129Xe Imaging for Pulmonary Arterial Hypertension

(Sox-PH Trial)

Overseen By David Ptashnik, MS

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

14 Participants Needed

Trial Summary

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 data supports the effectiveness of the treatment 129Xe Hyperpolarized for Pulmonary Arterial Hypertension?

Research shows that hyperpolarized 129Xe MRI can detect early changes in lung function related to pulmonary hypertension in animal models, suggesting it might help monitor the disease and assess treatment response in humans. ^{1 2 3 4 5}

Is hyperpolarized 129Xe MRI safe for humans?

Research shows that hyperpolarized 129Xe MRI has been safely used in both healthy volunteers and patients with conditions like cystic fibrosis and chronic obstructive pulmonary disease. It involves inhaling a gas and holding your breath for a short time, which has been well-tolerated in studies. ^{2 3 4 6 7}

How does the treatment 129Xe Hyperpolarized differ from other treatments for pulmonary arterial hypertension?

The treatment 129Xe Hyperpolarized is unique because it uses a special type of MRI that involves hyperpolarized xenon gas to non-invasively image and assess lung function and gas exchange, which can help monitor the progression of pulmonary arterial hypertension and potentially assess response to therapy. Unlike traditional treatments, it provides detailed imaging of lung ventilation and gas transfer without invasive procedures. ^{2 3 4 8 9}

What is the purpose of this trial?

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).

Research Team

Sudarshan Rajagopal, MD, PhD

Principal Investigator

Duke University

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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

Findings from Research

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 (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]

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]

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 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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Noninvasive diagnosis of pulmonary hypertension with hyperpolarised 129Xe magnetic resonance imaging and spectroscopy. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Quantitative 129Xe MRI detects early impairment of gas-exchange in a rat model of pulmonary hypertension. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Abnormalities in hyperpolarized (129)Xe magnetic resonance imaging and spectroscopy in two patients with pulmonary vascular disease. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Brain Imaging Using Hyperpolarized 129Xe Magnetic Resonance Imaging. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

In vivo MR imaging of pulmonary perfusion and gas exchange in rats via continuous extracorporeal infusion of hyperpolarized 129Xe. [2021]

6. Germany pubmed.ncbi.nlm.nih.gov

Feasibility, tolerability and safety of pediatric hyperpolarized 129Xe magnetic resonance imaging in healthy volunteers and children with cystic fibrosis. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Chronic obstructive pulmonary disease: safety and tolerability of hyperpolarized 129Xe MR imaging in healthy volunteers and patients. [2022]

8. Australia pubmed.ncbi.nlm.nih.gov

Functional airway obstruction observed with hyperpolarized 129 Xenon-MRI. [2022]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Development of hyperpolarized noble gas MRI. [2019]