Sotatercept for Pulmonary Hypertension

(CADENCE Trial)

Recruiting in Palo Alto (17 mi)

+143 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

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

Trial Summary

What is the purpose of this trial?

This trial tests sotatercept, a medication aimed at improving heart and lung function in adults with a specific type of heart failure. It works by reducing resistance in lung blood vessels, helping the heart pump blood more easily.

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 sotatercept safe for humans?

Sotatercept has been studied in people with pulmonary arterial hypertension, and safety data from these studies show that it is generally safe, with no significant differences in safety between those who developed antibodies to the drug and those who did not. ^{1 2 3 4 5}

What makes the drug Sotatercept unique for treating pulmonary hypertension?

Sotatercept is unique because it works by targeting specific pathways involved in blood vessel function, which is different from other treatments that primarily focus on dilating blood vessels. This novel mechanism may offer new hope for patients with pulmonary hypertension, a condition with limited treatment options. ^{6 7 8 9 10}

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

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 between 18 and 85 years old.

I am following the required pregnancy prevention measures.

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.

Trial Timeline

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

Treatment Details

Interventions

• Placebo (Drug)
• Sotatercept (Other)

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

References

1. 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]

2. England pubmed.ncbi.nlm.nih.gov

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

3. 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]

4. United States 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. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Recent Advances in the Treatment of Pulmonary Arterial Hypertension Associated with Connective Tissue Diseases. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Somatostatin, its receptors and analogs, in lung cancer. [2017]

7. Germany pubmed.ncbi.nlm.nih.gov

Beta(2)/beta(3)-di- and alpha/beta(3)-tetrapeptide derivatives as potent agonists at somatostatin sst(4) receptors. [2018]

8. Singapore 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. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Inhibition of endothelial proliferation by the somatostatin analogue SOM230. [2018]

10. Czech Republic pubmed.ncbi.nlm.nih.gov

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