A Study of Sotatercept in Japanese Pulmonary Arterial Hypertension (PAH) Participants (MK-7962-020)

Pulmonary Arterial Hypertension Clinical Trial

Official title:

A Phase 3 Non-randomized, Non-controlled, Open Label Clinical Study to Evaluate the Efficacy and Safety of MK-7962 (Sotatercept) add-on to Background Therapy in Japanese Participants With Pulmonary Arterial Hypertension (PAH)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05818137
• Other study ID #: 7962-020
• Secondary ID: jRCT2031230046MK
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: May 10, 2023
• Est. completion date: August 13, 2025

Study information

• Verified date: May 2024
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This local Phase 3 study is planned to confirm the efficacy and safety in Japanese PAH participants. The primary population of this study is Japanese PAH participants with World Health Organization Functional Class (WHO FC) II or III while the study includes PAH participants with WHO FC I or IV as other populations. There are no hypotheses for this study.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 46
• Est. completion date: August 13, 2025
• Est. primary completion date: March 12, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Documented diagnostic RHC at any time prior to screening confirming the diagnosis of

WHO PAH Group 1 in any of the following subtypes:

• Idiopathic PAH
• Heritable PAH
• Drug/toxin-induced PAH
• PAH associated with connective tissue disease
• PAH associated with simple, congenital systemic-to-pulmonary shunts at least 1 year following repair
• PAH classified as WHO FC I or symptomatic PAH classified as WHO FC II to IV
• On stable doses of background PAH therapy and diuretics (if applicable) for at least 90 days prior to screening. Exclusion Criteria
• Diagnosis of PH WHO Groups 2, 3, 4, or 5.
• Diagnosis of the following PAH Group 1 subtypes:
• human immunodeficiency virus (HIV)-associated PAH
• PAH associated with portal hypertension
• schistosomiasis-associated PAH
• PAH with features of significant venous/capillary pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis (PVOD/PCH) involvement
• Is on the waiting list for lung transplant
• Pregnant or breastfeeding women.
• History of full or partial pneumonectomy.
• Pulmonary function test (PFT) values of forced vital capacity (FVC) < 60% predicted at the screening visit or within 6 months prior to the screening visit.
• Initiation of an exercise program for cardiopulmonary rehabilitation within 90 days prior to the screening visit or planned initiation during the study.
• History of more than mild obstructive sleep apnea that is untreated.
• Known history of portal hypertension or chronic liver disease, including hepatitis B and/or hepatitis C (with evidence of recent infection and/or active virus replication), defined as mild to severe hepatic impairment.
• History of restrictive, constrictive, or congestive cardiomyopathy.
• History of atrial septostomy within 180 days prior to the screening visit.
• Personal or family history of long QT syndrome (LQTS) or sudden cardiac death.
• Left ventricular ejection fraction (LVEF) < 45% on historical ECHO within 6 months prior to the screening visit.
• Any symptomatic coronary disease events within 6 months prior to the screening visit.
• Cerebrovascular accident within 3 months prior to the screening visit.
• Significant (= 2+ regurgitation) mitral regurgitation or aortic regurgitation valvular disease, mitral stenosis and more than mild aortic valve stenosis.
• Prior exposure to sotatercept or luspatercept or history of allergic or anaphylactic reaction or hypersensitivity to recombinant proteins or excipients in investigational product.
• Received intravenous inotropes (e.g., dobutamine, dopamine, norepinephrine, vasopressin) within 30 days prior to the screening visit.
• Currently enrolled in or have completed any other investigational product study within 30 days.
• Weight at the screening is over 85 kg.

Related Conditions & MeSH terms

• Familial Primary Pulmonary Hypertension
• Hypertension
• Pulmonary Arterial Hypertension

Intervention

Biological:
• Sotatercept
SC injection at a starting dose of 0.3 mg/kg with a target dose of 0.7 mg/kg every 21 days plus background PAH therapy.

Locations

Country	Name	City	State
Japan	The University of Tokyo Hospital ( Site 2006)	Bunkyo-ku	Tokyo
Japan	Chiba University Hospital ( Site 2003)	Chiba
Japan	Kyushu University Hospital ( Site 2015)	Fukuoka
Japan	Hamamatsu University Hospital ( Site 2016)	Hamamatsu	Shizuoka
Japan	Kobe University Hospital ( Site 2012)	Kobe	Hyogo
Japan	Kure Kyosai Hospital ( Site 2017)	Kure	Hiroshima
Japan	Kurume University Hospital ( Site 2014)	Kurume	Fukuoka
Japan	Kyorin University Hospital ( Site 2005)	Mitaka	Tokyo
Japan	Nagoya University Hospital ( Site 2010)	Nagoya-Shi	Aichi
Japan	Chiba Saiseikai Narashino hospital ( Site 2004)	Narashino	Chiba
Japan	National Hospital Organization Okayama Medical Center ( Site 2013)	Okayama
Japan	Hokkaido University Hospital ( Site 2001)	Sapporo	Hokkaido
Japan	Sapporo Medical University Hospital ( Site 2018)	Sapporo	Hokkaido
Japan	Tohoku University Hospital ( Site 2002)	Sendai-shi	Miyagi
Japan	National Cerebral and Cardiovascular Center ( Site 2011)	Suita	Osaka
Japan	International University of Health and Welfare Mita Hospital ( Site 2008)	Tokyo
Japan	Keio university hospital ( Site 2007)	Tokyo

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from Pulmonary Vascular Resistance (PVR) from Baseline at Week 24	PVR is the resistance against blood flow from the pulmonary artery to the left atrium. PVR is measured in dyn·sec/cm^5 by right heart catheterization (RHC). RHC will be performed during the screening period (baseline) and Week 24. The change in PVR from baseline at Week 24 will be presented.	Baseline and Week 24
Primary	Number of Participants experiencing Adverse Events (AEs)	An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants experiencing AEs will be reported.	Up to ~24 weeks
Primary	Number of Participants who Discontinue Study Intervention due to AEs	An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants discontinuing study treatment due to AEs will be reported.	Up to ~24 weeks
Secondary	Change from baseline in Six-minute walk distance (6MWD) at Week 24	The distance walked in meters in 6 minutes will be measured during the screening period (baseline) and at Week 24. The change from baseline in 6MWD at Week 24 will be presented.	Baseline and Week 24
Secondary	Percentage of participants with improvement in World Health Organization Functional Class (WHO FC) at Week 24	Participants will have their pulmonary hypertension measured and classified during the screening period (baseline) and Week 24 as one of four categories of the WHO FC assessment ranging from I = no symptoms of pulmonary arterial hypertension with exercise or at rest to IV = symptoms at rest and severe symptoms with any activity. The percentage of participants with improvement in WHO FC at Week 24 will be presented.	Baseline and Week 24
Secondary	Change from baseline in N-terminal proB-type natriuretic peptide (NT-proBNP) at Week 24	NT-proBNP is an established marker of ventricular dysfunction in participants with PAH. NT-proBNP will be measured at Day 1 (baseline) and at Week 24. The change from baseline in NT-proBNP at Week 24 will be presented.	Baseline and Week 24

External Links

•   Merck Clinical Trials Information