Respiratory Syncytial Virus Clinical Trial
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
| Verified date | November 2023 |
| Source | Merck Sharp & Dohme LLC |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 183 |
| Est. completion date | September 14, 2022 |
| Est. primary completion date | September 14, 2022 |
| Accepts healthy volunteers | Accepts Healthy Volunteers |
| Gender | All |
| Age group | 2 Weeks to 8 Months |
| Eligibility | 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 |
| Country | Name | City | State |
|---|---|---|---|
| Chile | Centro de Investigacion Clinica Bradford Hill ( Site 0103) | Santiago | Region M. De Santiago |
| Chile | Facultad Medicina Universidad de Chile ( Site 0104) | Santiago | Region M. De Santiago |
| Chile | Hospital La Florida ( Site 0050) | Santiago | Region M. De Santiago |
| Chile | Hospital Padre Hurtado ( Site 0102) | Santiago | Region M. De Santiago |
| Colombia | Fundacion Universitaria de Ciencias de la Salud - Sociedad de Cirugia ( Site 0099) | Bogota | Distrito Capital De Bogota |
| Colombia | MedPlus Medicina Prepagada S.A. ( Site 0095) | Bogota | Distrito Capital De Bogota |
| Colombia | Fundacion Valle del Lili ( Site 0090) | Cali | Valle Del Cauca |
| Colombia | Centro de Atención e Investigación Médica SAS - CAIMED CHIA ( Site 0100) | Chia | Cundinamarca |
| Colombia | Fundacion Hospital San Vicente de Paul ( Site 0097) | Medellin | Antioquia |
| Colombia | Universidad Pontificia Bolivariana - Clinica Universitaria Bolivariana ( Site 0098) | Medellin | Antioquia |
| Korea, Republic of | Samsung Medical Center ( Site 0072) | Seoul | |
| Korea, Republic of | Seoul National University Hospital ( Site 0071) | Seoul | |
| Korea, Republic of | Severance Hospital Yonsei University Health System ( Site 0073) | Seoul | |
| South Africa | Tygerberg Hospital ( Site 0261) | Cape Town | Western Cape |
| South Africa | Chris Hani Baragwanath Academic Hospital ( Site 0262) | Johannesburg | Gauteng |
| Spain | Hospital Universitario La Paz ( Site 0242) | Madrid | |
| Spain | Hospital Clinico Universitario de Santiago ( Site 0241) | Santiago de Compostela | La Coruna |
| United States | Children's Hospital - Colorado ( Site 0067) | Aurora | Colorado |
| United States | Coastal Pediatric Research ( Site 0028) | Charleston | South Carolina |
| United States | Cincinnati Children's Hospital Medical Center ( Site 0031) | Cincinnati | Ohio |
| United States | Ohio Pediatric Research Association ( Site 0066) | Dayton | Ohio |
| United States | University of Texas Medical Branch at Galveston ( Site 0039) | Galveston | Texas |
| United States | Tribe Clinical Research, LLC ( Site 0082) | Greenville | South Carolina |
| United States | Next Phase Research Alliance, LLC ( Site 0075) | Homestead | Florida |
| United States | Kapiolani Medical Center for Women and Children ( Site 0027) | Honolulu | Hawaii |
| United States | Children's Mercy Hospital ( Site 0037) | Kansas City | Missouri |
| United States | Dartmouth-Hitchcock Medical Center ( Site 0032) | Lebanon | New Hampshire |
| United States | University of Wisconsin American Family Children's Hospital ( Site 0068) | Madison | Wisconsin |
| United States | Acevedo Clinical Research Associates ( Site 0025) | Miami | Florida |
| United States | WakeMed Health and Hospitals ( Site 0033) | Raleigh | North Carolina |
| United States | Tekton Research, Inc. ( Site 0026) | San Antonio | Texas |
| United States | SUNY Upstate Medical University Hospital ( Site 0029) | Syracuse | New York |
| United States | Multicare Institute For Research And Innovation ( Site 0035) | Tacoma | Washington |
| United States | Cotton-O'Neil Clinical Research Center PediatricCare ( Site 0081) | Topeka | Kansas |
| Lead Sponsor | Collaborator |
|---|---|
| Merck Sharp & Dohme LLC |
United States, Chile, Colombia, Korea, Republic of, South Africa, Spain,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| 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. | Up to Day 5 | |
| 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. | Up to Day 5 | |
| 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. | Up to Day 545 | |
| Secondary | Area Under the Serum-Concentration Time Curve From Zero to Infinity (AUC0-8) | AUC0-8 is a measure of the extrapolated mean concentration in serum from dosing to infinity. | At designated time points (up to 1 year post-dose) | |
| Secondary | Maximum Serum Concentration (Cmax) of Clesrovimab | Cmax is the highest observed serum drug concentration. | At designated time points (up to 1 year post-dose) | |
| Secondary | Time to Maximum Serum Concentration (Tmax) of Clesrovimab | Tmax is the time taken to reach the maximum observed plasma (Cmax) concentration of Clesrovimab. | At designated time points (up to 1 year post-dose) | |
| Secondary | Apparent Terminal Half-life (t1/2) of Clesrovimab | t1/2 is the time required for 50% of drug to be cleared from serum. | At designated time points (up to 1 year post-dose) | |
| Secondary | Serum Concentration of Clesrovimab on Day 7 (C7days) | Serum concentration of clesrovimab was measured on Day 7. | Day 7 | |
| Secondary | Serum Concentration of Clesrovimab on Day 14 (C14days) | Serum concentration of clesrovimab was measured on Day 14. | Day 14 | |
| Secondary | Serum Concentration of Clesrovimab on Day 90 (C90days) | Serum concentration of clesrovimab was measured on Day 90. | Day 90 | |
| Secondary | Serum Concentration of Clesrovimab on Day 150 (C150days) | Serum concentration of clesrovimab was measured on Day 150. | Day 150 | |
| Secondary | Serum Concentration of Clesrovimab on Day 365 (C365days) | Serum concentration of clesrovimab was measured on Day 365. | Day 365 | |
| 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. | Days 14, 90, 150, 365 and 545 |
| Status | Clinical Trial | Phase | |
|---|---|---|---|
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