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

Pulmonary Arterial Hypertension Clinical Trial

— MOONBEAM  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05587712
• Other study ID #: 7962-008
• Secondary ID: MK-7962-0082022-
• Status: Recruiting
• Phase: Phase 2
• Start date: January 19, 2023
• Est. completion date: September 21, 2028

Study information

• Verified date: June 2024
• Source: Merck Sharp & Dohme LLC
• Contact: Toll Free Number
• Phone: 1-888-577-8839
• Email: Trialsites[@]merck.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 42
• Est. completion date: September 21, 2028
• Est. primary completion date: September 21, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 17 Years

Eligibility

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

Related Conditions & MeSH terms

• Familial Primary Pulmonary Hypertension
• Hypertension
• Pulmonary Arterial Hypertension

Intervention

Drug:
• Sotatercept
SC injection every 3 weeks (Q3W) of 0.3 mg/kg. Dosage may be adjusted based on protocol-specific guidelines.

Locations

Country	Name	City	State
Australia	The Children's Hospital at Westmead ( Site 0001)	Westmead	New South Wales
Colombia	Clínica Imbanaco S.A.S ( Site 0203)	Cali	Valle Del Cauca
Colombia	Fundación Valle del Lili ( Site 0200)	Cali	Valle Del Cauca
Colombia	Clinica Somer-Unidad de Investigacion y Docencia ( Site 0205)	Rionegro	Antioquia
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	CHU de Toulouse - Hôpital des Enfants ( Site 0302)	Toulouse	Haute-Garonne
Germany	Medizinische Hochschule Hannover ( Site 0405)	Hannover	Niedersachsen
Germany	Universitaetsklinikum Heidelberg ( Site 0401)	Heidelberg	Baden-Wurttemberg
Germany	Klinikum der Universität München Großhadern ( Site 0404)	München	Bayern
Israel	Schneider Children's Medical Center ( Site 0603)	Petah-Tikva
Israel	Sheba Medical Center ( Site 0601)	Ramat Gan
Netherlands	University Medical Center Groningen ( Site 0900)	Groningen
Poland	Uniwersyteckie Centrum Kliniczne-Klinika Kardiologii Dzieciecej i Wad Wrodzonych Serca ( Site 1102)	Gdansk	Pomorskie
Poland	Centrum Zdrowia Dziecka w Warszawie-Klinika Kardiologii ( Site 1103)	Warszawa	Mazowieckie
South Africa	Wits Clinical Research-Wits Clinical Research Bara ( Site 1201)	Johannesburg, Soweto	Gauteng
Spain	Hospital Universitari Vall d'Hebron ( Site 1302)	Barcelona
Spain	HOSPITAL GENERAL UNIVERSITARIO GREGORIO MARAÑON ( Site 1301)	Madrid
Spain	Hospital Universitario Ramón y Cajal ( Site 1300)	Madrid	Madrid, Comunidad De
Spain	Hospital Universitari i Politecnic La Fe ( Site 1303)	València	Valencia
Turkey	Ankara Bilkent Sehir Hastanesi. ( Site 1403)	Ankara
Turkey	Gazi University Health Research and Application Center Gazi -Çocuk Sagligi ve Hastaliklari Anabilim	Ankara
Turkey	Hacettepe Universite Hastaneleri ( Site 1400)	Ankara
Turkey	Mehmet Akif Ersoy Research and Training Hospital ( Site 1404)	Istanbul
United Kingdom	Great Ormond Street Hospital For Children NHS Foundation Trust ( Site 1500)	London	London, City Of
United States	Children's Hospital Colorado ( Site 1609)	Aurora	Colorado
United States	Cincinnati Children's Hospital Medical Center ( Site 1602)	Cincinnati	Ohio
United States	The Regents of the University of California - Los Angeles (UCLA Pediatrics) ( Site 1606)	Los Angeles	California
United States	Children's Wisconsin ( Site 1610)	Milwaukee	Wisconsin
United States	Monroe Carell Jr. Children's Hospital ( Site 1601)	Nashville	Tennessee
United States	Stanford University School of Medicine ( Site 1603)	Palo Alto	California
United States	Children's Hospital of Philadelphia (CHOP) ( Site 1608)	Philadelphia	Pennsylvania
United States	UCSF Benioff Children's Hospital San Francisco ( Site 1611)	San Francisco	California
United States	Seattle Children's Hospital ( Site 1605)	Seattle	Washington
United States	Children's National Medical Center ( Site 1600)	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Australia,  Colombia,  France,  Germany,  Israel,  Netherlands,  Poland,  South Africa,  Spain,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	Titer of Anti-drug Antibody (ADA) to Sotatercept	ADA to Sotatercept will be assessed.	Up to 24 weeks
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

•   Merck Clinical Trials Information
•   Plain Language Summary