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

Overview

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.

Interventions

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

Primary outcome measures

• Serum Trough Concentration (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 [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 [Time frame: Predose Day 1, Day 7, Day 14, and Predose Day 21]
• Percentage of Participants Who Experience at Least 1 Adverse Event (AE) [Time frame: Up to 24 weeks]
• Percentage of Participants Who Discontinue Study Drug Due to an AE [Time frame: Up to 24 weeks]
• Laboratory Parameter (Hematology): Concentration of Hemoglobin [Time frame: Up to 24 weeks]
• Laboratory Parameter (Hematology): Hematocrit [Time frame: Up to 24 weeks]
• Laboratory Parameter (Hematology): Red Blood Cell (RBC) Count [Time frame: Up to 24 weeks]
• Laboratory Parameter (Hematology): Reticulocyte Count [Time frame: Up to 24 weeks]
• Laboratory Parameter (Hematology): Platelet Count [Time frame: Up to 24 weeks]

Secondary outcome measures (11)

• Mean Change from Baseline in 6-Minute Walk Distance (6MWD) (Cohorts 1 and 2) [Time frame: Baseline and Week 24]
• Mean Change from Baseline in Tricuspid Annular Plane Systolic Excursion (TAPSE) [Time frame: Baseline and Week 24]
• Mean Change from Baseline in Pulmonary Artery Systolic Pressure (PASP) [Time frame: Baseline and Week 24]
• Mean Change from Baseline in Right Ventricular Fractional Area Change (RVFAC) [Time frame: Baseline and Week 24]
• Mean Change from Baseline in Eccentricity Index [Time frame: Baseline and Week 24]
• Mean Change from Baseline in Right Ventricular (RV) Function (Cohorts 1 and 2) [Time frame: Baseline and Week 24]
• Mean Change from Baseline on Cardiac Output (Cohorts 1 and 2) [Time frame: Baseline and Week 24]
• Mean Change from Baseline in Pulmonary Arterial Pressure (PAP) (Cohorts 1 and 2) [Time frame: Baseline and Week 24]
• Mean Change from Baseline in Pediatric Quality of Life (PedsQL) Generic Score [Time frame: Baseline and Week 24]
• Mean Change from Baseline in N-terminal Prohormone B-type Natriuretic Peptide (NT-proBNP) [Time frame: Baseline and Week 24]
• Percentage of Participants Who Either Improved or Maintained Their World Health Organization Functional Class (WHO FC) [Time frame: Baseline and Week 24]

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 10 centers

• The Regents of the University of California - Los Angeles (UCLA Pediatrics) ( Site 1606) — Los Angeles
• Stanford University School of Medicine ( Site 1603) — Palo Alto
• UCSF Benioff Children's Hospital San Francisco ( Site 1611) — San Francisco
• Children's Hospital Colorado ( Site 1609) — Aurora
• Children's National Medical Center ( Site 1600) — Washington D.C.
• Cincinnati Children's Hospital Medical Center ( Site 1602) — Cincinnati
• Children's Hospital of Philadelphia (CHOP) ( Site 1608) — Philadelphia
• Monroe Carell Jr. Children's Hospital ( Site 1601) — Nashville
• … and 2 more centers

Spain · 4 centers

• Hospital Universitario Ramón y Cajal ( Site 1300) — Madrid
• Hospital Universitari i Politecnic La Fe ( Site 1303) — Valencia
• Hospital Universitari Vall d'Hebron ( Site 1302) — Barcelona
• HOSPITAL GENERAL UNIVERSITARIO GREGORIO MARAÑON ( Site 1301) — Madrid

Turkey (Türkiye) · 4 centers

• Hacettepe Universite Hastaneleri ( Site 1400) — Ankara
• Gazi University Health Research and Application Center Gazi -Çocuk Sağlığı ve Hastalıkları — Ankara
• Ankara Bilkent Şehir Hastanesi. ( Site 1403) — Ankara
• Mehmet Akif Ersoy Research and Training Hospital ( Site 1404) — Istanbul

Colombia · 3 centers

• Clinica Somer-Unidad de Investigacion y Docencia ( Site 0205) — Rionegro
• Fundación Valle del Lili ( Site 0200) — Cali
• Clínica Imbanaco S.A.S ( Site 0203) — Cali

France · 3 centers

• CHU de Toulouse - Hôpital des Enfants ( Site 0302) — Toulouse
• Assistance Publique Hôpitaux de Marseille - Hôpital de la Timone ( Site 0303) — Marseille
• Hôpital Universitaire Necker Enfants Malades ( Site 0300) — Paris

Germany · 3 centers

• Universitaetsklinikum Heidelberg ( Site 0401) — Heidelberg
• Klinikum der Universität München Großhadern ( Site 0404) — München
• Medizinische Hochschule Hannover ( Site 0405) — Hanover

Israel · 2 centers

• Schneider Children's Medical Center ( Site 0603) — Petah Tikva
• Sheba Medical Center ( Site 0601) — Ramat Gan

Poland · 2 centers

• Centrum Zdrowia Dziecka w Warszawie-Klinika Kardiologii ( Site 1103) — Warsaw
• Uniwersyteckie Centrum Kliniczne-Klinika Kardiologii Dziecięcej i Wad Wrodzonych Serca ( S — Gdansk

Australia · 1 center

• The Children's Hospital at Westmead ( Site 0001) — Westmead

Netherlands · 1 center

• University Medical Center Groningen ( Site 0900) — Groningen

South Africa · 1 center

• Wits Clinical Research-Chris Hani Baragwanath Hospital ( Site 1201) — Johannesburg, Soweto

United Kingdom · 1 center

• Great Ormond Street Hospital For Children NHS Foundation Trust ( Site 1500) — London

Identifiers

NCT: NCT05587712 · 7962-008 · MK-7962-008 · 2023-504861-22-00 · U1111-1290-2858 · 2022-000478-25

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗