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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
42
SC injection every 3 weeks (Q3W) of 0.3 mg/kg. Dosage may be adjusted based on protocol-specific guidelines.
Serum Trough Concentration (Ctrough) of Sotatercept
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.
Time frame: 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
Area Under the Curve at Steady State (AUCss) of Sotatercept
Blood samples will be collected at multiple time points to estimate the AUCss of Sotatercept.
Time frame: 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
Area Under the Curve from 0 to 3 weeks (AUC0-3 weeks) of Sotatercept
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.
Time frame: Predose Day 1, Day 7, Day 14, and Predose Day 21
Percentage of Participants Who Experience at Least 1 Adverse Event (AE)
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.
Time frame: Up to 24 weeks
Percentage of Participants Who Discontinue Study Drug Due to an AE
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.
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The Regents of the University of California - Los Angeles (UCLA Pediatrics) ( Site 1606)
Los Angeles, California, United States
RECRUITINGStanford University School of Medicine ( Site 1603)
Palo Alto, California, United States
RECRUITINGUCSF Benioff Children's Hospital San Francisco ( Site 1611)
San Francisco, California, United States
RECRUITINGChildren's Hospital Colorado ( Site 1609)
Aurora, Colorado, United States
RECRUITINGChildren's National Medical Center ( Site 1600)
Washington D.C., District of Columbia, United States
RECRUITINGCincinnati Children's Hospital Medical Center ( Site 1602)
Cincinnati, Ohio, United States
RECRUITINGChildren's Hospital of Philadelphia (CHOP) ( Site 1608)
Philadelphia, Pennsylvania, United States
RECRUITINGMonroe Carell Jr. Children's Hospital ( Site 1601)
Nashville, Tennessee, United States
COMPLETEDSeattle Children's Hospital ( Site 1605)
Seattle, Washington, United States
RECRUITINGChildren's Wisconsin ( Site 1610)
Milwaukee, Wisconsin, United States
RECRUITING...and 25 more locations
Time frame: Up to 24 weeks
Laboratory Parameter (Hematology): Concentration of Hemoglobin
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.
Time frame: Up to 24 weeks
Laboratory Parameter (Hematology): Hematocrit
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.
Time frame: Up to 24 weeks
Laboratory Parameter (Hematology): Red Blood Cell (RBC) Count
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.
Time frame: Up to 24 weeks
Laboratory Parameter (Hematology): Reticulocyte Count
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.
Time frame: Up to 24 weeks
Laboratory Parameter (Hematology): Platelet Count
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.
Time frame: Up to 24 weeks
Blood Pressure (BP)
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).
Time frame: Up to 24 weeks
Titer of Anti-drug Antibody (ADA) to Sotatercept
ADA to Sotatercept will be assessed.
Time frame: Up to 24 weeks
Mean Change from Baseline in 6-Minute Walk Distance (6MWD) (Cohorts 1 and 2)
6MWD will be assessed using the 6-minute walk test (6MWT).
Time frame: Baseline and Week 24
Mean Change from Baseline in Tricuspid Annular Plane Systolic Excursion (TAPSE)
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.
Time frame: Baseline and Week 24
Mean Change from Baseline in Pulmonary Artery Systolic Pressure (PASP)
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.
Time frame: Baseline and Week 24
Mean Change from Baseline in Right Ventricular Fractional Area Change (RVFAC)
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.
Time frame: Baseline and Week 24
Mean Change from Baseline in Eccentricity Index
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.
Time frame: Baseline and Week 24
Mean Change from Baseline in Right Ventricular (RV) Function (Cohorts 1 and 2)
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.
Time frame: Baseline and Week 24
Mean Change from Baseline on Cardiac Output (Cohorts 1 and 2)
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.
Time frame: Baseline and Week 24
Mean Change from Baseline in Pulmonary Arterial Pressure (PAP) (Cohorts 1 and 2)
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.
Time frame: Baseline and Week 24
Mean Change from Baseline in Pediatric Quality of Life (PedsQL) Generic Score
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.
Time frame: Baseline and Week 24
Mean Change from Baseline in N-terminal Prohormone B-type Natriuretic Peptide (NT-proBNP)
The change from baseline in plasma NT-proBNP levels will be reported.
Time frame: Baseline and Week 24
Percentage of Participants Who Either Improved or Maintained Their World Health Organization Functional Class (WHO FC)
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.
Time frame: Baseline and Week 24