Sotatercept for Pulmonary Arterial Hypertension

(HYPERION Trial)

No longer recruiting at 241 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Acceleron Pharma Inc.

Must be taking: PAH therapies

Must not be taking: Intravenous inotropes

Disqualifiers: Hypertension, HIV, Hepatitis, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 36 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, sotatercept, for individuals with pulmonary arterial hypertension (PAH). PAH narrows the arteries in the lungs, leading to high blood pressure in these vessels, causing shortness of breath and fatigue. The study aims to determine if sotatercept, combined with standard PAH treatments, can delay disease progression compared to a placebo. It is suitable for those diagnosed with PAH within the last year, at intermediate or high risk of worsening, and already on stable treatments. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Do I need to stop my current medications to join the trial?

The trial does not specify that you need to stop your current medications. In fact, participants must be on stable doses of a double or triple combination of background PAH therapies and diuretics for at least 90 days prior to screening. However, you should discuss your specific medications with the trial team to ensure they are compatible with the study requirements.

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 stable doses of your current PAH therapies and diuretics for at least 90 days before joining the study.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that sotatercept, when added to standard treatment for pulmonary arterial hypertension (PAH), is generally well-tolerated by patients. Studies, including long-term follow-ups, indicate that patients taking sotatercept did not experience more serious side effects than expected.

In a trial, an independent committee reviewed the safety data and found it acceptable. The most common side effects were mild, such as headaches and reactions at the injection site. These findings suggest that sotatercept is relatively safe to use with PAH treatments, although individual experiences may vary. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for pulmonary arterial hypertension?

Most treatments for pulmonary arterial hypertension (PAH), like endothelin receptor antagonists or phosphodiesterase-5 inhibitors, aim to manage symptoms by dilating blood vessels or reducing blood pressure. But Sotatercept works differently, targeting a specific biological pathway known as the transforming growth factor-beta (TGF-β) superfamily, which plays a role in vascular remodeling. Researchers are excited about Sotatercept because it offers a novel approach to treating PAH, potentially addressing the root cause of the disease rather than just alleviating symptoms. This could lead to improved outcomes for patients by slowing or even reversing disease progression.

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

Research has shown that sotatercept can help people with pulmonary arterial hypertension (PAH) by improving exercise capacity and slowing the progression of their condition. In this trial, some participants will receive sotatercept alongside their existing PAH treatments, potentially supporting better heart health and function. Specifically, patients in previous studies found it easier to exercise and faced a lower risk of their condition worsening. Sotatercept has also been beneficial for those recently diagnosed with PAH. These findings suggest that sotatercept could be an effective option for managing PAH. ^{1 4 5 6 7}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

This trial is for adults over 18 with newly diagnosed Pulmonary Arterial Hypertension (PAH) who are at intermediate or high risk of disease progression. They must be able to walk a certain distance and adhere to the study's schedule. Women of childbearing age and men must follow strict contraception guidelines.

Inclusion Criteria

You have a higher risk of complications related to pulmonary hypertension based on certain scoring systems.

Ability to adhere to study visit schedule and understand and comply with all protocol requirements

I have had a heart cath test showing specific heart and lung pressures, indicating a certain type of high blood pressure in my lung arteries.

Exclusion Criteria

Pregnant or breastfeeding women

Your heart's electrical activity shows a specific pattern that may not be safe for the study.

I have a history of certain medical conditions or surgeries.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive sotatercept or placebo plus background PAH therapy administered subcutaneously every 21 days

Up to 36 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term in the MK-7962-004 extension study or by commercial access

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Sotatercept

Trial Overview The trial tests if Sotatercept, on top of standard PAH therapy, can delay the worsening of PAH symptoms compared to a placebo. Participants will either receive Sotatercept or a placebo alongside their regular treatment for PAH.

How Is the Trial Designed?

Group I: Sotatercept plus background PAH therapy Experimental Treatment 1 Intervention

Administered at a starting dose of 0.3 mg/kg, with a target dose of 0.7 mg/kg, subcutaneously (SC) every 21 days plus background PAH therapy

Group II: Placebo plus background PAH therapy Placebo Group 1 Intervention

Administered subcutaneously (SC) every 21 days plus background PAH therapy

Who Is Running the Clinical Trial?

Acceleron Pharma Inc.

Lead Sponsor

Trials

27

Recruited

3,100+

Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA

Lead Sponsor

Trials

33

Recruited

4,300+

Acceleron Pharma Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)

Lead Sponsor

Trials

33

Recruited

4,300+

Published Research Related to This Trial

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]

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 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]

In the phase 3 STELLAR trial, sotatercept significantly improved key hemodynamic parameters in patients with pulmonary arterial hypertension (PAH), including a reduction in mean pulmonary artery pressure by 13.9 mmHg and pulmonary vascular resistance by 254.8 dyn·s·cm-5, indicating enhanced right heart function.

Sotatercept also showed improvements in right ventricular work and power, as well as echocardiographic measures of right heart function, suggesting it may be an effective treatment option for managing PAH in pre-treated patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of sotatercept on haemodynamics and right heart function: analysis of the STELLAR trial. Souza, R., Badesch, DB., Ghofrani, HA., et al.[2023]

Pulmonary hypertension (PH) is a serious complication of connective tissue diseases (CTD), particularly prevalent in systemic scleroderma, and is associated with a poor prognosis, highlighting the importance of early diagnosis.

Current treatments for PAH-CTD include various classes of medications such as prostacyclin derivatives, nitric oxide stimulators, and endothelin receptor antagonists, with ongoing research into new therapies like sotatercept, which may improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent Advances in the Treatment of Pulmonary Arterial Hypertension Associated with Connective Tissue Diseases. Smukowska-Gorynia, A., Gościniak, W., Woźniak, P., 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]

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]

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. 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 ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40167274/

Sotatercept in Patients with Pulmonary Arterial ... Sotatercept improves exercise capacity and delays the time to clinical worsening in patients with World Health Organization (WHO) functional class II or III ...

4. 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 ...

5. 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. Pulmonary arterial ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT07218029

A Clinical Study of Sotatercept (MK-7962) in People With ... The goal of this study is to learn about the long-term safety of sotatercept and if people tolerate it when taken with standard PAH treatment ...

7. 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 ...