Sotatercept on Central Cardiopulmonary Performance and Peripheral Oxygen Transport During Exercise in Pulmonary Arterial Hypertension

Effect of Sotatercept on Central Cardiopulmonary Performance and Peripheral Oxygen Transport During Exercise in Pulmonary Arterial Hypertension

The purpose of this study is to see if the drug sotatercept given for 36 weeks improves the functioning of the heart and improves quality of life.

Study Overview

• Status: Not yet recruiting
• Conditions: Pulmonary Arterial Hypertension
• Intervention / Treatment: Drug: Sotatercept

• Study Type: Interventional
• Enrollment (Estimated): 21
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Yogesh Reddy, MBBS; Phone Number: 507-284-3687; Email: Reddy.Yogesh@mayo.edu

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

• Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial.
• NYHA Class II-IV.
• LVEF ≥ 40 % within the preceding year.
• No recent initiation of pulmonary vasodilator in the last 60 days.
• Pulmonary arterial hypertension by right heart catheterization (Mean PA pressure ≥ 20 mmHg with PVR>2 Wood units) with no evidence of heart failure with preserved ejection fraction (exercise PCWP <25 mm Hg).
• Symptomatic PAH patients with plan to undergo exercise RHC for reassessment of exertional symptoms.

Exclusion Criteria

• Myocardial infarction, stroke, hospitalization for heart failure, unstable angina pectoris or transient ischemic attack within 30 days prior to the day of screening.
• Planned coronary, carotid, or peripheral artery revascularization.
• Any other condition judged by the investigator to be the primary cause of dyspnea (such as heart failure due to restrictive cardiomyopathy or infiltrative conditions (e.g., amyloidosis), hypertrophic obstructive cardiomyopathy, anemia, or more than moderate mitral or aortic heart valve disease).
• Wheelchair bound or orthopedic inability to exercise.
• Chronic hypoxemia with inability to exercise without oxygen supplementation.
• Skeletal muscle myopathy.
• History of rhabdomyolysis.
• Participation in any clinical trial of an approved or non-approved device for the treatment of pulmonary hypertension within 30 days before screening.
• Receipt of any investigational medicinal product within 30 days before screening.
• Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using a highly effective contraceptive method.
• Major surgery scheduled for the duration of the trial, affecting walking ability in the opinion of the investigator.
• Any disorder, including severe psychiatric disorder, suicidal behavior within 90 days before screening, and suspected drug abuse, which in the investigator´s opinion might jeopardize subject´s safety or compliance with the protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sotatercept Therapy; All participants will receive 36 weeks of sotatercept therapy. Sotatercept is administered as a subcutaneous injection once every 3 weeks.	Drug: Sotatercept; As per FDA indications, sotatercept will be administered as 0.3 mg/kg injection for the first dose followed by 0.7 mg/kg injections for subsequent doses.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pulmonary arterial mean pressure/Cardiac Output (PA/CO) at peak exercise	Peak exercise pulmonary arterial mean pressure/ Cardiac output (mm Hg/L/min)	Baseline, Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Oxygen Consumption (VO2)	VO2 will be measured in mL/kg/min. It will be directly measured using expired gas analysis.	Baseline, 24 weeks
Single leg blood flow at peak exercise	Single leg blood flow will be obtained from venous access. Single leg blood flow will be measured in ml/min	Baseline, 24 weeks
Pulmonary vascular resistance at rest	Pulmonary vascular resistance will be measured in Wood units (mmHg/L/min)	Baseline, 24 weeks
Pulmonary vascular resistance at peak exercise	Pulmonary vascular resistance will be measured in Wood units (mmHg/L/min)	Baseline, 24 weeks
Pulmonary arterial (PA) compliance at rest	PA compliance measures pulmonary arterial distensibility and will be recorded at Baseline and 24 Weeks. PA compliance will be measured in ml/mm Hg.	Baseline, 24 weeks
Pulmonary arterial (PA) compliance at peak exercise	PA compliance measures pulmonary arterial distensibility and will be recorded at Baseline and 24 Weeks. PA compliance will be measured in ml/mm Hg.	Baseline, 24 weeks
Pulmonary arterial elastance at rest	PA elastance measures pulmonary artery stiffness and will be recorded at baseline and 24 weeks as PA systolic pressure/stroke volume (units mm Hg/ml)	Baseline, 24 weeks
Pulmonary arterial elastance at peak exercise	PA elastance measures pulmonary artery stiffness and will be recorded at baseline and 24 weeks as PA systolic pressure/stroke volume (units mm Hg/ml)	Baseline, 24 weeks
Left ventricular (LV) transmural pressure at rest	LV transmural pressure will measured by catheterization at Baseline and 24 Weeks as the difference between pulmonary capillary wedge pressure and right atrial pressure	Baseline, 24 weeks
Left ventricular (LV) transmural pressure at peak exercise	LV transmural pressure will measured by catheterization at Baseline and 24 Weeks as the difference between pulmonary capillary wedge pressure and right atrial pressure	Baseline, 24 weeks
Right Ventricular Pulmonary Artery Coupling at rest	Calculated as the ratio of RV function by echocardiography indexed to PA systolic pressure (unit mmHg-1)	Baseline, 24 weeks
Right Ventricular Pulmonary Artery Coupling at peak exercise	Calculated as the ratio of RV function by echocardiography indexed to PA systolic pressure (unit mmHg-1)	Baseline, 24 weeks
Eccentricity index at rest	Eccentricity index will be calculated as the ratio of antero posterior and septolateral dimension of the left ventricle by echocardiogram	Baseline, 24 weeks
Eccentricity index at peak exercise	Eccentricity index will be calculated as the ratio of antero posterior and septolateral dimension of the left ventricle by echocardiogram	Baseline, 24 weeks
Right atrial pressure (RA) at rest	RA pressure (mm Hg) will be measured by catheterization conducted at Baseline and 24 weeks	Baseline, 24 weeks
Right atrial pressure (RA) at peak exercise	RA pressure (mm Hg) will be measured by catheterization conducted at Baseline and 24 weeks	Baseline, 24 weeks
Change in skeletal muscle O2 diffusive conductance (Dm) during peak exercise	Dm is measured in ml/mm Hg/min during peak exercise	Baseline, 24 weeks
Change in skeletal muscle O2 diffusive conductance (Dm) during single leg exercise	Dm is measured in ml/mm Hg/min during single leg exercise	Baseline, 24 weeks

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Yogesh Reddy, MBBS, Mayo Clinic

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): February 1, 2025
• Study Completion (Estimated): February 1, 2025

Study Registration Dates

• First Submitted: May 7, 2024
• First Submitted That Met QC Criteria: May 7, 2024
• First Posted (Actual): May 10, 2024

Study Record Updates

• Last Update Posted (Actual): May 10, 2024
• Last Update Submitted That Met QC Criteria: May 7, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Hypertension; Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension
• Other Study ID Numbers: 24-002570

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No