What side effects are associated with this type of intervention?

Common treatments for Pulmonary Arterial Hypertension (PAH) include endothelin receptor antagonists (ERAs) like bosentan and ambrisentan, phosphodiesterase-5 inhibitors (PDE5Is) such as sildenafil, and prostacyclin receptor agonists like selexipag. Known side effects of ERAs include hepatotoxicity and peripheral edema. PDE5Is can cause headaches, flushing, and potential hypotension. Prostacyclin receptor agonists may lead to headaches, nausea, vomiting, diarrhea, flushing, and jaw pain. These side effects are important considerations when evaluating treatment options for PAH.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of Pulmonary Arterial Hypertension (PAH). These include Endothelin Receptor Antagonists (ERAs) such as bosentan, ambrisentan, and macitentan, which work by blocking the effects of endothelin-1, a potent vasoconstrictor. Phosphodiesterase-5 inhibitors (PDE5Is) like sildenafil and tadalafil increase intracellular cGMP to promote vasodilation. Additionally, Riociguat, a soluble guanylate cyclase stimulator, has been approved for its role in increasing cGMP levels. Prostacyclin analogs and receptor agonists, such as epoprostenol, treprostinil, and selexipag, are also used to manage PAH by mimicking the effects of prostacyclin, a vasodilator. These treatments aim to improve exercise capacity, functional class, and delay disease progression in PAH patients.

What other types of research exist?

Promising alternatives to Sotatercept for PAH treatment include: <ol> <li>Macitentan: An endothelin receptor antagonist that has shown efficacy in delaying disease progression and improving exercise tolerance.</li> <li>Selexipag: An oral prostacyclin receptor agonist that has demonstrated benefits in improving time to clinical worsening.</li> <li>Treprostinil: An oral prostanoid that has shown improvements in dyspnea and exercise capacity, though with notable side effects.</li> <li>Fasudil (AT-877ER): A Rho-kinase inhibitor that has shown clinical benefits in mid-term treatment of PAH.</li> </ol>

← Back to Search

Other

Sotatercept for Pulmonary Arterial Hypertension (HYPERION Trial)

Phase 3

Recruiting

Research Sponsored by Acceleron Pharma Inc.

Eligibility Criteria Checklist

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

Must have

Documented diagnostic right heart catheterization (RHC) within 12 months of screening documenting a minimum PVR of ≥ 4 Wood units and pulmonary capillary wedge pressure (PCWP) or left ventricular end-diastolic pressure (LVEDP) of ≤ 15 mmHg, with the diagnosis of WHO PAH Group 1 in specific subtypes

Age ≥ 18 years

Must not have

Uncontrolled systemic hypertension as evidenced by sitting systolic blood pressure (BP) > 180 mmHg or sitting diastolic BP > 110 mmHg during the Screening Visit after a period of rest

Hemoglobin at screening above gender-specific upper limit of normal (ULN), per local laboratory test

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to ~46 months

Awards & highlights

Pivotal Trial

Summary

This trial is testing sotatercept, a new medication, to see if it can help people with a specific type of high blood pressure in the lungs (PAH) when added to their usual treatment. The study focuses on patients who are newly diagnosed and at higher risk of their condition worsening. Sotatercept aims to reduce the pressure in the lung's blood vessels, potentially slowing down disease progression. Sotatercept has shown significant reduction in pulmonary vascular resistance and maintained clinical efficacy in previous studies.

Who is the study for?

This trial is for adults over 18 with newly diagnosed Pulmonary Arterial Hypertension (PAH) who are at intermediate or high risk of disease progression. They must be able to walk a certain distance and adhere to the study's schedule. Women of childbearing age and men must follow strict contraception guidelines.

What is being tested?

The trial tests if Sotatercept, on top of standard PAH therapy, can delay the worsening of PAH symptoms compared to a placebo. Participants will either receive Sotatercept or a placebo alongside their regular treatment for PAH.

What are the potential side effects?

While specific side effects for Sotatercept in this context aren't detailed here, similar medications may cause issues like blood pressure changes, fatigue, headache, gastrointestinal discomforts, and potential risks during pregnancy.

Eligibility Criteria

Inclusion Criteria

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

Select...

I have had a heart cath test showing specific heart and lung pressures, indicating a certain type of high blood pressure in my lung arteries.

Select...

I am 18 years old or older.

Select...

My pulmonary arterial hypertension is moderate to severe.

Exclusion Criteria

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

Select...

My blood pressure is not higher than 180/110 mmHg.

Select...

My hemoglobin level is above the normal range for my gender.

Select...

I have been diagnosed with a specific type of high blood pressure in my lungs.

Select...

I have been diagnosed with a specific type of pulmonary arterial hypertension.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to ~46 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to ~46 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to ~46 months for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Time to Clinical Worsening

Secondary study objectives

Change from Baseline in 6MWD

Change from Baseline in NT-proBNP Levels

Change from Baseline in the Cardiopulmonary Symptoms Domain Score of PAH-SYMPACT®

+9 more

Side effects data

From 2022 Phase 3 trial • 324 Patients • NCT04576988

20%

Headache

15%

COVID-19

12%

Diarrhoea

12%

Epistaxis

10%

Telangiectasia

10%

Nausea

10%

Fatigue

10%

Dizziness

Injection site pain

Hypokalaemia

Rash

Flushing

Oedema peripheral

Thrombocytopenia

Nasopharyngitis

Urinary tract infection

Dyspnoea

Fall

Iron deficiency

Pulmonary arterial hypertension

Bronchitis

Inguinal hernia

Atrial flutter

Supraventricular tachycardia

Abdominal pain

Pancreatitis

Cellulitis

Pneumonia

Pneumonia influenzal

Respiratory tract infection

Sepsis

Upper respiratory tract infection

Osteoporotic fracture

Acute kidney injury

Haemoptysis

Pulmonary artery aneurysm

Upper gastrointestinal haemorrhage

Joint injury

Sjogren's syndrome

Cerebral haematoma

Device malfunction

Nephritis

Sarcoidosis

Gastroenteritis viral

100%

80%

60%

40%

20%

Study treatment Arm

Placebo Plus Background PAH Therapy (LTDB Period)

Placebo Plus Background PAH Therapy (DBPC Period)

Sotatercept Plus Background PAH Therapy (DBPC Period)

Sotatercept Plus Background PAH Therapy (LTDB Period)

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: Sotatercept plus background PAH therapyExperimental Treatment1 Intervention

Administered at a starting dose of 0.3 mg/kg, with a target dose of 0.7 mg/kg, subcutaneously (SC) every 21 days plus background PAH therapy

Group II: Placebo plus background PAH therapyPlacebo Group1 Intervention

Administered subcutaneously (SC) every 21 days plus background PAH therapy

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Sotatercept

2019

Completed Phase 3

~690

0 / 7Eligibility 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 Arterial Hypertension (PAH) include endothelin receptor antagonists (ERAs), which block the effects of endothelin-1, a potent vasoconstrictor, thereby reducing blood vessel constriction and lowering blood pressure in the lungs. Phosphodiesterase-5 inhibitors (PDE5Is) work by increasing nitric oxide availability, leading to vasodilation and improved blood flow. Prostacyclin analogs mimic the effects of prostacyclin, a natural vasodilator, and inhibit platelet aggregation, which helps to reduce pulmonary artery pressure. Sotatercept, an investigational drug, acts as an activin receptor type IIA ligand trap, modulating the transforming growth factor-beta (TGF-β) superfamily signaling, which is involved in vascular remodeling and inflammation. These treatments are vital for PAH patients as they target different pathways to alleviate symptoms, improve exercise capacity, and potentially slow disease progression.