 1077.5 to < 9285 of ADA | 1 Participants |
| Panel C: Pre-term Clesrovimab 75mg | Number of Participants With Positive Titer of Anti-Drug Antibodies (ADAs) for Clesrovimab: Panels A, B, C, D1, D2, E1, and E2 | Maximum Postdose Titer of 9285 to 160000 of ADA | 0 Participants |
| Panel D1 and D2: Pre-term Clesrovimab 100mg | Number of Participants With Positive Titer of Anti-Drug Antibodies (ADAs) for Clesrovimab: Panels A, B, C, D1, D2, E1, and E2 | ADA Positive response to MK-1654 | 16 Participants |
| Panel D1 and D2: Pre-term Clesrovimab 100mg | Number of Participants With Positive Titer of Anti-Drug Antibodies (ADAs) for Clesrovimab: Panels A, B, C, D1, D2, E1, and E2 | Maximum Postdose Titer of 189 to < 1077.5 of ADA | 3 Participants |
| Panel D1 and D2: Pre-term Clesrovimab 100mg | Number of Participants With Positive Titer of Anti-Drug Antibodies (ADAs) for Clesrovimab: Panels A, B, C, D1, D2, E1, and E2 | Non-treatment emergent positive | 1 Participants |
| Panel D1 and D2: Pre-term Clesrovimab 100mg | Number of Participants With Positive Titer of Anti-Drug Antibodies (ADAs) for Clesrovimab: Panels A, B, C, D1, D2, E1, and E2 | Maximum Postdose Titer of 9285 to 160000 of ADA | 4 Participants |
| Panel D1 and D2: Pre-term Clesrovimab 100mg | Number of Participants With Positive Titer of Anti-Drug Antibodies (ADAs) for Clesrovimab: Panels A, B, C, D1, D2, E1, and E2 | Maximum Postdose Titer of 1077.5 to < 9285 of ADA | 4 Participants |
| Panel D1 and D2: Pre-term Clesrovimab 100mg | Number of Participants With Positive Titer of Anti-Drug Antibodies (ADAs) for Clesrovimab: Panels A, B, C, D1, D2, E1, and E2 | ADA Negative status | 15 Participants |
| Panel D1 and D2: Pre-term Clesrovimab 100mg | Number of Participants With Positive Titer of Anti-Drug Antibodies (ADAs) for Clesrovimab: Panels A, B, C, D1, D2, E1, and E2 | Maximum Postdose Titer of 20 to < 189 of ADA | 4 Participants |
| Panel E1 and E2: Full-term Clesrovimab 100mg | Number of Participants With Positive Titer of Anti-Drug Antibodies (ADAs) for Clesrovimab: Panels A, B, C, D1, D2, E1, and E2 | ADA Positive response to MK-1654 | 20 Participants |
| Panel E1 and E2: Full-term Clesrovimab 100mg | Number of Participants With Positive Titer of Anti-Drug Antibodies (ADAs) for Clesrovimab: Panels A, B, C, D1, D2, E1, and E2 | Maximum Postdose Titer of 9285 to 160000 of ADA | 4 Participants |
| Panel E1 and E2: Full-term Clesrovimab 100mg | Number of Participants With Positive Titer of Anti-Drug Antibodies (ADAs) for Clesrovimab: Panels A, B, C, D1, D2, E1, and E2 | Maximum Postdose Titer of 1077.5 to < 9285 of ADA | 7 Participants |
| Panel E1 and E2: Full-term Clesrovimab 100mg | Number of Participants With Positive Titer of Anti-Drug Antibodies (ADAs) for Clesrovimab: Panels A, B, C, D1, D2, E1, and E2 | Maximum Postdose Titer of 189 to < 1077.5 of ADA | 7 Participants |
| Panel E1 and E2: Full-term Clesrovimab 100mg | Number of Participants With Positive Titer of Anti-Drug Antibodies (ADAs) for Clesrovimab: Panels A, B, C, D1, D2, E1, and E2 | Non-treatment emergent positive | 1 Participants |
| Panel E1 and E2: Full-term Clesrovimab 100mg | Number of Participants With Positive Titer of Anti-Drug Antibodies (ADAs) for Clesrovimab: Panels A, B, C, D1, D2, E1, and E2 | ADA Negative status | 9 Participants |
| Panel E1 and E2: Full-term Clesrovimab 100mg | Number of Participants With Positive Titer of Anti-Drug Antibodies (ADAs) for Clesrovimab: Panels A, B, C, D1, D2, E1, and E2 | Maximum Postdose Titer of 20 to < 189 of ADA | 2 Participants |
Secondary
Serum Concentration of Clesrovimab on Day 14 (C14days)
Serum concentration of clesrovimab was measured on Day 14.
Time frame: Day 14
Population: All randomized participants who received at least one dose of study treatment, with exclusions for important protocol deviations that may have substantially affected the results and with data available for this outcome measure. Two participants who were randomized to the MK-1654 Panel A 20 mg dose group actually received MK-1654 Panel B 50mg and were included in the MK-1654 50 mg group for the protocol specified PK analysis population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Panel A: Preterm Clesrovimab 20mg | Serum Concentration of Clesrovimab on Day 14 (C14days) | 19.4 μg/mL | Geometric Coefficient of Variation 22.1 |
| Panel B: Pre-term Clesrovimab 50mg | Serum Concentration of Clesrovimab on Day 14 (C14days) | 46.8 μg/mL | Geometric Coefficient of Variation 20.6 |
| Panel C: Pre-term Clesrovimab 75mg | Serum Concentration of Clesrovimab on Day 14 (C14days) | 71.1 μg/mL | Geometric Coefficient of Variation 19.7 |
| Panel D1 and D2: Pre-term Clesrovimab 100mg | Serum Concentration of Clesrovimab on Day 14 (C14days) | 88.6 μg/mL | Geometric Coefficient of Variation 21.8 |
| Panel E1 and E2: Full-term Clesrovimab 100mg | Serum Concentration of Clesrovimab on Day 14 (C14days) | 75.4 μg/mL | Geometric Coefficient of Variation 12.9 |
Secondary
Serum Concentration of Clesrovimab on Day 150 (C150days)
Serum concentration of clesrovimab was measured on Day 150.
Time frame: Day 150
Population: All randomized participants who received at least one dose of study treatment, with exclusions for important protocol deviations that may have substantially affected the results and with data available for this outcome measure. Two participants who were randomized to the MK-1654 Panel A 20 mg dose group actually received MK-1654 Panel B 50mg and were included in the MK-1654 50 mg group for the protocol specified PK analysis population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Panel A: Preterm Clesrovimab 20mg | Serum Concentration of Clesrovimab on Day 150 (C150days) | 2.24 μg/mL | Geometric Coefficient of Variation 80.6 |
| Panel B: Pre-term Clesrovimab 50mg | Serum Concentration of Clesrovimab on Day 150 (C150days) | 4.98 μg/mL | Geometric Coefficient of Variation 34.2 |
| Panel C: Pre-term Clesrovimab 75mg | Serum Concentration of Clesrovimab on Day 150 (C150days) | 8.05 μg/mL | Geometric Coefficient of Variation 37.7 |
| Panel D1 and D2: Pre-term Clesrovimab 100mg | Serum Concentration of Clesrovimab on Day 150 (C150days) | 9.70 μg/mL | Geometric Coefficient of Variation 40.2 |
| Panel E1 and E2: Full-term Clesrovimab 100mg | Serum Concentration of Clesrovimab on Day 150 (C150days) | 7.96 μg/mL | Geometric Coefficient of Variation 26.7 |
Secondary
Serum Concentration of Clesrovimab on Day 365 (C365days)
Serum concentration of clesrovimab was measured on Day 365.
Time frame: Day 365
Population: All randomized participants who received at least one dose of study treatment, with exclusions for important protocol deviations that may have substantially affected the results and with data available for this outcome measure. Two participants who were randomized to the MK-1654 Panel A 20 mg dose group actually received MK-1654 Panel B 50mg and were included in the MK-1654 50 mg group for the protocol specified PK analysis population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Panel A: Preterm Clesrovimab 20mg | Serum Concentration of Clesrovimab on Day 365 (C365days) | 0.0953 μg/mL | Geometric Coefficient of Variation 362 |
| Panel B: Pre-term Clesrovimab 50mg | Serum Concentration of Clesrovimab on Day 365 (C365days) | 0.177 μg/mL | Geometric Coefficient of Variation 79.4 |
| Panel C: Pre-term Clesrovimab 75mg | Serum Concentration of Clesrovimab on Day 365 (C365days) | 0.313 μg/mL | Geometric Coefficient of Variation 107 |
| Panel D1 and D2: Pre-term Clesrovimab 100mg | Serum Concentration of Clesrovimab on Day 365 (C365days) | 0.355 μg/mL | Geometric Coefficient of Variation 104 |
| Panel E1 and E2: Full-term Clesrovimab 100mg | Serum Concentration of Clesrovimab on Day 365 (C365days) | 0.248 μg/mL | Geometric Coefficient of Variation 63.1 |
Secondary
Serum Concentration of Clesrovimab on Day 7 (C7days)
Serum concentration of clesrovimab was measured on Day 7.
Time frame: Day 7
Population: All randomized participants who received at least one dose of study treatment, with exclusions for important protocol deviations that may have substantially affected the results and with data available for this outcome measure. Two participants who were randomized to the MK-1654 Panel A 20 mg dose group actually received MK-1654 Panel B 50mg and were included in the MK-1654 50 mg group for the protocol specified PK analysis population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Panel A: Preterm Clesrovimab 20mg | Serum Concentration of Clesrovimab on Day 7 (C7days) | 24.4 μg/mL | Geometric Coefficient of Variation 20.4 |
| Panel B: Pre-term Clesrovimab 50mg | Serum Concentration of Clesrovimab on Day 7 (C7days) | 57.8 μg/mL | Geometric Coefficient of Variation 21.6 |
| Panel C: Pre-term Clesrovimab 75mg | Serum Concentration of Clesrovimab on Day 7 (C7days) | 88.1 μg/mL | Geometric Coefficient of Variation 20.4 |
| Panel D1 and D2: Pre-term Clesrovimab 100mg | Serum Concentration of Clesrovimab on Day 7 (C7days) | 109 μg/mL | Geometric Coefficient of Variation 23 |
| Panel E1 and E2: Full-term Clesrovimab 100mg | Serum Concentration of Clesrovimab on Day 7 (C7days) | 92.8 μg/mL | Geometric Coefficient of Variation 13.3 |
Secondary
Serum Concentration of Clesrovimab on Day 90 (C90days)
Serum concentration of clesrovimab was measured on Day 90.
Time frame: Day 90
Population: All randomized participants who received at least one dose of study treatment, with exclusions for important protocol deviations that may have substantially affected the results and with data available for this outcome measure. Two participants who were randomized to the MK-1654 Panel A 20 mg dose group actually received MK-1654 Panel B 50mg and were included in the MK-1654 50 mg group for the protocol specified PK analysis population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Panel A: Preterm Clesrovimab 20mg | Serum Concentration of Clesrovimab on Day 90 (C90days) | 5.60 μg/mL | Geometric Coefficient of Variation 49.5 |
| Panel B: Pre-term Clesrovimab 50mg | Serum Concentration of Clesrovimab on Day 90 (C90days) | 13.0 μg/mL | Geometric Coefficient of Variation 25.4 |
| Panel C: Pre-term Clesrovimab 75mg | Serum Concentration of Clesrovimab on Day 90 (C90days) | 20.4 μg/mL | Geometric Coefficient of Variation 25.8 |
| Panel D1 and D2: Pre-term Clesrovimab 100mg | Serum Concentration of Clesrovimab on Day 90 (C90days) | 25.2 μg/mL | Geometric Coefficient of Variation 28.6 |
| Panel E1 and E2: Full-term Clesrovimab 100mg | Serum Concentration of Clesrovimab on Day 90 (C90days) | 21.1 μg/mL | Geometric Coefficient of Variation 18.8 |
Secondary
Time to Maximum Serum Concentration (Tmax) of Clesrovimab
Tmax is the time taken to reach the maximum observed plasma (Cmax) concentration of Clesrovimab.
Time frame: At designated time points (up to 1 year post-dose)
Population: All randomized participants who received at least one dose of study treatment, with exclusions for important protocol deviations that may have substantially affected the results and with data available for this outcome measure. Two participants who were randomized to the MK-1654 Panel A 20 mg dose group actually received MK-1654 Panel B 50mg and were included in the MK-1654 50 mg group for the protocol specified PK analysis population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panel A: Preterm Clesrovimab 20mg | Time to Maximum Serum Concentration (Tmax) of Clesrovimab | 4.0 day |
| Panel B: Pre-term Clesrovimab 50mg | Time to Maximum Serum Concentration (Tmax) of Clesrovimab | 4.20 day |
| Panel C: Pre-term Clesrovimab 75mg | Time to Maximum Serum Concentration (Tmax) of Clesrovimab | 4.20 day |
| Panel D1 and D2: Pre-term Clesrovimab 100mg | Time to Maximum Serum Concentration (Tmax) of Clesrovimab | 4.10 day |
| Panel E1 and E2: Full-term Clesrovimab 100mg | Time to Maximum Serum Concentration (Tmax) of Clesrovimab | 4.10 day |