Sotatercept for Pulmonary Hypertension

(HARMONIZE Trial)

Recruiting at 46 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Merck Sharp & Dohme LLC

Disqualifiers: Pulmonary hypertension, Liver disease, Pregnancy, 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

Compensation: Varies

Number of Visits: 3

Duration: 168 weeks

130 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates a new treatment for a specific type of pulmonary hypertension, which is high blood pressure in the lungs caused by heart problems. The treatment, sotatercept, is being tested for long-term safety and effectiveness. Participants will receive sotatercept in one of two doses and will be monitored for safety for up to 168 weeks. Individuals who participated in a previous sotatercept study and completed it without discontinuing treatment may be eligible for this trial. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

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

Research has shown that sotatercept has been well-tolerated in past studies for treating pulmonary hypertension, which is high blood pressure in the lungs. The treatment maintains a good safety record. Common side effects include increased hemoglobin levels (a protein in red blood cells), reduced platelet counts (cells that help blood clot), and mild skin changes like small, visible blood vessels. These side effects are typically mild and short-lived.

Additionally, sotatercept has been associated with a reduced risk of serious health issues. Studies indicate a decrease in deaths from any cause and a lower risk of right ventricular failure, a type of heart problem. Overall, participants have handled sotatercept well in clinical settings, which is encouraging for those considering joining the study. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for pulmonary hypertension?

Researchers are excited about sotatercept for pulmonary hypertension because it offers a novel approach by targeting the underlying causes of the disease. Unlike standard treatments that primarily focus on dilating blood vessels to reduce pressure, sotatercept works by blocking certain proteins that contribute to blood vessel remodeling and increased pressure in the lungs. This unique mechanism could potentially lead to more effective management of pulmonary hypertension and improve long-term outcomes for patients. Additionally, sotatercept is administered as a subcutaneous injection every three weeks, which might be more convenient for patients compared to some existing therapies that require daily administration.

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

Studies have shown that sotatercept can effectively treat pulmonary arterial hypertension, a type of high blood pressure affecting the lungs. Research indicates that sotatercept improves heart function and physical performance in patients. Specifically, patients have shown improvements in the distance walked in six minutes and lower levels of a heart stress marker. Additionally, the treatment has reduced the pressure the heart must overcome to pump blood through the lungs. These improvements have persisted over time, suggesting sotatercept could benefit those with pulmonary hypertension linked to heart failure with preserved ejection fraction (HFpEF). While side effects are relatively rare, an increase in hemoglobin levels, a protein in red blood cells, has been noted. Participants in this trial will receive either 0.7 mg/kg or 0.3 mg/kg of sotatercept as a subcutaneous injection every three weeks. ^{6 7 8 9 10}

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 people with a specific kind of pulmonary hypertension called Cpc-PH, which results from heart failure with preserved ejection fraction (HFpEF). Only those who completed the CADENCE study without stopping the treatment and can safely join the HARMONIZE extension are eligible.

Inclusion Criteria

I finished the CADENCE study without stopping the treatment and can safely join the HARMONIZE study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive sotatercept 0.3 mg/kg or 0.7 mg/kg subcutaneous injection every 3 weeks

168 weeks

Injections every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

19 weeks

Open-label extension

Participants continue to receive sotatercept to evaluate long-term safety and tolerability

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Sotatercept

Trial Overview The trial is testing Sotatercept's long-term safety and tolerability in treating Cpc-PH caused by HFpEF. It's an extension study, meaning it continues to follow participants from a previous sotatercept study over a longer period.

How Is the Trial Designed?

Group I: Sotatercept 0.7 mg/kg Experimental Treatment 1 Intervention

Participants receive sotatercept 0.7 mg/kg SC injection Q3W for up to approximately 168 weeks or until discontinuation.

Group II: Sotatercept 0.3 mg/kg Experimental Treatment 1 Intervention

Participants receive sotatercept 0.3 mg/kg subcutaneous (SC) injection every 3 weeks (Q3W) for up to approximately 168 weeks or until discontinuation.

Who Is Running the Clinical Trial?

Merck Sharp & Dohme LLC

Lead 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

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]

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]

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 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. 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. 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 ...

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. publications.ersnet.org publications.ersnet.org/content/erj/66/1/2401435

A long-term follow-up study of sotatercept for treatment of ... Improvements in 6MWD, NT-proBNP, WHO Functional Class and SFRS achieved from baseline of SOTERIA were largely maintained at 1 year, including in ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1053249824018746

Sotatercept for the treatment of pulmonary arterial ... The primary endpoint of the phase 2 PULSAR trial was a change in PVR.9, 36 Compared to placebo, there was a change in PVR of −1.8 WU (95% CI, −3.0 to −0.6; p = ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S153718912500059X

Clinical outcomes and safety of sotatercept in pulmonary ... Sotatercept significantly improves functional and hemodynamic outcomes in PAH, with a favorable safety profile. While mortality benefits remain uncertain.

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40668414/

Efficacy and safety of sotatercept in pulmonary arterial ... Also, sotatercept decreased all-cause mortality (RR = 0.46; 95% CI 0.22-0.98) and right ventricular failure (RR = 0.26; 95% CI 0.09-0.75); ...

8. 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 ...

9. acc.org acc.org/Latest-in-Cardiology/Articles/2025/11/01/01/Cover-Story-Pulmonary-Hypertension

Cover Story | Pulmonary Hypertension: Bridging the Gap ... At a median follow-up of 10.6 months, sotatercept reduced the relative risk of major morbidity and mortality events by 76% compared to placebo ( ...

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

Sotatercept in pulmonary arterial hypertension: revolution, risk ... The main safety signals observed in clinical trials are increased haemoglobin, decreased platelet counts, telangiectasia, and – mostly mild and self-limiting – ...