129 Xenon Imaging in Patients Treated With Sotatercept (Sox-PH)

129Xenon MR Imaging and Spectroscopy Response to Sotatercept in Pulmonary Arterial Hypertension

Determine the ability of 129Xe MRI/MRS biomarker signatures to non-invasively monitor pulmonary vascular reverse remodeling induced by sotatercept in pulmonary arterial hypertension (PAH).

Study Overview

• Status: Recruiting
• Conditions: Pulmonary Arterial Hypertension; Pulmonary Hypertension
• Intervention / Treatment: Drug: 129Xe Hyperpolarized

Detailed Description

The researchers hypothesize that 129Xe MRI/MRS biomarker signatures of pulmonary vascular remodeling will predict short- and long-term response and efficacy to PAH patients who are receiving sotatercept as clinical standard-of-care. At baseline (prior to the treatment with sotatercept), 3, and 12 months of follow-up, the research team will perform 129Xe MRI/MRS scans. 129Xe MRI/MRS metrics, including: (1) 129Xe MRI ventilation defect (reflecting gas exchange abnormalities), (2)129Xe MRI RBC defect percentage (reflecting pulmonary capillary blood volume), (3) 129Xe MRI membrane uptake percentage (reflecting lung interstitial wall thick-ness and inflammation), and (4) 129Xe MRS oscillation amplitude (reflecting degree of pre/post-capillary PH) as well as standard-of-care assessments including labs, echocardiography, NTproBNP and 6MWD will be acquired at each visit. The investigators expect that 129Xe MRI/MRS biomarker signatures will improve prediction of treatment response and clinical outcomes (hospitalizations and death) compared to standard risk assessment with functional class, 6MWD, and NTproBNP.

This study would allow an assessment of sotatercept's role in promoting pulmonary vascular reverse remodeling. It could also improve outcome assessment in clinical trials to a biomarker that is more accurate and precise, thus allowing greater reliability in assessment of treatment effect and allowing smaller clinical trial size. Lastly, three-dimensional functional lung imaging could provide greater individualized assessment of lung function and tailoring of therapy, thus optimizing precision and personalized medicine.

PAH is characterized by obstructive vasculopathy of the pulmonary arterioles that results in right heart failure and death. The pulmonary vascular remodeling in PAH includes neointimal proliferation, medial hypertrophy, plexiform arteriopathy, and fibrosis; these changes can also differ between these subtypes. This results in specific changes in cardiac and pulmonary physiology, most notably: (1) an increase in the pulmonary vascular resistance (PVR) through the blood vessels due to their obstruction; and (2) a decrease in sur-face area and capillary blood volume for gas exchange through disruption of the normal capillary-alveolar interface with a decrease in the diffusion limit for carbon monoxide (DLCO). The increase in PVR results in increased afterload on the right heart, resulting in right ventricular (RV) dysfunction and failure. Similarly, gas exchange abnormalities contribute to decreased ventilatory efficiency and exercise limitation. Current treatments, which target the prostacyclin, endothelin-1, or nitric oxide pathways, slow disease progression. However, these drugs are thought to act largely through vasodilation, and not through remodeling. For that reason, the 5-year survival rate in PAH is still only approximately 60%, highlighting the need for therapies targeting pulmonary vascular remodeling pathways.

• Study Type: Interventional
• Enrollment (Estimated): 14
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Claudia Salazar; Phone Number: +1 919 660 2026; Email: claudia.salazar@duke.edu

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke University Medical Center
      • Principal Investigator: Sudarshan Rajagopal, MD, PhD
      • Contact: Claudia Salazar, BS; Phone Number: 919-660-2026; Email: claudia.salazar@duke.edu

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Outpatients of either gender, Age 18-75
2. Diagnosis of precapillary PH (right heart catheterization demonstrating hemodynamic criteria of a mean pulmonary artery pressure (mPAP) ≥ 20 mmHg, pulmonary vascular resistance ≥ 5 WU, pulmonary capillary wedge pressure ≤ 15 mmHg) in the setting of Group 1 (PAH)
3. Willing and giving informed consent and adhere to visit/protocol schedules (consent must be given before any study procedures are performed).
4. On a stable dose of background PAH therapy for > 90 days prior to study enrollment
5. Women of childbearing potential must have a negative urine pregnancy test before MRI

Exclusion Criteria:

1. Moderate to severe heart disease (LVEF < 45%, Severe LV hypertrophy, Moderate to severe valvular disease)
2. Chronic thromboembolic disease
3. PH due to schistosomiasis
4. Active cancer
5. Sickle cell anemia
6. Prisoners and pregnant women will not be approached for the study
7. Conditions that will prohibit MRI scanning (metal in eye, claustrophobia, inability to lie supine)
8. Medical or psychological conditions which, in the opinion of the investigator, might create undue risk to the participant or interfere with the participant's ability to comply with the protocol requirements

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Pulmonary Arterial Hypertension Patients Receving Sotatercept; PAH patients receiving sotatercept as treatment for their PAH	Drug: 129Xe Hyperpolarized; Each xenon dose will be limited to a volume less than 25% of participant lung capacity (TLC).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in Xenon MRI Red Blood Cell (RBC) percentage	baseline, 3,and 12 months
Change in cardiogenic oscillation amplitudes	baseline, 3, and 12 months

Collaborators and Investigators

• Sponsor: Bastiaan Driehuys
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: Sudarshan Rajagopal, MD, PhD, Duke University

Study record dates

Study Major Dates

• Study Start (Actual): October 27, 2025
• Primary Completion (Estimated): February 4, 2029
• Study Completion (Estimated): February 4, 2030

Study Registration Dates

• First Submitted: April 2, 2024
• First Submitted That Met QC Criteria: April 2, 2024
• First Posted (Actual): April 8, 2024

Study Record Updates

• Last Update Posted (Actual): February 24, 2026
• Last Update Submitted That Met QC Criteria: February 23, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: MRI; Xenon
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension; Pulmonary Arterial Hypertension; Hypertension, Pulmonary
• Other Study ID Numbers: Pro00115215

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
• product manufactured in and exported from the U.S.: No