Clinical trial NCT05587712: Study to Evaluate Sotatercept (MK-7962) in Children With Pulmonary Arterial Hypertension (PAH) (MK-7962-008)
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Pulmonary Arterial Hypertension
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2022-10-20
Enrollment: 42
Sex: ALL
Minimum age (years): 1
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Serum Trough Concentration (Ctrough) of Sotatercept
timeFrame: 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
measure: Area Under the Curve at Steady State (AUCss) of Sotatercept
timeFrame: 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
measure: Area Under the Curve from 0 to 3 weeks (AUC0-3 weeks) of Sotatercept
timeFrame: Predose Day 1, Day 7, Day 14, and Predose Day 21
measure: Percentage of Participants Who Experience at Least 1 Adverse Event (AE)
timeFrame: Up to 24 weeks
measure: Percentage of Participants Who Discontinue Study Drug Due to an AE
timeFrame: Up to 24 weeks
measure: Laboratory Parameter (Hematology): Concentration of Hemoglobin
timeFrame: Up to 24 weeks
measure: Laboratory Parameter (Hematology): Hematocrit
timeFrame: Up to 24 weeks
measure: Laboratory Parameter (Hematology): Red Blood Cell (RBC) Count
timeFrame: Up to 24 weeks
measure: Laboratory Parameter (Hematology): Reticulocyte Count
timeFrame: Up to 24 weeks
measure: Laboratory Parameter (Hematology): Platelet Count
timeFrame: Up to 24 weeks
measure: Blood Pressure (BP)
timeFrame: Up to 24 weeks
measure: Titer of Anti-drug Antibody (ADA) to Sotatercept
timeFrame: Up to 24 weeks
Secondary outcomes:
measure: Mean Change from Baseline in 6-Minute Walk Distance (6MWD) (Cohorts 1 and 2)
timeFrame: Baseline and Week 24
measure: Mean Change from Baseline in Tricuspid Annular Plane Systolic Excursion (TAPSE)
timeFrame: Baseline and Week 24
measure: Mean Change from Baseline in Pulmonary Artery Systolic Pressure (PASP)
timeFrame: Baseline and Week 24
measure: Mean Change from Baseline in Right Ventricular Fractional Area Change (RVFAC)
timeFrame: Baseline and Week 24
measure: Mean Change from Baseline in Eccentricity Index
timeFrame: Baseline and Week 24
measure: Mean Change from Baseline in Right Ventricular (RV) Function (Cohorts 1 and 2)
timeFrame: Baseline and Week 24
measure: Mean Change from Baseline on Cardiac Output (Cohorts 1 and 2)
timeFrame: Baseline and Week 24
measure: Mean Change from Baseline in Pulmonary Arterial Pressure (PAP) (Cohorts 1 and 2)
timeFrame: Baseline and Week 24
measure: Mean Change from Baseline in Pediatric Quality of Life (PedsQL) Generic Score
timeFrame: Baseline and Week 24
measure: Mean Change from Baseline in N-terminal Prohormone B-type Natriuretic Peptide (NT-proBNP)
timeFrame: Baseline and Week 24
measure: Percentage of Participants Who Either Improved or Maintained Their World Health Organization Functional Class (WHO FC)
timeFrame: Baseline and Week 24
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: The Regents of the University of California - Los Angeles (UCLA Pediatrics) ( Site 1606)
state: California
city: Palo Alto
country: United States
facility: Stanford University School of Medicine ( Site 1603)
state: California
city: San Francisco
country: United States
facility: UCSF Benioff Children's Hospital San Francisco ( Site 1611)
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado ( Site 1609)
state: Colorado
city: Washington
country: United States
facility: Children's National Medical Center ( Site 1600)
state: District of Columbia
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center ( Site 1602)
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia (CHOP) ( Site 1608)
state: Pennsylvania
city: Nashville
country: United States
facility: Monroe Carell Jr. Children's Hospital ( Site 1601)
state: Tennessee
city: Seattle
country: United States
facility: Seattle Children's Hospital ( Site 1605)
state: Washington
city: Milwaukee
country: United States
facility: Children's Wisconsin ( Site 1610)
state: Wisconsin
city: Westmead
country: Australia
facility: The Children's Hospital at Westmead ( Site 0001)
state: New South Wales
city: Rionegro
country: Colombia
facility: Clinica Somer-Unidad de Investigacion y Docencia ( Site 0205)
state: Antioquia
city: Cali
country: Colombia
facility: Fundación Valle del Lili ( Site 0200)
state: Valle Del Cauca
city: Cali
country: Colombia
facility: Clínica Imbanaco S.A.S ( Site 0203)
state: Valle Del Cauca
city: Toulouse
country: France
facility: CHU de Toulouse - Hôpital des Enfants ( Site 0302)
state: Haute-Garonne
city: Marseille
country: France
facility: Assistance Publique Hôpitaux de Marseille - Hôpital de la Timone ( Site 0303)
state: Provence-Alpes-Cote-d Azur
city: Paris
country: France
facility: Hôpital Universitaire Necker Enfants Malades ( Site 0300)
city: Heidelberg
country: Germany
facility: Universitaetsklinikum Heidelberg ( Site 0401)
state: Baden-Wurttemberg
city: München
country: Germany
facility: Klinikum der Universität München Großhadern ( Site 0404)
state: Bayern
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover ( Site 0405)
state: Niedersachsen
city: Petah-Tikva
country: Israel
facility: Schneider Children's Medical Center ( Site 0603)
city: Ramat Gan
country: Israel
facility: Sheba Medical Center ( Site 0601)
city: Groningen
country: Netherlands
facility: University Medical Center Groningen ( Site 0900)
city: Warszawa
country: Poland
facility: Centrum Zdrowia Dziecka w Warszawie-Klinika Kardiologii ( Site 1103)
state: Mazowieckie
city: Gdańsk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne-Klinika Kardiologii Dziecięcej i Wad Wrodzonych Serca ( Site 1102)
state: Pomorskie
city: Johannesburg, Soweto
country: South Africa
facility: Wits Clinical Research-Wits Clinical Research Bara ( Site 1201)
state: Gauteng
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal ( Site 1300)
state: Madrid, Comunidad De
city: València
country: Spain
facility: Hospital Universitari i Politecnic La Fe ( Site 1303)
state: Valencia
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron ( Site 1302)
city: Madrid
country: Spain
facility: HOSPITAL GENERAL UNIVERSITARIO GREGORIO MARAÑON ( Site 1301)
city: Ankara
country: Turkey
facility: Hacettepe Universite Hastaneleri ( Site 1400)
city: Ankara
country: Turkey
facility: Gazi University Health Research and Application Center Gazi -Çocuk Sağlığı ve Hastalıkları Anabilim ( Site 1402)
city: Ankara
country: Turkey
facility: Ankara Bilkent Şehir Hastanesi. ( Site 1403)
city: Istanbul
country: Turkey
facility: Mehmet Akif Ersoy Research and Training Hospital ( Site 1404)
city: London
country: United Kingdom
facility: Great Ormond Street Hospital For Children NHS Foundation Trust ( Site 1500)
state: London, City Of
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: