Sotatercept for Pulmonary Hypertension

(HARMONIZE Trial)

Recruiting at 6 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

Trial Summary

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.

What data supports the effectiveness of the drug Sotatercept for treating pulmonary hypertension?

Research shows that adding Sotatercept to existing treatments for pulmonary arterial hypertension (a type of high blood pressure affecting the lungs) improved patients' ability to walk further in six minutes after 24 weeks. Additionally, it significantly reduced the resistance in blood vessels in the lungs, indicating better blood flow. ^{1 2 3 4 5}

How is the drug sotatercept different from other treatments for pulmonary hypertension?

Sotatercept is unique because it is a fusion protein that works by trapping activins and growth differentiation factors, aiming to restore balance in signaling pathways involved in pulmonary arterial hypertension. This mechanism is different from other treatments, which typically focus on dilating blood vessels or reducing blood pressure. ^{1 2 3 4 5}

What is the purpose of this trial?

Researchers are looking for new ways to treat people with a type of pulmonary hypertension called combined postcapillary and precapillary pulmonary hypertension (Cpc-PH). This study focuses on Cpc-PH that is caused by heart failure with preserved ejection fraction (HFpEF). Researchers want to know if the study treatment, sotatercept, can treat people with Cpc-PH caused by HFpEF. This is an extension study, which means people who took part in a certain study on sotatercept for Cpc-PH (called a parent study) may be able to join this study. In this extension study, people will take sotatercept and researchers will follow their health for a longer time. The main goal of this extension study is to learn about the long-term safety of sotatercept and if people tolerate it over a longer period of time.

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

References

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

Phase 3 Trial of Sotatercept for Treatment of Pulmonary Arterial Hypertension. [2023]

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

Sotatercept for the Treatment of Pulmonary Arterial Hypertension. [2021]

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

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

4. England pubmed.ncbi.nlm.nih.gov

Sotatercept for the treatment of pulmonary arterial hypertension: PULSAR open-label extension. [2023]

5. United States 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). [2023]