Sotatercept for Pulmonary Hypertension

(CADENCE Trial)

Not currently recruiting at 155 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 2

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

Must not be taking: PAH-specific therapies

Disqualifiers: PH WHO Group 1, lung disease, cardiovascular, others

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

Compensation: Varies

Number of Visits: 8

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called sotatercept for individuals with pulmonary hypertension, a type of high blood pressure in the lungs linked to heart failure with preserved ejection fraction. The researchers aim to determine if sotatercept can lower lung blood pressure and improve exercise ability, measured by walking distance. Participants will receive either sotatercept or a placebo (a substance with no active treatment) to compare results. Ideal candidates have stable heart failure and can walk at least 100 meters in six minutes. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important medical advancements.

Will I have to stop taking my current medications?

The trial requires that your current medications for heart failure or other conditions be stable for at least 30 days before starting the study. However, diuretics and anticoagulants can be adjusted as needed, but not within 7 days of starting the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that sotatercept has been tested in people with pulmonary arterial hypertension (PAH), a condition similar to the focus of this trial. Patients who took sotatercept improved over time, and no deaths occurred compared to those who took a placebo. In another study, patients on sotatercept experienced fewer serious issues, such as hospitalizations or heart problems, than those who did not take the drug. These results suggest that sotatercept is generally well-tolerated. However, since this clinical trial is in the early stages, the researchers are still collecting safety information. Existing data suggests it might be safe for use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Sotatercept is unique because it represents a new approach to treating pulmonary hypertension. Unlike standard treatments that often focus on dilating blood vessels, Sotatercept works by targeting a different pathway in the body, specifically the transforming growth factor-beta (TGF-β) superfamily, which plays a role in blood vessel remodeling. This new mechanism of action could potentially address the underlying disease process more effectively. Researchers are excited about its potential to improve outcomes for patients with pulmonary hypertension by offering a novel therapeutic option that goes beyond simply managing symptoms.

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

Research has shown that sotatercept yields promising results for treating pulmonary arterial hypertension (PAH). In earlier studies, it improved patients' exercise capacity and reduced the risk of their condition worsening. Sotatercept affects certain proteins in blood vessels, helping them relax and widen, which enhances blood flow. In this trial, participants will receive either sotatercept at varying dosages or a placebo. Researchers hope that sotatercept could also benefit individuals with Cpc-PH due to HFpEF, a condition where the heart struggles to pump blood efficiently. Although this treatment remains under study, early results in similar conditions are encouraging. ^{1 2 3 6 7}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

Adults aged 18-85 with Cpc-PH due to HFpEF, stable on heart failure medications for at least 30 days, and able to perform a six-minute walk test. Participants must not have severe lung disease, liver disease, recent major surgery or other significant health issues that could interfere with the study.

Inclusion Criteria

Agreement to not participate in any other trials of investigational drugs/devices while enrolled in the study

I am following the required pregnancy prevention measures.

I can understand and agree to participate in the study.

Exclusion Criteria

I have a BMI of 50 or more, severe sleep apnea, and conditions that prevent me from walking.

I don't have a history of specific heart conditions, major surgeries, chronic liver disease, or recent drug trials.

I have heart-related health issues.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment

Participants receive either sotatercept or placebo subcutaneously every 3 weeks for 24 weeks

24 weeks

8 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

Extension

Participants who completed the treatment period may be eligible for an extension study

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Sotatercept

Trial Overview

The trial is testing Sotatercept's effectiveness in improving pulmonary vascular resistance and exercise capacity compared to placebo in patients with high blood pressure-related pulmonary hypertension caused by heart failure with preserved ejection fraction.

How Is the Trial Designed?

Group I: Sotatercept 0.3 mg/kg, escalating to 0.7 mg.kg Experimental Treatment 1 Intervention

Sotatercept SC at a starting dose level of 0.3 mg/kg for 3 dosing visits (Q3W), then escalating to 0.7 mg/kg SC on the fourth dosing visit and Q3W for the remainder of the 24-week treatment Period.

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

Participants will receive sotatercept SC at a dose level of 0.3 mg/kg Q3W for 24 weeks in the placebo-controlled treatment period.

Group III: Placebo Placebo Group 1 Intervention

Delivered subcutaneously (SC) every 3 weeks (Q3W) for 24 weeks in the placebo-controlled treatment period.

Who Is Running the Clinical Trial?

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+

Acceleron Pharma Inc.

Lead Sponsor

Trials

27

Recruited

3,100+

Published Research Related to This Trial

In a phase III trial involving 162 participants with pulmonary arterial hypertension (PAH), sotatercept demonstrated a 25.9% incidence of antidrug antibodies (ADAs), but this did not significantly impact the drug's pharmacokinetics, efficacy, or safety.

Sotatercept was found to be effective in improving key measures of PAH, such as the 6-minute walk distance and pulmonary vascular resistance, regardless of ADA status, indicating its robust therapeutic potential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Impact of Immunogenicity on the Pharmacokinetics, Efficacy, and Safety of Sotatercept in a Phase III Study of Pulmonary Arterial Hypertension. Liao, K., Mackenzie, H., Ait-Oudhia, S., et al.[2023]

Lanreotide, a somatostatin analog, has been shown to significantly prolong progression-free survival in patients with metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs), with a median survival of 32.8 months compared to 18 months for placebo, based on the CLARINET study.

The CLARINET study provides strong evidence for the antiproliferative effects of lanreotide, leading to its recommendation for early treatment in patients with well-differentiated metastatic grade 1 and grade 2 GEP-NETs, regardless of the primary tumor location.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Antiproliferative Effect of Somatostatin Analogs - Data Analyses and Clinical Applications in the Context of the CLARINET Study]. Bencsiková, B.[2022]

Somatostatin and its analogs, such as octreotide and somatuline, have shown potential in inhibiting the growth of lung tumors, including those that do not express somatostatin receptors, indicating a broad mechanism of action.

These somatostatin analogs may also enhance the effectiveness of chemotherapy in treating lung cancer, suggesting they could be a valuable addition to current treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Somatostatin, its receptors and analogs, in lung cancer. O'Byrne, KJ., Schally, AV., Thomas, A., et al.[2017]

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]

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]

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 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]

SOM230, a new somatostatin analogue, significantly inhibits the proliferation of human umbilical vein endothelial cells (HUVECs) by up to 46% at certain concentrations, while Octreotide does not have this effect.

HUVECs express specific somatostatin receptors (SSTRs 1, 2, and 5), which suggests that SOM230's mechanism of action may involve these receptors, making it a promising candidate for antiangiogenic therapy in treating neuroendocrine tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of endothelial proliferation by the somatostatin analogue SOM230. Adams, RL., Adams, IP., Lindow, SW., et al.[2018]

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]

Four linear beta(2)/beta(3)-di- and alpha/beta(3)-tetrapeptides were found to selectively bind to human somatostatin sst(4) receptors with strong affinity, indicating their potential as effective agonists.

These peptides demonstrated significant agonist activity in inhibiting adenylate cyclase and stimulating luciferase expression, suggesting they could be useful for further research into sst(4) receptor functions and may have therapeutic applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beta(2)/beta(3)-di- and alpha/beta(3)-tetrapeptide derivatives as potent agonists at somatostatin sst(4) receptors. Nunn, C., Rueping, M., Langenegger, D., et al.[2018]

Citations

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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 ...

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ncbi.nlm.nih.gov

ncbi.nlm.nih.gov/books/NBK612745/

Clinical Review - Sotatercept (Winrevair) - NCBI Bookshelf - NIH

CDA-AMC received a submission from the Pulmonary Hypertension Association of Canada (PHA Canada), which included patient and caregiver survey data and insights.

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nejm.org/doi/full/10.1056/NEJMoa2213558

Phase 3 Trial of Sotatercept for Treatment of Pulmonary ...

Unless otherwise specified, we report the main results from the first 24 weeks of treatment for all efficacy and safety variables. The results of the analysis ...

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clinicaltrials.gov

clinicaltrials.gov/study/NCT07218029

A Clinical Study of Sotatercept (MK-7962) in People With ...

Researchers are looking for more ways to treat PAH. In PAH, the blood vessels in the lungs become thick and narrow, which makes it harder ...

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merck.com

merck.com/news/merck-announces-phase-3-hyperion-study-of-winrevair-sotatercept-csrk-met-primary-endpoint-in-recently-diagnosed-adults-with-pulmonary-arterial-hypertension-pah/

Merck Announces Phase 3 HYPERION Study of ...

WINREVAIR significantly reduced the risk of clinical worsening events in recently diagnosed PAH patients over 70 percent of whom were on double background ...

6.

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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).

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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.