What side effects are associated with this type of intervention?

Common treatments for Pulmonary Hypertension, including endothelin receptor antagonists (ERAs) like bosentan and ambrisentan, phosphodiesterase-5 inhibitors (PDE5Is) like sildenafil, and soluble guanylate cyclase stimulators like riociguat, have several known side effects. ERAs can cause hepatotoxicity and peripheral edema. PDE5Is are associated with headaches, flushing, and potential worsening of right heart failure in certain conditions. Soluble guanylate cyclase stimulators may lead to hypotension and gastrointestinal issues. These side effects should be carefully monitored by healthcare providers.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of Pulmonary Hypertension (PH), including endothelin receptor antagonists (ERAs) like ambrisentan, bosentan, and macitentan, which block the actions of endothelin-1, a potent vasoconstrictor. Phosphodiesterase-5 inhibitors (PDE5Is) such as sildenafil and tadalafil increase intracellular cGMP, leading to vasodilation. Soluble guanylate cyclase stimulators like riociguat also enhance cGMP production. These treatments aim to improve exercise capacity, functional status, and hemodynamics in PH patients. While Sotatercept, an Activin Receptor Type IIA Ligand Trap, is still under investigation, it represents a novel approach by targeting different molecular pathways involved in PH.

What other types of research exist?

Promising novel alternatives to Sotatercept for Pulmonary Hypertension patients include: 1) Inhaled Fasudil, a Rho-kinase inhibitor, which has shown acute vasodilator effects in PAH patients. 2) Macitentan, an endothelin receptor antagonist, which has demonstrated efficacy in delaying disease progression and improving exercise tolerance. 3) Oral Treprostinil, a prostacyclin analog, which has shown improvements in dyspnea and exercise capacity when added to other oral agents.

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Sotatercept for Pulmonary Hypertension (CADENCE Trial)

Phase 2

Recruiting

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

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Participants must be aged between 18 to 85 years

Ability to understand and provide documented consent for participation

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from week 24 to week 48 of the extension period

Awards & highlights

CADENCE Trial Summary

This trial will enroll approximately 300 participants who will be randomized 1:1 to receive either sotatercept or placebo.

Who is the study for?

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.Check my eligibility

What is being tested?

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.See study design

What are the potential side effects?

Potential side effects of Sotatercept may include headache, respiratory tract infection, joint pain, nausea or vomiting. The exact side effects will be monitored throughout the trial.

CADENCE Trial Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am between 18 and 85 years old.

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I can understand and agree to participate in the study.

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I agree to use contraception and not donate blood or sperm.

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My heart pumps well, with an ejection fraction of 50% or higher, and it has never been below 45%.

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My heart and lung tests show specific pressures and I can walk at least 100 meters.

CADENCE Trial Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from week 24 to week 48 of the extension period

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from week 24 to week 48 of the extension period

This trial's timeline: 3 weeks for screening, Varies for treatment, and from week 24 to week 48 of the extension period for reporting.

Treatment Details

Study Objectives

Outcome measures can provide a clearer picture of what you can expect from a treatment.

Primary outcome measures

Change From Baseline in Pulmonary Vascular Resistance (PVR) at Week 24

Secondary outcome measures

Change From Baseline in E/e' (Early Mitral Inflow Velocity E and Mitral Annular Early Diastolic Velocity e') Ratio at Week 48

Change From Baseline in Isovolumic Relaxation Time (IVRT) at Week 24

Change From Baseline in Isovolumic Relaxation Time (IVRT) at Week 48

+29 more

CADENCE Trial Design

5Treatment groups

Experimental Treatment

Placebo Group

Group I: Sotatercept 0.3 mg/kg, escalating to 0.7 mg.kgExperimental Treatment1 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/kgExperimental Treatment1 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. After completion of the placebo-controlled treatment period, participants will continue to receive sotatercept SC at a dose level of 0.3 mg/kg Q3W in an extension period for up to 18 months.

Group III: Extension Period: Placebo Crossed Over to Sotatercept 0.3 mg/kg, escalating to 0.7 mg.kgExperimental Treatment1 Intervention

After the placebo-controlled treatment period, placebo participants will cross over to receive 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 then Q3W for up to 18 months in an extension period.

Group IV: Extension Period: Placebo Crossed Over to Sotatercept 0.3 mg/kgExperimental Treatment1 Intervention

After the placebo-controlled treatment period, placebo participants will cross over to receive sotatercept SC at a dose of 0.3 mg/kg Q3W for up to 18 months in an extension period.

Group V: PlaceboPlacebo Group1 Intervention

Delivered subcutaneously (SC) every 3 weeks (Q3W) for 24 weeks in the placebo-controlled treatment period. After completion of the placebo-controlled treatment period, placebo participants will enter into 1 of the 2 sotatercept dose groups in an extension period.

0 / 5Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Pulmonary Hypertension (PH) primarily focus on pulmonary vasodilation and reducing vascular resistance. Phosphodiesterase type 5 (PDE5) inhibitors, such as sildenafil, increase cyclic guanosine monophosphate (cGMP) levels, leading to vasodilation and improved blood flow. Endothelin receptor antagonists (ERAs), like bosentan, block endothelin-1, a potent vasoconstrictor, thereby reducing vascular resistance. Prostacyclin analogs, such as treprostinil, mimic the effects of prostacyclin, promoting vasodilation and inhibiting platelet aggregation. These treatments are crucial for PH patients as they alleviate symptoms and improve exercise capacity. Sotatercept, an investigational drug, differs by targeting the underlying mechanisms of pulmonary vascular remodeling, potentially offering a novel approach to treating PH by addressing the root cause of vascular changes.

Management of Pulmonary Arterial Hypertension.