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

Must not have

Body mass index ≥50 kg/m2, untreated or severe obstructive sleep apnea, and any non-cardiopulmonary conditions limiting the ability to perform 6MWT

Diagnosis of PH in WHO Group 1, 3, 4, or 5

Timeline

Screening 3 weeks

Treatment Varies

Follow Up week 24

Summary

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.

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.

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.

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.

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.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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

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I have been diagnosed with pulmonary hypertension.

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I have a serious lung condition like COPD or interstitial lung disease.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ week 24

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~week 24

This trial's timeline: 3 weeks for screening, Varies for treatment, and week 24 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

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

Secondary study objectives

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

Change From Baseline in Left Ventricular Ejection Fraction (LVEF) at Week 24

Change From Baseline in Mean Pulmonary Arterial Pressure (mPAP) at Week 24

+10 more

Trial Design

3Treatment 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.

Group III: PlaceboPlacebo Group1 Intervention

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

0 / 8Eligibility 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.