Sotatercept for Pulmonary Arterial Hypertension

Overseen By Yogesh Reddy, MBBS

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Mayo Clinic

Disqualifiers: Recent heart attack, Stroke, Anemia, 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 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 36 weeks

21 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if the drug sotatercept can improve heart function and overall quality of life for people with pulmonary arterial hypertension (high blood pressure in the lungs). Participants will receive sotatercept injections every three weeks for a total of 36 weeks. The trial seeks participants diagnosed with pulmonary arterial hypertension who experience symptoms such as difficulty breathing during exercise. As a Phase 4 trial, sotatercept has already received FDA approval and proven effective; this research seeks to understand its benefits for more patients.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that you should not have started a new pulmonary vasodilator in the last 60 days.

What is the safety track record for sotatercept?

Research has shown that sotatercept is generally safe for people with pulmonary arterial hypertension (PAH). Studies have found that it improves health outcomes without causing serious side effects. For example, one study found that patients taking sotatercept had a lower risk of death, needing a lung transplant, and being hospitalized compared to those who did not take it.

Another study reported that an independent safety committee reviewed sotatercept and found no major safety concerns after patients received their first dose. This indicates that sotatercept is well-tolerated by patients with PAH.

Additionally, the FDA has approved sotatercept for treating PAH, which supports its safety. Overall, the evidence shows that sotatercept is a promising and safe option for managing PAH. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Sotatercept is unique because it targets the underlying disease process of pulmonary arterial hypertension (PAH) in a novel way. Unlike standard treatments that mainly dilate blood vessels, sotatercept acts on the transforming growth factor-beta (TGF-β) superfamily pathways, which are involved in cell growth and repair. This mechanism offers the potential to not only manage symptoms but also modify the disease itself, which has researchers excited about its potential long-term benefits for patients with PAH. Additionally, sotatercept is administered as a convenient subcutaneous injection every three weeks, potentially improving adherence and quality of life compared to daily oral medications.

What evidence suggests that sotatercept might be an effective treatment for pulmonary arterial hypertension?

Research shows that sotatercept may help treat pulmonary arterial hypertension (PAH). Studies have found that it can enhance exercise capacity and heart function. It also improves the WHO functional class, a measure of symptom severity. Additionally, sotatercept lowers the risk of the condition worsening, helping to slow PAH progression. These findings suggest that sotatercept is an effective option for improving outcomes in people with PAH. Participants in this trial will receive 36 weeks of sotatercept therapy to further evaluate its effectiveness. ^{1 2 4 6 7}

Who Is on the Research Team?

Yogesh Reddy, MBBS

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for individuals with Pulmonary Arterial Hypertension (PAH), a type of high blood pressure affecting the arteries in the lungs and heart. Participants should have PAH diagnosis and meet specific health criteria not detailed here.

Inclusion Criteria

I haven't started any new lung blood pressure medication in the last 60 days.

Informed consent obtained before any trial-related activities

LVEF ≥ 40 % within the preceding year

Exclusion Criteria

I haven't had a heart attack, stroke, or severe heart issues in the last 30 days.

I am scheduled for a procedure to improve blood flow to my heart, neck, or limbs.

I am not pregnant, breastfeeding, planning to become pregnant, or if I can have children, I am using effective birth control.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive sotatercept therapy administered as a subcutaneous injection once every 3 weeks for 36 weeks

36 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Sotatercept

Trial Overview The study tests if sotatercept, administered over 36 weeks, can enhance heart function and quality of life in PAH patients. It's an investigation into the drug's long-term effects on cardiopulmonary performance during exercise.

How Is the Trial Designed?

Group I: Sotatercept Therapy Experimental Treatment 1 Intervention

All participants will receive 36 weeks of sotatercept therapy. Sotatercept is administered as a subcutaneous injection once every 3 weeks.

Sotatercept is already approved in European Union, United States for the following indications:

Approved in European Union as Winrevair for:

• Pulmonary arterial hypertension (PAH, WHO Group 1)

Approved in United States as Winrevair for:

• Pulmonary arterial hypertension (PAH, WHO Group 1)

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Published Research Related to This Trial

SOM230, a somatostatin analogue, significantly improved survival rates in mice with bleomycin-induced lung fibrosis (69% vs 44%) and reduced lung collagen content, indicating its potential efficacy in treating pulmonary fibrosis.

The study demonstrated that SOM230 not only decreased inflammation and collagen production in mouse lungs but also inhibited the activation of human lung fibroblasts in vitro, suggesting a promising mechanism for its antifibrotic properties.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activation of somatostatin receptors attenuates pulmonary fibrosis. Borie, R., Fabre, A., Prost, F., et al.[2014]

In a study involving 106 participants with pulmonary arterial hypertension, sotatercept demonstrated significant long-term efficacy in reducing pulmonary vascular resistance and improving functional outcomes over 24 months, with sustained benefits observed in both groups receiving sotatercept.

The treatment was generally safe, with serious adverse events occurring in 30.8% of participants, but only a small number (2.9%) of deaths were reported, none linked to the drug, indicating a favorable safety profile for long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sotatercept for the treatment of pulmonary arterial hypertension: PULSAR open-label extension. Humbert, M., McLaughlin, V., Gibbs, JSR., et al.[2023]

Pasireotide long-acting release (LAR) formulation was well tolerated in patients with advanced gastroenteropancreatic neuroendocrine tumors (GEP NET), with 81% of participants reporting adverse events, primarily mild symptoms like diarrhea and fatigue.

The study achieved steady-state plasma levels of pasireotide after three monthly injections, indicating effective drug delivery and potential for sustained therapeutic effects in patients refractory to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, tolerability, pharmacokinetics, and pharmacodynamics of a long-acting release (LAR) formulation of pasireotide (SOM230) in patients with gastroenteropancreatic neuroendocrine tumors: results from a randomized, multicenter, open-label, phase I study. Wolin, EM., Hu, K., Hughes, G., et al.[2022]

The phase 3 STELLAR trial indicated that adding sotatercept to background therapy for pulmonary arterial hypertension (PAH) significantly increases life expectancy, with an estimated gain of 11.5 years per patient compared to background therapy alone.

Sotatercept also reduces the need for infused prostacyclin treatments, hospitalizations due to PAH, and the number of lung/heart-lung transplants required, suggesting it may improve overall patient management in PAH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population Health Model Predicting the Long-Term Impact of Sotatercept on Morbidity and Mortality in Patients with Pulmonary Arterial Hypertension (PAH). McLaughlin, V., Alsumali, A., Liu, R., et al.[2023]

SOM230 and KE108, two new somatostatin analogs, show functional selectivity at the sst2A receptor, mimicking some actions of somatostatin while antagonizing others, which may enhance their therapeutic potential for treating tumors.

These analogs exhibit reduced receptor internalization compared to somatostatin due to both decreased phosphorylation at specific sites and phosphorylation-independent mechanisms, suggesting a unique regulatory profile that could improve their efficacy in clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ligand-dependent mechanisms of sst2A receptor trafficking: role of site-specific phosphorylation and receptor activation in the actions of biased somatostatin agonists. Kao, YJ., Ghosh, M., Schonbrunn, A.[2021]

In a phase 3 trial involving 323 adults with pulmonary arterial hypertension, sotatercept significantly improved exercise capacity, as measured by a 34.4 m increase in the 6-minute walk distance compared to just 1.0 m in the placebo group, indicating its efficacy in enhancing physical performance.

Sotatercept also showed significant improvements across multiple secondary endpoints related to pulmonary health, although it was associated with some adverse effects like epistaxis and increased blood pressure, highlighting the need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 3 Trial of Sotatercept for Treatment of Pulmonary Arterial Hypertension. Hoeper, MM., Badesch, DB., Ghofrani, HA., et al.[2023]

The Phase 3 STELLAR trial demonstrated that sotatercept significantly improves exercise capacity and reduces pulmonary vascular resistance in patients with pulmonary arterial hypertension, indicating its efficacy as a treatment option.

The study involved a large cohort of patients, providing robust evidence for the safety and effectiveness of sotatercept in managing this serious condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In symptomatic PAH, adding sotatercept to stable background therapy improved 6-min walk distance at 24 wk. Estrada, RA.[2023]

Cytotoxic somatostatin analogs, specifically paclitaxel-octreotide (PTX-OCT) and 2paclitaxel-octreotide (2PTX-OCT), effectively target non-small cell lung cancer (NSCLC) cells expressing somatostatin receptors (SSTR) 2 and 5, leading to significant growth inhibition and apoptosis in these cancer cells.

These PTX-OCT conjugates show promise in overcoming paclitaxel resistance, as they induce lower levels of the MDR-1 gene associated with drug resistance, making them a potentially safer and more effective treatment option for NSCLC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted paclitaxel-octreotide conjugates inhibited the growth of paclitaxel-resistant human non-small cell lung cancer A549 cells in vitro. Liu, Y., Xia, H., Wang, Y., et al.[2022]

In a 24-week trial involving 106 adults with pulmonary arterial hypertension, sotatercept significantly reduced pulmonary vascular resistance compared to placebo, indicating its efficacy in improving this condition.

Sotatercept also improved exercise capacity, as shown by a greater increase in 6-minute walk distance in the treatment groups, although some hematologic adverse events were noted, including thrombocytopenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sotatercept for the Treatment of Pulmonary Arterial Hypertension. Humbert, M., McLaughlin, V., Gibbs, JSR., et al.[2021]

Pasireotide, a multireceptor-targeted somatostatin analog, shows promise in reducing systemic IGF-1 levels more effectively than existing somatostatin analogs, which may enhance its antitumor effects.

The mechanism of action for pasireotide includes both direct inhibition of tumor growth through apoptosis and indirect effects by suppressing growth factors and hormones, making it a potentially effective treatment for solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Somatostatin receptors in non-neuroendocrine malignancies: the potential role of somatostatin analogs in solid tumors. Hasskarl, J., Kaufmann, M., Schmid, HA.[2014]

Citations

1. merck.com merck.com/news/u-s-fda-approves-updated-indication-for-winrevair-sotatercept-csrk-in-adults-with-pulmonary-arterial-hypertension-pah-who-group-1-pulmonary-hypertension-based-on-phase-3-zenith-study/

U.S. FDA Approves Updated Indication for WINREVAIR ... Adding WINREVAIR to background PAH therapy improved exercise capacity and WHO functional class (FC), and reduced the risk of clinical ...

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

Phase 3 Trial of Sotatercept for Treatment of Pulmonary ... In the phase 3 STELLAR trial, we further investigated the efficacy, safety, and adverse-event profile of sotatercept in combination with stable background ...

3. 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 ...

4. winrevair.com winrevair.com/clinical-trials-results/

Clinical Trial Results for WINREVAIR™ (sotatercept-csrk) WINREVAIR could improve important measures of heart health and function that help your doctor monitor your PAH. In STELLAR, adults with PAH who added WINREVAIR ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03496207

NCT03496207 | A Study of Sotatercept for the Treatment ... Study A011-09 is designed to assesses the efficacy and safety of sotatercept (ACE-011) relative to placebo in adults with pulmonary arterial hypertension (PAH).

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06925750

NCT06925750 | A Clinical Study of Sotatercept (MK-7962) ... A past study, MK-7962-024 (LIGHTRAY) (NCT06664801), learned about the safety and effects of sotatercept in people with PAH. One of the goals of that study was ...

7. 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.