Safety, Tolerability, and Pharmacokinetics of Clesrovimab (MK-1654) in Infants (MK-1654-002)
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| ClinicalTrials.gov Identifier: NCT03524118 |
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Recruitment Status :
Completed
First Posted : May 14, 2018
Last Update Posted : September 27, 2022
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Sponsor:
Merck Sharp & Dohme LLC
Information provided by (Responsible Party):
Merck Sharp & Dohme LLC
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Respiratory Tract Infection Respiratory Syncytial Virus | Drug: Clesrovimab Drug: Placebo | Phase 1 Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 182 participants |
| Allocation: | Randomized |
| Intervention Model: | Sequential Assignment |
| Intervention Model Description: | Single ascending dose |
| Masking: | Triple (Participant, Care Provider, Investigator) |
| Primary Purpose: | Prevention |
| Official Title: | A Double-blind, Randomized, Placebo-controlled, Single Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of MK-1654 in Pre-Term and Full-Term Infants |
| Actual Study Start Date : | September 20, 2018 |
| Actual Primary Completion Date : | September 14, 2022 |
| Actual Study Completion Date : | September 14, 2022 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Panel A: Pre-term clesrovimab Dose 1
Pre-term infants will receive clesrovimab Dose 1 via intramuscular (IM) injection and will be followed for up to 365 days.
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Drug: Clesrovimab
Single ascending doses of clesrovimab will be administered via IM injection.
Other Name: MK-1654 |
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Experimental: Panel B: Pre-term clesrovimab Dose 2
Pre-term infants will receive clesrovimab Dose 2 via IM injection and will be followed for up to 365 days.
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Drug: Clesrovimab
Single ascending doses of clesrovimab will be administered via IM injection.
Other Name: MK-1654 |
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Experimental: Panel C: Pre-term clesrovimab Dose 3
Pre-term infants will receive clesrovimab Dose 3 via IM injection and will be followed for up to 365 days.
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Drug: Clesrovimab
Single ascending doses of clesrovimab will be administered via IM injection.
Other Name: MK-1654 |
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Experimental: Panel D1: Pre-term clesrovimab Dose 4
Pre-term infants enrolled prior to AM4 will receive clesrovimab Dose 4 via IM injection and will be followed for up to 365 days.
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Drug: Clesrovimab
Single ascending doses of clesrovimab will be administered via IM injection.
Other Name: MK-1654 |
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Experimental: Panel D2: Pre-term clesrovimab Dose 4
Pre-term infants enrolled after AM4 will receive clesrovimab Dose 4 via IM injection and will be followed for up to 545 days.
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Drug: Clesrovimab
Single ascending doses of clesrovimab will be administered via IM injection.
Other Name: MK-1654 |
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Experimental: Panel E1: Full-term clesrovimab Dose 4
Full-term infants enrolled prior to AM4 will receive clesrovimab Dose 4 via IM injection and will be followed for up to 365 days.
|
Drug: Clesrovimab
Single ascending doses of clesrovimab will be administered via IM injection.
Other Name: MK-1654 |
|
Experimental: Panel E2: Full-term clesrovimab Dose 4
Full-term infants enrolled after AM4 will receive clesrovimab Dose 4 via IM injection and will be followed for up to 545 days.
|
Drug: Clesrovimab
Single ascending doses of clesrovimab will be administered via IM injection.
Other Name: MK-1654 |
|
Placebo Comparator: Placebo
Pre-term infants will receive placebo via IM injection.
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Drug: Placebo
Placebo (0.9% sodium chloride [NaCl]) will be administered via IM injection. |
Primary Outcome Measures :
- Percentage of participants experiencing a solicited injection site adverse event (AE) [ Time Frame: 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 will be monitored from Day 1 to Day 5.
- Percentage of participants experiencing a solicited systemic AE [ Time Frame: 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 will be monitored from Day 1 to Day 5.
- Percentage of participants experiencing a serious AE (SAE) [ Time Frame: Up to 545 days ]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 Outcome Measures :
- Area under the serum-concentration time curve from zero to infinity (AUC0-∞) [ Time Frame: 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.
- Maximum serum concentration (Cmax) of clesrovimab [ Time Frame: 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 [ Time Frame: At designated time points (up to 1 year post-dose) ]Tmax is the amount of time required to reach Cmax.
- Apparent terminal half-life (t1/2) of clesrovimab [ Time Frame: 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) [ Time Frame: Day 7 ]Serum concentration of clesrovimab will be measured on Day 7.
- Serum concentration of clesrovimab on Day 14 (C14days) [ Time Frame: Day 14 ]Serum concentration of clesrovimab will be measured on Day 14.
- Serum concentration of clesrovimab on Day 90 (C90days) [ Time Frame: Day 90 ]Serum concentration of clesrovimab will be measured on Day 90.
- Serum concentration of clesrovimab on Day 150 (C150days) [ Time Frame: Day 150 ]Serum concentration of clesrovimab will be measured on Day 150.
- Serum concentration of clesrovimab on Day 365 (C365days) [ Time Frame: Day 365 ]Serum concentration of clesrovimab will be measured on Day 365.
- Titer of ADAs to clesrovimab on Day 14: Panels A, B, C, D1 and E1 [ Time Frame: Day 14 ]Titers of ADAs to clesrovimab will be measured on Day 14.
- Titer of ADAs to clesrovimab on Day 90: Panels A, B, C, D1 and E1 [ Time Frame: Day 90 ]Titers of ADAs to clesrovimab will be measured on Day 90.
- Titer of ADAs to clesrovimab on Day 150: Panels A, B, C, D1, D2, E1, and E2 [ Time Frame: Day 150 ]Titers of ADAs to clesrovimab will be measured on Day 150.
- Titer of ADAs to clesrovimab on Day 365: Panels A, B, C, D1, D2, E1, and E2 [ Time Frame: Day 365 ]Titers of ADAs to clesrovimab will be measured on Day 365.
- Titer of ADAs to clesrovimab on Day 545: Panels D2 and E2 [ Time Frame: Day 545 ]Titers of ADAs to clesrovimab will be measured on Day 545.
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| Ages Eligible for Study: | 2 Weeks to 8 Months (Child) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | Yes |
Criteria
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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03524118
Locations
Show 34 study locations
Sponsors and Collaborators
Merck Sharp & Dohme LLC
Investigators
| Study Director: | Medical Director | Merck Sharp & Dohme LLC |
| Responsible Party: | Merck Sharp & Dohme LLC |
| ClinicalTrials.gov Identifier: | NCT03524118 |
| Other Study ID Numbers: |
1654-002 MK-1654-002 ( Other Identifier: Merck Protocol Number ) 2017-005062-21 ( EudraCT Number ) |
| First Posted: | May 14, 2018 Key Record Dates |
| Last Update Posted: | September 27, 2022 |
| Last Verified: | September 2022 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf |
| URL: | http://engagezone.msd.com/ds_documentation.php |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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Respiratory Tract Infections Infections Respiratory Tract Diseases |