Pulmonary Arterial Hypertension (PAH)Phase 2SIRIUSNCT07266519
SIRIUS - Initial Combination Therapy With an Endothelin Receptor Antagonist, a Phosphodiesterase-5 Inhibitor and Sotatercept in Patients With Newly Diagnosed Pulmonary Arterial Hypertension
A Phase 2 study testing Sotatercept 0.3 mg/kg escalating to 0.7 mg/kg and Sotatercept in people with Pulmonary Arterial Hypertension (PAH), run by Philipps University Marburg.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Pulmonary Arterial Hypertension (PAH)
- What is being tested?
- Sotatercept 0.3 mg/kg escalating to 0.7 mg/kg and Sotatercept
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- No sites listed yet
- Study dates
- 1 Jul 2026to Oct 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
- intrauterine device (IUD)
- intrauterine hormone-releasing system (IUS)
- bilateral tubal occlusion
- vasectomized partner
- sexual abstinence
- Male participants with female partner(s) of childbearing potential are eligible to participate in the study if they agree to the following during treatment and until 304 daysmonths after the last administration of study medication:
- Inform any and all partner(s) of their participation in a clinical drug study and the need to comply with contraception instructions as directed by the investigator.
- Male participants are required to use a condom during treatment and until 30 days4 months after the last administration of study medication.
- Female partners of male participants who have not undergone a vasectomy with the absence of sperm confirmed or a bilateral orchiectomy should consider use of effective methods of contraception during treatment and until 30 days4 months after the last administration of study medication.
- Sperm donation is not allowed during treatment and until 4 months after the last administration of study medication.
Who cannot join
- 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
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- eGFR <30 ml/min/m2.
- Pregnancy or breastfeeding
- Hypersensitivity to the active substance or to any of the excipients
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: SIRIUS - A Prospective, Non-randomized, Open-label, Proof-of-concept Study of Initial Combination Therapy With an Endothelin Receptor Antagonist, a Phosphodiesterase-5 Inhibitor and Sotatercept in Patients With Newly Diagnosed Pulmonary Arterial Hypertension A Single-arm, Multi-center, Interventional Phase II Study
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)
- Being tested
- Sotatercept 0.3 mg/kg escalating to 0.7 mg/kg, Sotatercept
- Keywords
- triple therapy, PAH, treatment-naiive
- Medical subject headings
- Pulmonary Arterial Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sotatercept 0.3 mg/kg escalating to 0.7 mg/kgDrug
subcutaneously administration in 3-weekly intervals
SotaterceptDrug
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
| Study group | Role | What they receive |
|---|---|---|
| Single arm | Experimental | Treatment arm Receives: Drug: Sotatercept 0.3 mg/kg escalating to 0.7 mg/kg; Drug: Sotatercept |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Dec 2025
- Study start1 Jul 2026 (estimated)
- Primary completionOct 2028 (estimated)
- Study completionOct 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pulmonary Arterial Hypertension (PAH)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- prospective, non-randomized, multi-center, proof-of-concept
- Masking
- None (open label)
- Enrolment
- 25 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Philipps University Marburg
- Sponsor type
- University, hospital or other
- Collaborators
- MSD Sharp & Dohme GmbH, Germany
- Responsible party
- Sponsor
- Investigators
- Karen Olsson, Prof. Dr., Principal investigator, Hannover Medical School Department of Respiratory Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07266519
- Sponsor's protocol ID
- KKS-322
- Other IDs
- 2025-522266-67-00, 2025
- Acronym
- SIRIUS
- Status last verified
- Nov 2025
- First submitted
- 19 Nov 2025
- Last updated
- 5 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- SIRIUS - A Prospective, Non-randomized, Open-label, Proof-of-concept Study of Initial Combination Therapy With an Endothelin Receptor Antagonist, a Phosphodiesterase-5 Inhibitor and Sotatercept in Patients With Newly Diagnosed Pulmonary Arterial Hypertension A Single-arm, Multi-center, Interventional Phase II Study
- ClinicalTrials.gov ID
- NCT07266519
- Acronym / sponsor ID
- SIRIUS / KKS-322
- Conditions
- Pulmonary Arterial Hypertension (PAH)
- Keywords
- triple therapy, PAH, treatment-naiive
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 25 participants (estimated)
- Lead sponsor
- Philipps University MarburgUniversity, hospital or other
- Collaborators
- MSD Sharp & Dohme GmbH, Germany
- Study start
- 1 Jul 2026 (estimated)
- Primary completion
- Oct 2028 (estimated)
- Study completion
- Oct 2028 (estimated)
- First posted
- 5 Dec 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- prospective, non-randomized, multi-center, proof-of-concept
| Arm | Type | Receives |
|---|---|---|
| Single arm | Experimental | Drug: Sotatercept 0.3 mg/kg escalating to 0.7 mg/kg, Drug: SotaterceptTreatment arm |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sotatercept 0.3 mg/kg escalating to 0.7 mg/kgsubcutaneously administration in 3-weekly intervals | Drug | Single arm |
| SotaterceptPatients 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 | Drug | Single arm |
Primary outcome
Assessment of the effect on pulmonary vascular resistance (PVR)
Time frame: 24 weeks
Change in PVR from screening at week 24 after 6-months of treatment with triple combination therapy in PAH patients
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Dec 2025.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Karen Olsson, Prof. Dr. principal investigator
Hannover Medical School Department of Respiratory Medicine
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sotatercept 0.3 mg/kg escalating to 0.7 mg/kg and Sotatercept in people with Pulmonary Arterial Hypertension (PAH), run by Philipps University Marburg.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 25 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 5 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact SIRIUS Study Team (+4915114980915, sirius@kks.uni-marburg.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assessment of the effect on pulmonary vascular resistance (PVR) (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Dec 2025; AzTrials last refreshed its copy on 2 Nov 2026.