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

Primary Purpose

Pulmonary Arterial Hypertension

Status
Active
Phase
Phase 3
Locations
Japan
Study Type
Interventional
Intervention
Sotatercept
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pulmonary Arterial Hypertension

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Nagoya University Hospital ( Site 2010)
  • Chiba Saiseikai Narashino hospital ( Site 2004)
  • Kurume University Hospital ( Site 2014)
  • Kure Kyosai Hospital ( Site 2017)
  • Sapporo Medical University Hospital ( Site 2018)
  • Hokkaido University Hospital ( Site 2001)
  • Kobe University Hospital ( Site 2012)
  • Tohoku University Hospital ( Site 2002)
  • National Cerebral and Cardiovascular Center ( Site 2011)
  • Hamamatsu University Hospital ( Site 2016)
  • The University of Tokyo Hospital ( Site 2006)
  • Kyorin University Hospital ( Site 2005)
  • Chiba University Hospital ( Site 2003)
  • Kyushu University Hospital ( Site 2015)
  • National Hospital Organization Okayama Medical Center ( Site 2013)
  • International University of Health and Welfare Mita Hospital ( Site 2008)
  • Keio university hospital ( Site 2007)

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Sotatercept

Arm Description

Participants on background PAH therapy will receive sotatercept subcutaneous (SC) injections at a starting dose of 0.3 mg/kg with a target dose of 0.7 mg/kg every 3 weeks up to 24 weeks. Thereafter, participants may choose to continue receiving the treatment until approval of sotatercept in Japan.

Outcomes

Primary Outcome Measures

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.
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.
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.

Secondary Outcome Measures

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.
Proportion of participants with improvement in WHO FC or maintenance of WHO FC II (in participants with WHO FC II at baseline)/WHO FC I (in participants with WHO FC I at baseline) 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 proportion of participants with improvement or maintenance in WHO FC at Week 24 will be presented.
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.

Full Information

First Posted
April 5, 2023
Last Updated
October 11, 2023
Sponsor
Merck Sharp & Dohme LLC
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1. Study Identification

Unique Protocol Identification Number
NCT05818137
Brief Title
A Study of Sotatercept in Japanese Pulmonary Arterial Hypertension (PAH) Participants (MK-7962-020)
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)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
May 10, 2023 (Actual)
Primary Completion Date
March 11, 2024 (Anticipated)
Study Completion Date
August 13, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Arterial Hypertension

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
35 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Sotatercept
Arm Type
Experimental
Arm Description
Participants on background PAH therapy will receive sotatercept subcutaneous (SC) injections at a starting dose of 0.3 mg/kg with a target dose of 0.7 mg/kg every 3 weeks up to 24 weeks. Thereafter, participants may choose to continue receiving the treatment until approval of sotatercept in Japan.
Intervention Type
Biological
Intervention Name(s)
Sotatercept
Other Intervention Name(s)
MK-7962, ActRIIA-IgG1Fc, ACE-011
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change from Pulmonary Vascular Resistance (PVR) from Baseline at Week 24
Description
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.
Time Frame
Baseline and Week 24
Title
Number of Participants experiencing Adverse Events (AEs)
Description
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.
Time Frame
Up to ~24 weeks
Title
Number of Participants who Discontinue Study Intervention due to AEs
Description
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.
Time Frame
Up to ~24 weeks
Secondary Outcome Measure Information:
Title
Change from baseline in Six-minute walk distance (6MWD) at Week 24
Description
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.
Time Frame
Baseline and Week 24
Title
Proportion of participants with improvement in WHO FC or maintenance of WHO FC II (in participants with WHO FC II at baseline)/WHO FC I (in participants with WHO FC I at baseline) at Week 24
Description
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 proportion of participants with improvement or maintenance in WHO FC at Week 24 will be presented.
Time Frame
Baseline and Week 24
Title
Change from baseline in N-terminal proB-type natriuretic peptide (NT-proBNP) at Week 24
Description
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.
Time Frame
Baseline and Week 24

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
Facility Information:
Facility Name
Nagoya University Hospital ( Site 2010)
City
Nagoya-Shi
State/Province
Aichi
ZIP/Postal Code
466-8560
Country
Japan
Facility Name
Chiba Saiseikai Narashino hospital ( Site 2004)
City
Narashino
State/Province
Chiba
ZIP/Postal Code
275-8580
Country
Japan
Facility Name
Kurume University Hospital ( Site 2014)
City
Kurume
State/Province
Fukuoka
ZIP/Postal Code
830-0011
Country
Japan
Facility Name
Kure Kyosai Hospital ( Site 2017)
City
Kure
State/Province
Hiroshima
ZIP/Postal Code
7378505
Country
Japan
Facility Name
Sapporo Medical University Hospital ( Site 2018)
City
Sapporo
State/Province
Hokkaido
ZIP/Postal Code
060-8543
Country
Japan
Facility Name
Hokkaido University Hospital ( Site 2001)
City
Sapporo
State/Province
Hokkaido
ZIP/Postal Code
060-8648
Country
Japan
Facility Name
Kobe University Hospital ( Site 2012)
City
Kobe
State/Province
Hyogo
ZIP/Postal Code
650-0017
Country
Japan
Facility Name
Tohoku University Hospital ( Site 2002)
City
Sendai-shi
State/Province
Miyagi
ZIP/Postal Code
980-8574
Country
Japan
Facility Name
National Cerebral and Cardiovascular Center ( Site 2011)
City
Suita
State/Province
Osaka
ZIP/Postal Code
564-8565
Country
Japan
Facility Name
Hamamatsu University Hospital ( Site 2016)
City
Hamamatsu
State/Province
Shizuoka
ZIP/Postal Code
431-3192
Country
Japan
Facility Name
The University of Tokyo Hospital ( Site 2006)
City
Bunkyo-ku
State/Province
Tokyo
ZIP/Postal Code
113-8654
Country
Japan
Facility Name
Kyorin University Hospital ( Site 2005)
City
Mitaka
State/Province
Tokyo
ZIP/Postal Code
181-8611
Country
Japan
Facility Name
Chiba University Hospital ( Site 2003)
City
Chiba
ZIP/Postal Code
260-8677
Country
Japan
Facility Name
Kyushu University Hospital ( Site 2015)
City
Fukuoka
ZIP/Postal Code
812-8582
Country
Japan
Facility Name
National Hospital Organization Okayama Medical Center ( Site 2013)
City
Okayama
ZIP/Postal Code
701-1192
Country
Japan
Facility Name
International University of Health and Welfare Mita Hospital ( Site 2008)
City
Tokyo
ZIP/Postal Code
108-8329
Country
Japan
Facility Name
Keio university hospital ( Site 2007)
City
Tokyo
ZIP/Postal Code
1608582
Country
Japan

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Links:
URL
https://www.merckclinicaltrials.com/
Description
Merck Clinical Trials Information

Learn more about this trial

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

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