129Xe Imaging for Pulmonary Arterial Hypertension

(Sox-PH Trial)

Overseen By Claudia Salazar

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Bastiaan Driehuys

Must be taking: PAH therapy

Disqualifiers: Heart disease, Cancer, Sickle cell, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method to evaluate how well the drug sotatercept works for people with pulmonary arterial hypertension (PAH), a condition characterized by high blood pressure in the lungs. Researchers use a special scan with 129Xe gas to observe lung changes without surgery. They seek participants diagnosed with PAH who have been on the same PAH treatment for at least 90 days. The study aims to determine if these new scans can help doctors understand the treatment's effects on the lungs. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you must be on a stable dose of your current PAH therapy for more than 90 days before joining the study.

What prior data suggests that 129Xe Hyperpolarized is safe for use in pulmonary arterial hypertension patients?

Research has shown that sotatercept is generally safe for people with pulmonary arterial hypertension (PAH). One study found that the drug remained safe over 2.5 years and even helped reduce death rates. Some side effects involve issues with blood and blood vessels, and new concerns have arisen about possible effects on the brain. However, the overall benefits seem to outweigh the risks for many patients. This suggests that sotatercept is relatively safe for people with PAH. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about 129Xe Hyperpolarized imaging because it offers a new way to understand and monitor Pulmonary Arterial Hypertension (PAH). Unlike current treatments that primarily focus on managing symptoms through medications like endothelin receptor antagonists and phosphodiesterase-5 inhibitors, this technique uses hyperpolarized xenon gas to provide detailed images of lung function. This innovative imaging method could help doctors see how well treatments are working and potentially catch changes in lung function earlier than traditional methods. By offering a clearer picture of the lungs, 129Xe imaging could lead to more personalized and effective treatment plans for PAH patients.

What evidence suggests that 129Xe Hyperpolarized is effective for monitoring pulmonary arterial hypertension?

Research has shown that sotatercept, which participants in this trial may receive, effectively treats pulmonary arterial hypertension (PAH). Studies have found that it improves heart function in PAH patients by affecting certain bodily processes. In one study, sotatercept lowered the risk of serious issues like death or hospitalization due to PAH. Patients experienced improvements within the first 24 weeks, and these benefits lasted for up to two years. Overall, sotatercept is considered safe, though some side effects, such as increased blood hemoglobin levels, have been noted. ^{1 6 7 8 9}

Who Is on the Research Team?

Sudarshan Rajagopal, MD, PhD

Principal Investigator

Duke University

Are You a Good Fit for This Trial?

This trial is for patients with Pulmonary Arterial Hypertension (PAH), a type of high blood pressure affecting the lungs. Specific eligibility criteria are not provided, but typically participants must meet certain health standards and may be required to have a confirmed diagnosis of PAH.

Inclusion Criteria

I have been on a consistent dose of PAH medication for over 90 days.

I have been diagnosed with a specific type of high blood pressure in the lungs.

Willing and giving informed consent and adhere to visit/protocol schedules (consent must be given before any study procedures are performed)

Exclusion Criteria

My cancer is currently active.

I have a long-term blood clotting condition.

My pulmonary hypertension is caused by schistosomiasis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Baseline 129Xe MRI/MRS scans and standard-of-care assessments are performed prior to treatment with sotatercept

1 visit

1 visit (in-person)

Treatment and Monitoring

Participants receive sotatercept and undergo 129Xe MRI/MRS scans and standard-of-care assessments at 3 months

3 months

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment with follow-up scans and assessments at 12 months

12 months

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• 129Xe Hyperpolarized

Trial Overview The study is testing how well a special type of lung imaging called '129 Xenon Imaging' can track changes in the lungs caused by Sotatercept treatment in PAH patients. This involves using MRI/MRS technology to create detailed images.

How Is the Trial Designed?

Group I: Pulmonary Arterial Hypertension Patients Receving Sotatercept Experimental Treatment 1 Intervention

PAH patients receiving sotatercept as treatment for their PAH

129Xe Hyperpolarized is already approved in United States for the following indications:

Approved in United States as Hyperpolarized 129Xe for:

• Pulmonary hypertension (investigational)

Who Is Running the Clinical Trial?

Bastiaan Driehuys

Lead Sponsor

Trials

15

Recruited

1,100+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Published Research Related to This Trial

Hyperpolarized (HP) (129)Xe MRI effectively identified significant pulmonary vascular disease (PVD) in two patients who had normal ventilation but decreased gas transfer, despite inconclusive results from other imaging methods.

The technique shows promise for diagnosing PVD and monitoring treatment responses, but further research is needed to establish its sensitivity and specificity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abnormalities in hyperpolarized (129)Xe magnetic resonance imaging and spectroscopy in two patients with pulmonary vascular disease. Dahhan, T., Kaushik, SS., He, M., et al.[2023]

This study is the first to use hyperpolarized 129Xe MRI to non-invasively assess pulmonary hypertension in a monocrotaline rat model, showing reduced gas exchange early in the disease and changes in tissue uptake later on.

The imaging results correlated well with histological findings, indicating that 129Xe MRI could be a valuable tool for monitoring disease progression and treatment response in pulmonary hypertension without the need for invasive procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantitative 129Xe MRI detects early impairment of gas-exchange in a rat model of pulmonary hypertension. Virgincar, RS., Nouls, JC., Wang, Z., et al.[2021]

Hyperpolarized 129Xe MRI (HypX-MRI) shows great promise as a new diagnostic tool, enhancing the detectability of lung structures and potentially allowing for better imaging of lipid-rich tissues, which has been challenging with traditional methods.

This technique could help identify issues like ventilation-perfusion mismatch in pulmonary diseases and may also be used for functional MRI studies of the brain, opening new avenues for understanding lung function and brain perfusion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of hyperpolarized noble gas MRI. Albert, MS., Balamore, D.[2019]

Hyperpolarized 129Xe gas is safe and well-tolerated as an inhaled contrast agent for MRI in children, with no serious adverse events reported during the study involving 28 participants aged 6 to 16 years.

While some children experienced mild and temporary changes in oxygen saturation and heart rate after inhalation, these effects were consistent with expected physiological responses and resolved quickly, indicating that 129Xe MRI is feasible for assessing lung function in pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility, tolerability and safety of pediatric hyperpolarized 129Xe magnetic resonance imaging in healthy volunteers and children with cystic fibrosis. Walkup, LL., Thomen, RP., Akinyi, TG., et al.[2022]

Hyperpolarized 129Xe MRI is a new imaging technique that allows for detailed lung imaging and can also detect 129Xe in the brain, providing insights into brain parenchyma and blood vessels.

The study outlines specific protocols for using 129Xe MRI in both rodents and humans, highlighting its potential for advanced medical imaging applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain Imaging Using Hyperpolarized 129Xe Magnetic Resonance Imaging. Chahal, S., Prete, BRJ., Wade, A., et al.[2019]

Inhalation of hyperpolarized xenon-129 (129Xe) was found to be safe and well tolerated among 44 subjects, including healthy individuals and patients with chronic obstructive pulmonary disease (COPD), with no serious adverse events reported.

While 91% of participants experienced mild and transient symptoms such as dizziness and euphoria, these symptoms resolved quickly without the need for clinical intervention, indicating that the procedure is generally safe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic obstructive pulmonary disease: safety and tolerability of hyperpolarized 129Xe MR imaging in healthy volunteers and patients. Driehuys, B., Martinez-Jimenez, S., Cleveland, ZI., et al.[2022]

The study introduces a new method for delivering hyperpolarized (129)Xe gas directly into the arterial blood of live rats using an extracorporeal circuit, allowing for continuous infusion and improved imaging capabilities.

This technique enables high-resolution, 3D MRI of lung ventilation and perfusion, facilitating detailed studies of the ventilation-perfusion ratio and potentially expanding the use of (129)Xe for functional imaging in other body areas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vivo MR imaging of pulmonary perfusion and gas exchange in rats via continuous extracorporeal infusion of hyperpolarized 129Xe. Cleveland, ZI., Möller, HE., Hedlund, LW., et al.[2021]

Hyperpolarized 129 Xenon-MRI (HP 129 Xe MRI) is a new imaging technique that can assess both how well air moves in and out of the lungs (ventilation) and how effectively gases are transferred in the lungs.

While most studies have focused on non-cancer lung diseases, HP 129 Xe MRI shows great potential for improving the management and understanding of lung cancer by evaluating these key lung functions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functional airway obstruction observed with hyperpolarized 129 Xenon-MRI. Song, EJ., Kelsey, CR., Driehuys, B., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40876858/

A New Frontier in Pulmonary Arterial Hypertension Treatment Data synthesis: The findings from this review indicate that sotatercept is an overall safe and effective option for improving PAH outcomes when ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2213558

Phase 3 Trial of Sotatercept for Treatment of Pulmonary ... Improvements were observed within the first 24 weeks of treatment and maintained over a period of 18 to 24 months with continued sotatercept therapy. In the ...

3. atsjournals.org atsjournals.org/doi/abs/10.1164/ajrccm.2025.211.Abstracts.A7602

Early Outcomes of Sotatercept in Pulmonary Arterial ... Mean RVFWS improved to -19% [-21% to -14.6%] (p = 0.032). Side effects were infrequent, except for an increment in Hb levels by a mean 1.92±1.4 g/dL (p<0.0001).

4. jwatch.org jwatch.org/na59304/2025/10/09/sotatercept-beneficial-recent-onset-pulmonary-arterial

Sotatercept Beneficial in Recent-Onset Pulmonary Arterial ... The activin-signaling inhibitor improved clinical outcomes in patients when given within 1 year of PAH diagnosis. ... PAH based on trials in those ...

5. acc.org acc.org/Latest-in-Cardiology/Clinical-Trials/2025/03/28/02/58/zenith

Sotatercept In High-Risk Patients With Pulmonary Arterial ... Treatment with sotatercept resulted in a lower risk of all-cause death, lung transplantation, and hospitalization (≥24 hours) for worsening PAH than placebo.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12496076/

Postmarketing analysis of sotatercept: identifying serious ... This study confirms sotatercept's labelled risks (haematological and vascular effects) and identifies novel safety concerns, including cerebral ...

7. publications.ersnet.org publications.ersnet.org/content/erj/66/4/2501633

Sotatercept in pulmonary arterial hypertension: revolution, risk ... Long-term safety data come from SOTERIA (Clinicaltrials.gov identifier NCT04796337), an ongoing open-label extension enrolling patients from PULSAR, STELLAR, ...

8. ajmc.com ajmc.com/view/sotatercept-for-pah-maintains-safety-reduced-mortality-in-long-term-follow-up

Sotatercept for PAH Maintains Safety, Reduced Mortality in ... The pulmonary arterial hypertension (PAH) drug preserved its safety profile at 2.5 years of treatment and continued to reduce mortality compared ...

9. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39978862/

A long-term follow-up study of sotatercept for treatment ... Interim results of SOTERIA support the favourable benefit-risk of add-on sotatercept treatment in adults with PAH. Follow-up reports from ...