Study to Evaluate Sotatercept (MK-7962) in Children With Pulmonary Arterial Hypertension (PAH) (MK-7962-008) (MOONBEAM)

A Phase 2 Open-label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Sotatercept (MK-7962) in Children From 1 to Less Than 18 Years of Age With PAH on Standard of Care

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 Overview

• Status: Recruiting
• Conditions: Pulmonary Arterial Hypertension
• Intervention / Treatment: Drug: Sotatercept

• Study Type: Interventional
• Enrollment (Estimated): 42
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Toll Free Number; Phone Number: 1-888-577-8839; Email: Trialsites@merck.com

Study Locations

• Australia
  • New South Wales
    • Westmead, New South Wales, Australia, 2145
      • Recruiting
      • The Children's Hospital at Westmead ( Site 0001)
      • Contact: Study Coordinator; Phone Number: 0298452345
• Colombia
  • Valle Del Cauca
    • Cali, Valle Del Cauca, Colombia, 760042
      • Recruiting
      • Clínica Imbanaco S.A.S ( Site 0203)
      • Contact: Study Coordinator; Phone Number: +57 301 6613144
    • Cali, Valle Del Cauca, Colombia, 760032
      • Recruiting
      • Fundación Valle del Lili ( Site 0200)
      • Contact: Study Coordinator; Phone Number: 3165212877
• France
  • Paris, France, 75015
    • Recruiting
    • Hôpital Universitaire Necker Enfants Malades ( Site 0300)
    • Contact: Study Coordinator; Phone Number: 33679166652
  • Haute-Garonne
    • Toulouse, Haute-Garonne, France, 31059
      • Recruiting
      • CHU de Toulouse - Hôpital des Enfants ( Site 0302)
      • Contact: Study Coordinator; Phone Number: 05345558596
  • Provence-Alpes-Cote-d Azur
    • Marseille, Provence-Alpes-Cote-d Azur, France, 13005
      • Recruiting
      • Assistance Publique Hôpitaux de Marseille - Hôpital de la Timone ( Site 0303)
      • Contact: Study Coordinator; Phone Number: +334 91 38 67 50
• Germany
  • Baden-Wurttemberg
    • Heidelberg, Baden-Wurttemberg, Germany, 69120
      • Recruiting
      • Universitaetsklinikum Heidelberg ( Site 0401)
      • Contact: Study Coordinator; Phone Number: +496221564606
  • Bayern
    • München, Bayern, Germany, 81337
      • Recruiting
      • Klinikum der Universität München Großhadern ( Site 0404)
      • Contact: Study Coordinator; Phone Number: 004989440073941
  • Niedersachsen
    • Hannover, Niedersachsen, Germany, 30625
      • Recruiting
      • Medizinische Hochschule Hannover ( Site 0405)
      • Contact: Study Coordinator; Phone Number: 0049 511 532 9041
• Israel
  • Petah-Tikva, Israel, 49202
    • Recruiting
    • Schneider Children's Medical Center ( Site 0603)
    • Contact: Study Coordinator; Phone Number: 050-4057131
  • Ramat Gan, Israel, 5265601
    • Recruiting
    • Sheba Medical Center ( Site 0601)
    • Contact: Study Coordinator; Phone Number: 972 0526667332
• Netherlands
  • Groningen, Netherlands, 9700RB
    • Recruiting
    • University Medical Center Groningen ( Site 0900)
    • Contact: Study Coordinator; Phone Number: 31505612800
• Poland
  • Mazowieckie
    • Warszawa, Mazowieckie, Poland, 04-730
      • Recruiting
      • Centrum Zdrowia Dziecka w Warszawie-Klinika Kardiologii ( Site 1103)
      • Contact: Study Coordinator; Phone Number: +48228157370
  • Pomorskie
    • Gdańsk, Pomorskie, Poland, 80-952
      • Recruiting
      • Uniwersyteckie Centrum Kliniczne-Klinika Kardiologii Dziecięcej i Wad Wrodzonych Serca ( Site 1102)
      • Contact: Study Coordinator; Phone Number: +48695687587
• Spain
  • Barcelona, Spain, 08035
    • Recruiting
    • Hospital Universitari Vall d'Hebron ( Site 1302)
    • Contact: Study Coordinator; Phone Number: 626774330
  • Madrid, Spain, 28007
    • Recruiting
    • HOSPITAL GENERAL UNIVERSITARIO GREGORIO MARAÑON ( Site 1301)
    • Contact: Study Coordinator; Phone Number: +34 915 86 80 00
  • Madrid, Comunidad De
    • Madrid, Madrid, Comunidad De, Spain, 28034
      • Recruiting
      • Hospital Universitario Ramón y Cajal ( Site 1300)
      • Contact: Study Coordinator; Phone Number: +34 913 36 80 00
  • Valencia
    • València, Valencia, Spain, 46026
      • Recruiting
      • Hospital Universitari i Politecnic La Fe ( Site 1303)
      • Contact: Study Coordinator; Phone Number: 699 449 273
• Turkey
  • Ankara, Turkey, 06100
    • Recruiting
    • Hacettepe Universite Hastaneleri ( Site 1400)
    • Contact: Study Coordinator; Phone Number: 05325503041
  • Ankara, Turkey, 06560
    • Recruiting
    • Gazi University Health Research and Application Center Gazi -Çocuk Sağlığı ve Hastalıkları Anabilim
    • Contact: Study Coordinator; Phone Number: 05553684926
  • Ankara, Turkey, 06800
    • Recruiting
    • Ankara Bilkent Şehir Hastanesi. ( Site 1403)
    • Contact: Study Coordinator; Phone Number: +905053166839
  • Istanbul, Turkey, 34303
    • Recruiting
    • Mehmet Akif Ersoy Research and Training Hospital ( Site 1404)
    • Contact: Study Coordinator; Phone Number: +905422560601
• United Kingdom
  • London, City Of
    • London, London, City Of, United Kingdom, WC1N 3JH
      • Recruiting
      • Great Ormond Street Hospital For Children NHS Foundation Trust ( Site 1500)
      • Contact: Study Coordinator; Phone Number: 02074059200
• United States
  • California
    • Los Angeles, California, United States, 90095
      • Recruiting
      • The Regents of the University of California - Los Angeles (UCLA Pediatrics) ( Site 1606)
      • Contact: Study Coordinator; Phone Number: 310-505-0088
    • Palo Alto, California, United States, 94304
      • Recruiting
      • Stanford University School of Medicine ( Site 1603)
      • Contact: Study Coordinator; Phone Number: 267-398-3637
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • Children's Hospital Colorado ( Site 1609)
      • Contact: Study Coordinator; Phone Number: 303-921-4811
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Recruiting
      • Children's National Medical Center ( Site 1600)
      • Contact: Study Coordinator; Phone Number: 202-476-2130
  • Ohio
    • Cincinnati, Ohio, United States, 45245
      • Recruiting
      • Cincinnati Children's Hospital Medical Center ( Site 1602)
      • Contact: Study Coordinator; Phone Number: 513-636-7072
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Recruiting
      • Monroe Carell Jr. Children's Hospital ( Site 1601)
      • Contact: Study Coordinator; Phone Number: 615-875-6901
  • Washington
    • Seattle, Washington, United States, 98105
      • Recruiting
      • Seattle Children's Hospital ( Site 1605)
      • Contact: Study Coordinator; Phone Number: 206-877-2219

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

• Documented, historic diagnostic right heart catheterization (RHC) any time before Screening confirming the diagnosis of PAH WHO Group 1 in any of the following subtypes:
• Idiopathic pulmonary arterial hypertension (IPAH)
• Heritable PAH
• Drug/toxin-induced PAH
• PAH associated with connective tissue disease
• PAH-congenital heart disease (CHD) with shunt closure >6 months before Screening and subsequently confirmed by RHC before Screening
• PAH with coincidental shunt.
• Must be on a stable dose(s) of background PAH therapy (phosphdiesterase-5 (PDE5) inhibitors, endothelin receptor antagonists (ERAs), soluble guanylate cyclase stimulators (sGCS), or prostanoids [including subcutaneous and intravenous])
• If male, agree to the following during the intervention period and for at least 16 weeks (112 days) after the last dose of study intervention:
• Abstains from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agrees to remain abstinent or
• Uses contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause, documented from the site personnel's review of the participant's medical records, medical examination, or medical history interview) as detailed below:
• Uses a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a woman of childbearing potential (WOCBP) who is not currently pregnant Note: Men with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal intercourse or use a male condom during each episode of penile-vaginal penetration.
• If female, must be either not a WOCBP or use a contraceptive method that is highly effective or be abstinent from heterosexual intercourse during the intervention period and for at least 16 weeks (112 days) after the last dose of study intervention
• If male, agrees to refrain from donating blood or sperm for the duration of the study and for 16 weeks (112 days) after the last dose of study intervention
• If female, agrees to refrain from donating blood, eggs, or ovum for the duration of the study and for at least 16 weeks (112 days) after the last dose of study intervention

Exclusion Criteria

• History of left-sided heart disease, including valvular disease (eg, moderate or greater mitral or aortic regurgitation or stenosis), left ventricular outflow tract obstruction, and/or left heart failure (eg, restrictive or dilated cardiomyopathy)
• Severe (as based on the opinion of the investigator) congenital or developmental abnormalities of the lung, thorax, and/or diaphragm
• History of Eisenmenger syndrome, Potts shunt, or atrial septostomy
• Unrepaired or residual cardiac shunt
• Diagnosis of pulmonary veno-occlusive diseases, pulmonary capillary hemangiomatosis, or overt signs of capillary and/or venous involvement
• PAH associated with portal hypertension
• Known visceral (lung, liver, or brain) arteriovenous malformation(s)
• History of full or partial pneumonectomy
• Untreated more than mild obstructive sleep apnea
• History of known pericardial constriction
• Family history of sudden cardiac death or long QT syndrome
• Any current or prior history of symptomatic coronary disease (myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft surgery, or cardiac anginal chest pain) within 6 months before Screening
• Cerebrovascular accident within 3 months before Screening
• Prior exposure to sotatercept or luspatercept or has had an allergic reaction to any of their excipients

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Children ≥1 to <18 years old; 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.	Drug: Sotatercept; SC injection every 3 weeks (Q3W) of 0.3 mg/kg. Dosage may be adjusted based on protocol-specific guidelines.; Other Names: MK-7962

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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).	Up to 24 weeks
Titer of Anti-drug Antibody (ADA) to Sotatercept	ADA to Sotatercept will be assessed.	Up to 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	Baseline and Week 24

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

Helpful Links

• Merck Clinical Trials Information
• Plain Language Summary

Study record dates

Study Major Dates

• Study Start (Actual): January 19, 2023
• Primary Completion (Estimated): September 21, 2028
• Study Completion (Estimated): September 21, 2028

Study Registration Dates

• First Submitted: October 17, 2022
• First Submitted That Met QC Criteria: October 17, 2022
• First Posted (Actual): October 20, 2022

Study Record Updates

• Last Update Posted (Actual): April 8, 2024
• Last Update Submitted That Met QC Criteria: April 5, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Hypertension; Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension
• Other Study ID Numbers: 7962-008; MK-7962-008 (Other Identifier: Merck); 2022-000478-25 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No