SIRIUS - Initial Combination Therapy With an Endothelin Receptor Antagonist, a Phosphodiesterase-5 Inhibitor and Sotatercept in Patients With Newly Diagnosed Pulmonary Arterial Hypertension

NCT07266519 | Not Yet Recruiting Phase 2 DMC

• 2 other identifiers: KKS-3222025-522266-67-00
• Study Type: interventional
• Target: 25
• Locations: 0 countries
• Sites: N/A

Brief Summary

The study aims to see how 24 weeks of triple therapy-an endothelin receptor antagonist (ERA), a phosphodiesterase-5 inhibitor (PDE5i), and sotatercept-affects pulmonary vascular resistance (PVR) in patients with newly diagnosed pulmonary arterial hypertension (PAH). SIRIUS is a 24-week, single-arm, open-label study with up to 42 days of screening and a 28-day safety follow-up. It will enroll 25 patients and will be conducted only in countries where all treatments are available and covered. After 24 weeks, PAH treatment is decided by the doctor.

Conditions

Pulmonary Arterial Hypertension (PAH)

Keywords

triple therapy; PAH; treatment-naiive

Outcome Measures

Primary Outcomes (1)

• Assessment of the effect on pulmonary vascular resistance (PVR)

  Change in PVR from screening at week 24 after 6-months of treatment with triple combination therapy in PAH patients

  24 weeks

Study Arms (1)

Single arm

EXPERIMENTAL

Treatment arm

Drug: Sotatercept 0.3 mg/kg escalating to 0.7 mg/kg; Drug: Sotatercept

Interventions

Sotatercept 0.3 mg/kg escalating to 0.7 mg/kg DRUG

subcutaneously administration in 3-weekly intervals

Single arm

Sotatercept DRUG

Patients are traitment-naiive before start of study. Therapy will be a triple combination therapy with an endothelin receptor antagonist (ERA), a phosphodiesterase-5 inhibitor (PDE5i), and Sotatercept

Single arm

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18- 70 years
• Treatment-naïve patients diagnosed within 12 weeks prior to screening with I/H/D-PAH or PAH associated with corrected congenital heart disease (disease (≥12 months after correction). Patients who have received treatment with PDE5is and/or ERAs for up to 6 weeks after diagnosis are eligible provided that state-of-the-art right heart catheterization has been performed at PAH diagnosis.
• PVR \>5 WU, mPAP ≥35 mmHg and PAWP or LVEDP ≤15 mmHg at PAH diagnosis.
• Signed written informed consent
• Normal blood counts for platelets and erythrocytes
• Women of childbearing potential must be willing to remain abstinent or use adequate and reliable contraception throughout the study and for at least 4 months after the last dose of study medication has been received.
• WOCBP must use one of the following highly effective methods of birth control that result in a low failure rate of less than 1% per year when used consistently and correctly - according to recommendations by the European Heads of Medicines Agencies - from at least 14 days before the first administration of study medication until 4 month after the last administration of study medication:
• combined (estrogen and progestogen containing) hor-monal contraception associated with inhibition of ovulation:
• oral
• intravaginal
• transdermal
• progestogen-only hormonal contraception associatedwith inhibition of ovulation:
• oral
• injectable
• implantable

You may not qualify if:

• Other Forms of PH or PAH
• Use of PAH medications for more than 6 weeks prior to screening
• Symptoms or signs of clinically relevant lung disease, including TLC \< 70%, FEV1/FVC \<60%, and DLCO \<45%, respectively
• Signs of left heart failure with reduced or preserved ejection fraction, including LVEF \<50%, LAVI \>34 ml/m2, E/é ≥15, or permanent atrial fibrillation, respectively.
• History of severe bleeding/haemorrhage
• Therapy with prostacyclin and/or antithrombotic agents
• eGFR \<30 ml/min/m2.
• Pregnancy or breastfeeding
• Hypersensitivity to the active substance or to any of the excipients

Sponsors & Collaborators

• Philipps University Marburg: lead
• MSD Sharp & Dohme GmbH, Germany: collaborator

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Interventions

ACE-011

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Karen Olsson, Prof. Dr.

  Hannover Medical School Department of Respiratory Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

SIRIUS Study Team

CONTACT

+4915114980915; sirius@kks.uni-marburg.de

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: prospective, non-randomized, multi-center, proof-of-concept

Study Record Dates

• First Submitted: November 19, 2025
• First Posted: December 5, 2025
• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): October 1, 2028
• Last Updated: December 5, 2025

Record last verified: 2025-11