Prevention of Respiratory syncytial virus (RSV) infection in infants and children at increased risk for severe RSV disease MedDRA version: 21.1 Level: LLT Classification code 10066742 Term: Respiratory syncytial virus infection prophylaxis System Organ Class: 100000004865
Conditions
Interventions
Product Code: MK-1654
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Not available
Current Sponsor code: MK-1654
Other descriptive name: MK-1654 (SUB221140)
Concentration unit: mg/ml
Sponsors
Merck Sharp & Dohme LLC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Recommended to receive palivizumab in accordance with national or local guidelines or professional society recommendations, and meets 1 or more of the following criteria: a) Early or Moderate Pre-term Group (excluding participants with CLD or hemodynamically significant CHD): =35 weeks, 0 days gestational age. b) CLD/CHD Group: - CLD Participants: have CLD of prematurity (also known as bronchopulmonary dysplasia), as defined by: ? American Academy of Pediatrics [American Academy of Pediatrics Committee on Infectious Diseases 2014]: =32 weeks, 0 days gestational age and require medical intervention/management for at least 28 days after birth, or ? Other national or local guidelines or professional society recommendations. - CHD Participants: have hemodynamically significant CHD, as defined by: ? American Academy of Pediatrics [American Academy of Pediatrics Committee on Infectious Diseases 2014]: Uncorrected or palliated cyanotic or acyanotic disease associated with documented pulmonary hypertension or a requirement for daily medication to manage congestive heart failure, or as diagnosed by a pediatric cardiologist ? other national or local guidelines or professional society recommendations. 2. Is available to complete the follow-up period: - Up to 575 days (180 days after RSV Season 2 dose) for participants eligible for RSV Season 2 dose of MK-1654, or - Approximately 365 days after the RSV Season 1 Dose 1 for all other participants. 3. Is male or female and has a chronological age from birth up to 1 year and is entering their first RSV season at the time informed consent is provided. 4. The participant’s legally acceptable representative provides documented informed consent for the study. The participant’s legally acceptable representative may also provide documented consent for future biomedical research. However, the participant may participate in the main study without participating in future biomedical research. For Participation in RSV Season 2: 5. Participants enrolled in the CLD/CHD group as defined in Inclusion Criteria #1b. Participants with CHD are required to meet the following additional criteria: - Have hemodynamically significant CHD at the beginning of RSV Season 2, or - If the participant has had surgically repaired hemodynamically significant CHD that did not include ECMO or cardiopulmonary bypass: ? Continues to require medications to manage CHD, or ? Any additional medical intervention related to their CHD 6. Participants enrolled in the Early or Moderate Pre-term Group as defined in Inclusion Criteria #1a, with the following: - Neuromuscular disease or congenital pulmonary anomaly that impairs the ability to clear secretions from the upper airway because of ineffective cough - Down Syndrome (trisomy of chromosome 21) - Cystic fibrosis with nutritional compromise (eg, weight =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Requires mechanical ventilation at time of enrollment. 2. Has a life expectancy <6 months. 3. Has known hepatic or renal dysfunction, or chronic seizure disorder. 4. Is hospitalized at the time of randomization unless discharge is expected within 7 days after randomization. 5. Has severe immunodeficiency or is severely immunocompromised, including but not limited to: - AIDS (CD4 percentage <15%, or history of AIDS-Defining Condition), - leukemia, myeloproliferative disorder, or other malignancy and receiving or expected to receive chemotherapy during the study, - status post solid-organ or bone marrow transplantation and on a systemic immunosuppressive regimen, OR - severe combined immunodeficiency. 6. Has known hypersensitivity to any component of MK-1654 or palivizumab. 7. Has received other investigational agents at any time before study entry. 8. Is anticipated to have either of the following within 60 days after randomization resulting in: 1) surgical correction hemodynamically insignificant CHD. 2) cardiac surgical procedure that will require cardiopulmonary bypass. 9. Requires ECMO or continuous positive airway pressure at the time of enrollment or anticipated within 60 days after randomization. 10. Has an anticipated or planned cardiac transplantation to occur during the course of this study. 11. Has a bleeding disorder contraindicating intramuscular administration. 12. 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. 13. Has symptoms of LRI within 7 days predose. 14. Has received any vaccine or mAb for the prevention of RSV, including receipt of maternal RSV vaccination during the mother’s pregnancy. 15. 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 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. 16. Has enrolled previously in the current study and been discontinued. 17. Has a parent/legal guardian/legally acceptable representative who is unlikely to adhere to study procedures, keep appointments, or is planning to relocate during the study. 18. Has any other reason that in the opinion of the investigator may interfere with the evaluation required by the study. 19. Is or has an immediate family member (eg, spouse, parent/legal guardian, sibling, or child) who is investigational site or Sponsor staff directly involved with this study. For Participation in RSV Season 2: 20. Has a life expectancy <6 months. 21. Has known hepatic or renal dysfunction, or chronic seizure disorder. 22. Has severe immunodeficiency or is severely immunocompromised, including but not limited to: - AIDS (CD4 percentage <15%, or history of AIDS-Defining Condition), - leukemia, myeloproliferative disorder, or other malignancy and receiving or expected to receive chemotherapy during the study, - status post solid-organ or bone marrow transplantation and on a systemic immunosuppressive regimen, OR - severe combined immunodeficiency. 23. Had 1) ECMO or 2) surgical intervention during the RSV season for CHD and required cardiopulmonary bypass during the procedure in RSV Season 1. 24. Has known hypersensitivity to any component of MK-1654. 25. Has bleeding disorder contraindicating intramuscular administration.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the safety and tolerability of MK-1654 compared to palivizumab in RSV Season 1 as assessed by the proportion of participants experiencing AEs.;Secondary Objective: 1. To estimate the efficacy of MK-1654 compared to palivizumab as assessed by the incidence of RSV-associated MALRI (outpatient and inpatient) from Days 1 through 150 post Dose 1 in RSV Season 1. 2. To estimate the incidence of RSV-associated hospitalizations from Days 1 through 150 post Dose 1 in RSV Season 1 in the MK-1654 and palivizumab groups. 3. To describe the serum PK concentration of MK-1654 at Days 7, 150, and 240 after the dose of MK-1654 in RSV Season 1. 4. To describe the safety of MK-1654 administered in RSV Season 2 as assessed by the proportion of participants experiencing AEs. 5. To describe the serum PK concentration of MK-1654 at Days 7 and 150 postdose in RSV Season 2. ;Primary end point(s): 1. Percentage of participants with solicited injection-site Adverse Events (AEs) in respiratory syncytial virus (RSV) Season 1 2. Percentage of participants with solicited daily body temperature with fever in RSV Season 1 3. Percentage of participants with solicited systemic AEs in RSV Season 1 4. Percentage of participants with anaphylaxis/hypersensitivity AEs of special interest (AESI) in RSV Season 1 5. Percentage of participants with rash AESI in RSV Season 1 6. Percentage of participants with non-serious AEs in RSV Season 1 7. Percentage of participants with serious AEs (SAEs) through the duration of participation in RSV Season 1;Timepoint(s) of evaluation of this end point: 1. Days 1 through 5 after each dose in RSV Season 1 2. Days 1 through 5 after each dose in RSV Season 1 3. Days 1 through 5 after each dose in RSV Season 1 4. Days 1 through 28 after Dose 1 and Days 1 through 14 after Dose 2 in RSV Season 1 5. Days 1 through 28 after Dose 1 and Days 1 through 14 after Dose 2 in RSV Season 1 6. Days 1 through 28 after Dose 1 and 14 days after each dose in RSV Se | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Percentage of participants with RSV-associated medically attended lower respiratory infection (MALRI) in RSV Season 1 2. Percentage of participants with RSV-associated hospitalization in RSV Season 1 3. Percentage of participants with solicited injection-site AEs in RSV Season 2 4. Percentage of participants with solicited daily body temperature with fever in RSV Season 2 5. Percentage of participants with solicited systemic AEs in RSV Season 2 6. Percentage of participants with anaphylaxis/hypersensitivity AESI in RSV Season 2 7. Percentage of participants with rash AESI in RSV Season 2 8. Percentage of participants with non-serious AEs in RSV Season 2 9. Percentage of participants with SAEs through 180 days postdose in RSV Season 2 10. Serum concentration of MK-1654 after dose of MK-1654 in RSV Season 1 11. Serum concentration of MK-1654 after dose of MK-1654 in RSV Season 2;Timepoint(s) of evaluation of this end point: 1. Days 1 through 150 post Dose 1 in RSV Season 1 2. Days 1 through 150 post Dose 1 in RSV Season 1 3. Days 1 through 5 postdose in RSV Season 2 4. Days 1 through 5 postdose in RSV Season 2 5. Days 1 through 5 postdose in RSV Season 2 6. Days 1 through 42 postdose in RSV Season 2 7. Days 1 through 42 postdose in RSV Season 2 8. Days 1 through 42 postdose in RSV Season 2 9. Days 1 through 180 postdose in RSV Season 2 10. Days 7, 150, and 240 after dose of MK-1654 in RSV Season 1 11. Days 7 and 150 after dose of MK-1654 in RSV Season 2 | — |
Countries
Australia, Canada, Chile, Colombia, Czechia, Czech Republic, Finland, France, Germany, Greece, Hungary, Italy, Japan, Malaysia, Mexico, New Zealand, Norway, Peru, Puerto Rico, Russian Federation, Singapore, South Africa, Spain, Taiwan, Thailand, Turkey, United Kingdom, United States
Contacts
Public ContactGCTO
Merck Sharp & Dohme LLC
Outcome results
None listed