Study to Evaluate Sotatercept (MK-7962) in Children With Pulmonary Arterial Hypertension (PAH) (MK-7962-008)
- Registration Number
- NCT05587712
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
The primary objectives of the study are to evaluate the safety and tolerability, and pharmacokinetics (PK) of sotatercept over 24 weeks of treatment in children ≥1 to \<18 years of age with PAH World Health Organization (WHO) Group 1 on standard of care (SoC). There is no formal hypothesis.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 42
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Children ≥1 to <18 years old Sotatercept Participants will receive a subcutaneous (SC) injection every 3 weeks (Q3W) of 0.3 mg/kg. Dosage may be adjusted based on protocol-specific guidelines.
- Primary Outcome Measures
Name Time Method Laboratory Parameter (Hematology): Concentration of Hemoglobin Up to 24 weeks Hematological parameters will be investigated in blood samples from participants by means of clinical laboratory assays and evaluated by the investigator. The concentration of hemoglobin will be presented.
Laboratory Parameter (Hematology): Hematocrit Up to 24 weeks Hematological parameters will be investigated in blood samples from participants by means of clinical laboratory assays and evaluated by the investigator. The hematocrit will be presented.
Laboratory Parameter (Hematology): Red Blood Cell (RBC) Count Up to 24 weeks Hematological parameters will be investigated in blood samples from participants by means of clinical laboratory assays and evaluated by the investigator. The RBC count will be presented.
Serum Trough Concentration (Ctrough) of Sotatercept Predose Day 1, Day 21, Day 42, Day 63, Day 84, Day105, Day 126, Day 147, Day 168, Day 189. Postdose Day 7, Day 14, Day 64, Day 69 and Day 76 Ctrough was the lowest concentration of Sotatercept in serum just before the next dose. Blood samples will be collected at multiple time points to estimate the Ctrough of Sotatercept.
Percentage of Participants Who Experience at Least 1 Adverse Event (AE) Up to 24 weeks An AE is any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. The percentage of participants with 1 or more AEs will be assessed.
Area Under the Curve at Steady State (AUCss) of Sotatercept Predose Day 1, Day 21, Day 42, Day 63, Day 84, Day105, Day 126, Day 147, Day 168, Day 189. Postdose Day 7, Day 14, Day 64, Day 69 and Day 76 Blood samples will be collected at multiple time points to estimate the AUCss of Sotatercept.
Area Under the Curve from 0 to 3 weeks (AUC0-3 weeks) of Sotatercept Predose Day 1, Day 7, Day 14, and Predose Day 21 Blood samples will be collected at Predose Day 1, Day 7, Day 14, and Predose Day 21 to estimate the AUC0-3 weeks of Sotatercept.
Percentage of Participants Who Discontinue Study Drug Due to an AE Up to 24 weeks An AE is any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. The percentage of participants who discontinued the study drug due to an AE regardless of study completion status will be assessed.
Laboratory Parameter (Hematology): Reticulocyte Count Up to 24 weeks Hematological parameters will be investigated in blood samples from participants by means of clinical laboratory assays and evaluated by the investigator. The reticulocyte count will be presented.
Laboratory Parameter (Hematology): Platelet Count Up to 24 weeks Hematological parameters will be investigated in blood samples from participants by means of clinical laboratory assays and evaluated by the investigator. The platelet count will be presented.
Blood Pressure (BP) Up to 24 weeks BP will be assessed while the participant was seated after a period of rest in a quiet setting with no distractions (eg, television and cell phones).
Titer of Anti-drug Antibody (ADA) to Sotatercept Up to 24 weeks ADA to Sotatercept will be assessed.
- Secondary Outcome Measures
Name Time Method Mean Change from Baseline in Tricuspid Annular Plane Systolic Excursion (TAPSE) Baseline and Week 24 A two-dimensional echocardiogram (ECHO) will be performed with the results interpreted by a blinded independent central review (BICR) at baseline and after 24 weeks of treatment. The change from baseline in TAPSE will be reported.
Mean Change from Baseline in Pulmonary Artery Systolic Pressure (PASP) Baseline and Week 24 A two-dimensional ECHO will be performed with the results interpreted by a BICR at baseline and after 24 weeks of treatment. The change from baseline in PASP will be reported.
Mean Change from Baseline in 6-Minute Walk Distance (6MWD) (Cohorts 1 and 2) Baseline and Week 24 6MWD will be assessed using the 6-minute walk test (6MWT).
Mean Change from Baseline in Eccentricity Index Baseline and Week 24 A two-dimensional ECHO will be performed with the results interpreted by a BICR at baseline and after 24 weeks of treatment. The change from baseline in eccentricity index will be reported.
Mean Change from Baseline on Cardiac Output (Cohorts 1 and 2) Baseline and Week 24 Cardiac magnetic imaging (MRI) will be performed with the results interpreted by a BICR at baseline and after 24 weeks of treatment. The change from baseline in cardiac output will be reported.
Mean Change from Baseline in Right Ventricular (RV) Function (Cohorts 1 and 2) Baseline and Week 24 Cardiac magnetic imaging (MRI) will be performed with the results interpreted by a BICR at baseline and after 24 weeks of treatment. The change from baseline in eccentricity index will be reported.
Mean Change from Baseline in Pulmonary Arterial Pressure (PAP) (Cohorts 1 and 2) Baseline and Week 24 Cardiac magnetic imaging (MRI) will be performed with the results interpreted by a BICR at baseline and after 24 weeks of treatment. The change from baseline in PAP will be reported.
Mean Change from Baseline in Pediatric Quality of Life (PedsQL) Generic Score Baseline and Week 24 PedsQL Measurement Model is a modular approach to measuring health-related quality of life in healthy children and adolescents and those with acute and chronic health conditions. The change from baseline in the PedsQL generic core scale will be reported.
Mean Change from Baseline in N-terminal Prohormone B-type Natriuretic Peptide (NT-proBNP) Baseline and Week 24 The change from baseline in plasma NT-proBNP levels will be reported.
Percentage of Participants Who Either Improved or Maintained Their World Health Organization Functional Class (WHO FC) Baseline and Week 24 The severity of an individual's PAH symptoms will be graded using the WHO FC system. WHO functional classification for PAH range from Class I (no limitation in physical activity, no dyspnea with normal activity), Class II (slight limitation of physical activity), Class III (marked limitation of physical activity) and Class IV (cannot perform a physical activity without any symptoms, dyspnea at rest). The change from baseline in WHO FC will be classified into "Improved", "No change" and "Worsened". Improvement = reduction in FC, worsened = increase in FC and no change = no change in FC.
Mean Change from Baseline in Right Ventricular Fractional Area Change (RVFAC) Baseline and Week 24 A two-dimensional ECHO will be performed with the results interpreted by a BICR at baseline and after 24 weeks of treatment. The change from baseline in RVFAC will be reported.
Trial Locations
- Locations (35)
The Regents of the University of California - Los Angeles (UCLA Pediatrics) ( Site 1606)
🇺🇸Los Angeles, California, United States
Stanford University School of Medicine ( Site 1603)
🇺🇸Palo Alto, California, United States
UCSF Benioff Children's Hospital San Francisco ( Site 1611)
🇺🇸San Francisco, California, United States
Children's Hospital Colorado ( Site 1609)
🇺🇸Aurora, Colorado, United States
Children's National Medical Center ( Site 1600)
🇺🇸Washington, District of Columbia, United States
Cincinnati Children's Hospital Medical Center ( Site 1602)
🇺🇸Cincinnati, Ohio, United States
Children's Hospital of Philadelphia (CHOP) ( Site 1608)
🇺🇸Philadelphia, Pennsylvania, United States
Monroe Carell Jr. Children's Hospital ( Site 1601)
🇺🇸Nashville, Tennessee, United States
Seattle Children's Hospital ( Site 1605)
🇺🇸Seattle, Washington, United States
Children's Wisconsin ( Site 1610)
🇺🇸Milwaukee, Wisconsin, United States
The Children's Hospital at Westmead ( Site 0001)
🇦🇺Westmead, New South Wales, Australia
Clinica Somer-Unidad de Investigacion y Docencia ( Site 0205)
🇨🇴Rionegro, Antioquia, Colombia
Fundación Valle del Lili ( Site 0200)
🇨🇴Cali, Valle Del Cauca, Colombia
Clínica Imbanaco S.A.S ( Site 0203)
🇨🇴Cali, Valle Del Cauca, Colombia
CHU de Toulouse - Hôpital des Enfants ( Site 0302)
🇫🇷Toulouse, Haute-Garonne, France
Assistance Publique Hôpitaux de Marseille - Hôpital de la Timone ( Site 0303)
🇫🇷Marseille, Provence-Alpes-Cote-d Azur, France
Hôpital Universitaire Necker Enfants Malades ( Site 0300)
🇫🇷Paris, France
Universitaetsklinikum Heidelberg ( Site 0401)
🇩🇪Heidelberg, Baden-Wurttemberg, Germany
Klinikum der Universität München Großhadern ( Site 0404)
🇩🇪München, Bayern, Germany
Medizinische Hochschule Hannover ( Site 0405)
🇩🇪Hannover, Niedersachsen, Germany
Schneider Children's Medical Center ( Site 0603)
🇮🇱Petah-Tikva, Israel
Sheba Medical Center ( Site 0601)
🇮🇱Ramat Gan, Israel
University Medical Center Groningen ( Site 0900)
🇳🇱Groningen, Netherlands
Centrum Zdrowia Dziecka w Warszawie-Klinika Kardiologii ( Site 1103)
🇵🇱Warszawa, Mazowieckie, Poland
Uniwersyteckie Centrum Kliniczne-Klinika Kardiologii Dziecięcej i Wad Wrodzonych Serca ( Site 1102)
🇵🇱Gdańsk, Pomorskie, Poland
Wits Clinical Research-Wits Clinical Research Bara ( Site 1201)
🇿🇦Johannesburg, Soweto, Gauteng, South Africa
Hospital Universitario Ramón y Cajal ( Site 1300)
🇪🇸Madrid, Madrid, Comunidad De, Spain
Hospital Universitari i Politecnic La Fe ( Site 1303)
🇪🇸València, Valencia, Spain
Hospital Universitari Vall d'Hebron ( Site 1302)
🇪🇸Barcelona, Spain
HOSPITAL GENERAL UNIVERSITARIO GREGORIO MARAÑON ( Site 1301)
🇪🇸Madrid, Spain
Hacettepe Universite Hastaneleri ( Site 1400)
🇹🇷Ankara, Turkey
Gazi University Health Research and Application Center Gazi -Çocuk Sağlığı ve Hastalıkları Anabilim ( Site 1402)
🇹🇷Ankara, Turkey
Ankara Bilkent Şehir Hastanesi. ( Site 1403)
🇹🇷Ankara, Turkey
Mehmet Akif Ersoy Research and Training Hospital ( Site 1404)
🇹🇷Istanbul, Turkey
Great Ormond Street Hospital For Children NHS Foundation Trust ( Site 1500)
🇬🇧London, London, City Of, United Kingdom