Pulmonary Arterial Hypertension PAHPhase 4RECOMPENSENCT06658522
Right Ventricular Compensation With Sotatercept: A Prospective Single Arm Open Label Phase 4 Study to Evaluate the Effects of Sotatercept on Right Ventricular Function in Pulmonary Arterial Hypertension (RECOMPENSE)
A Phase 4 study testing Sotatercept in people with Pulmonary Arterial Hypertension PAH and Pulmonary Arterial Hypertension WHO Group I, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.
Trial summary
Pulmonary arterial hypertension (PAH) is a progressive disease characterized by vascular remodelling resulting in elevated pressures in the pulmonary artery (PA). This elevated pressure ultimately leads to fulminant right heart failure. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Pulmonary Arterial Hypertension PAH, Pulmonary Arterial Hypertension WHO Group I, Pulmonary Arterial Hypertension
- What is being tested?
- Sotatercept
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteNetherlands
- Study dates
- 14 May 2025to 1 May 2026
- Phase
- Phase 4
- 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
- Adult patients between 18-70 years of age
- Able to provide signed informed consent
- WHO FC II to IV
- NTproBNP \> 300 ng/L
- PAH etiology belonging to one of the following groups (Nice classification):
- Idiopathic PAH
Show all 15Show fewer
- Heritable PAH
- Hemodynamic diagnosis of PAH confirmed by RHC during screening showing:
- mPAP \> 20 mmHg
- Pulmonary capillary wedge pressure (PCWP) or left ventricular end diastolic pressure (LVEDP) ≤ 15 mmHg
- PVR ≥ 4WU (320 dyn.sec.cm-5)
- For patients treated with oral diuretics, treatment dose must have been stable at least 1 month prior to RHC during the screening period
- All patients are on stable background therapy at least 3 months prior to RHC during the screening period
- Women of childbearing potential must have a negative pregnancy test at screening and agree to use reliable methods of contraception
- Males must agree to use a condom during sexual contact with a pregnant female or female of childbearing potential while participating in the study. Males should refrain from donating blood or sperm for the duration for the study and for 16 weeks after last dose of sotatercept
Who cannot join
- Any contraindication to treatment with sotatercept
- Body weight \< 40 kg
- Body mass index (BMI) \> 35kg/m2
- Pregnancy, breastfeeding, or intention to become pregnant during the study
- Recently started (\< 8 weeks prior to informed consent signature) or planned cardio-pulmonary rehabilitation program
- Known concomitant life-threatening disease with a life expectancy \< 12 months
Show all 26Show fewer
- Any condition likely to affect protocol or treatment compliance
- Hospitalization for PAH within 3 months prior to informed consent signature
- Left atrial volume per body surface area ≥ 43mL/m2 by echocardiography or CMR
- Valvular disease grade 2 or higher
- History of pulmonary embolism or deep vein thrombosis
- Documented moderate to severe chronic obstructive pulmonary disease
- Documented moderate to severe restrictive lung disease
- Historical evidence of significant coronary artery disease
- Diabetes mellitus
- Active cancer
- Systolic blood pressure \< 90 mmHg
- Need for dialysis
- Responders to acute vasoreactivity testing based on medical history
- Treatment with another investigational drug (planned, or taken within the 3 months prior to study treatment initiation)
- Claustrophobia
- Permanent cardiac pacemaker, automatic internal cardioverter
- Metallic implant (e.g. defibrillator, neurostimulator, hearing aid, infusion device)
- Atrial fibrillation, multiple premature ventricular or atrial contractions , or any other condition that would interfere with proper cardiac gating during CMR.
- History of major bleeding
- Hemoglobin above ULN for age and gender
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Netherlands1 site, 1 recruiting
- Recruiting
Amsterdam UMC, location VUMC
Amsterdam, North Holland, 1081HV
Eszter Nora Toth, M.D., 0204444444 ext. 41526, e.n.toth@amsterdamumc.nl
Harm Jan Bogaard, prof. M.D. PhD
About this study
Official title: RECOMPENSE: Right vEntricular COMPENsation With SotatercEpt: a Prospective Single Arm Open Label Phase 4 Study to Evaluate the Effects of Sotatercept on Right Ventricular Function in Pulmonary Arterial Hypertension
Pulmonary arterial hypertension (PAH) is a progressive disease characterized by vascular remodelling resulting in elevated pressures in the pulmonary artery (PA). This elevated pressure ultimately leads to fulminant right heart failure. Current therapeutic options are limited and are centred around vasodilatory medications such as phosphodiesterase-5 inhibitors and prostacyclin. While these medications allow for the widening of blood vessels that are narrowed due to remodelling, they have no effect on the remodelling itself.
Sotatercept is a novel medication which targets the BMPR2/TGF-β pathway and restore a pro- and anti- proliferative balance to ultimately counteract vascular remodelling. Recent phase 2 and 3 trials showed that treatment with sotatercept led to lower resistance and pressure in the pulmonary vasculature and improved exercise tolerance. However, these results were not coupled with an increase in cardiac output, a change that is seen with other PAH-medications with a primarily vasodilatory effect. These results suggest that cardiac work is reduced and cardiac efficiency is improved in patients being treated with sotatercept, in contrast with conventional PAH therapies. This is a potentially beneficial effect that may result in improved disease control in the long-term. Our study aims to explore the effect of sotatercept on cardiac work and function. We hypothesize that the effects of sotatercept are more beneficial for cardiac function than that of traditional PAH medications.
Read more
All participants included in the trial will undergo a screening visit in which it will be checked that all inclusion criteria and no exclusion criteria are met. The screening visit involves a physical exam, blood draw, 6-minute walk test, right heart catheterization (RHC) and cardiac magnetic resonance imaging (cMRI) with contrast to assess fibrosis.
Upon inclusion, all participants will receive a subcutaneous injection of sotatercept starting at a dose of 0.3 mg/kg. Participants will return to the hospital every three weeks for a blood draw, physical examination and an adverse event review. If the laboratory values (specifically haemoglobin and platelet counts) stay stable after the first dose, the dosage will be escalated to 0.7 mg/kg. The dose will not be escalated beyond 0.7 mg/kg.
After 24 weeks of receiving sotatercept, there will be an end of treatment visit including a physical exam, 6-minute walk test, right heart catheterization (RHC) and cardiac magnetic resonance imaging (cMRI) with contrast material.
Read the detailed description
Recent phase 2 and phase 3 studies showed that treatment of PAH patients with the Activin ligand trap sotatercept results in significant reductions in PVR in addition to improvements in exercise capacity, as measured by 6MWD, and other clinical outcomes while effects on cardiac output were only minimal.
Assessment of intrinsic RV function is essential to understanding the effects of sotatercept on the myocardium. In order to make this assessment in a load-independent fashion, pressure-volume loops must be used. RV-PA coupling, the relationship between RV end systolic elastance and pulmonary arterial elastance, describes the relationship between RV contractility and RV afterload. The preservation of RV function rests on the delicate balance of RV coupling. In order to preserve RV function in PAH, an increase in afterload will be met with increased RV contractility. Uncoupling occurs in PAH when RV contractility fails to increase to match an elevated afterload leading to maladaptation and RV failure. Decreases in mPAP typically lead to decreases in RV contractility while exercise or sympathetic stimulation will lead to increased contractility.
This is a prospective, single center, single-arm, open-label, phase 4 study to evaluate the effects of sotatercept on RV function and dimensions in PAH. Twenty PAH patients will be enrolled at the Amsterdam UMC and receive open label subcutaneous sotatercept (starting dose, 0.3 mg per kilogram of body weight; target dose, 0.7 mg per kilogram) for 24 weeks. After signing informed consent and completion of screening, and before receiving the first drug dose, patients undergo right heart catheterization (RHC), and cMRI to determine pump function graphs and cardiac volumes and RV fibrosis. These procedures are repeated after the end of the treatment (EOT). The treatment period starts with the first dose of IMP and ends on the last day of IMP which is the day of the last dose of IMP at premature discontinuation or at week 24 ± 7 days. There is an additional follow-up period of 5 weeks after study completion.
Patients enrolled in the study will receive subcutaneous sotatercept (starting dose, 0.3 mg per kilogram of body weight; target dose, 0.7 mg per kilogram) for 24 weeks. After giving informed consent and before receiving the first drug dose, patients undergo RHC and cMRI to determine pump function graphs and cardiac volumes and assess fibrosis. Additionally, patients will undergo a physician assessment and blood sampling. All of these procedures will be repeated at the end of the treatment (EOT) visit after 24 weeks.
Recent phase 2 and phase 3 studies showed that treatment of pulmonary arterial hypertension (PAH) patients with the activin ligand trap sotatercept results in significant reductions in pulmonary vascular resistance (PVR) in addition to improvements in exercise capacity, as measured by the six minute walk distance (6MWD), and other clinical outcomes while effects on cardiac output (CO) are only minimal. These results contrast sharply with the results of studies with other PAH specific drugs, in which improvements in 6MWD were always reflected by profound increases in cardiac output. The fact that resting cardiac output after sotatercept treatment is not increased, may partly be attributed to a concomitant increase in blood hemoglobin levels, allowing a lower cardiac output to preserve oxygen delivery to the tissues. Moreover, conventional PAH drugs are not entirely pulmonary specific and cause systemic vasodilation, requiring an increase in cardiac output to maintain systemic blood pressure. In contrast, a slight increase in systemic blood pressure was observed in PAH patients treated with sotatercept. Considering these fundamental differences resulting from treatment with sotatercept, we hypothesize that the effects of sotatercept on cardiac function are much more beneficial than the effects of conventional PAH specific drugs.
This is a prospective, single center, single-arm, open-label, phase 4 study to evaluate the effects of sotatercept on RV function and dimensions in PAH. Twenty PAH patients will be enrolled at the Amsterdam UMC and receive open label subcutaneous sotatercept (starting dose, 0.3 mg per kilogram of body weight; target dose, 0.7 mg per kilogram) for 24 weeks
Patients enrolled in the study will receive subcutaneous sotatercept (starting dose, 0.3 mg per kilogram of body weight; target dose, 0.7 mg per kilogram) for 24 weeks. After giving informed consent and before receiving the first drug dose, patients undergo RHC and cMRI to determine pump function graphs and cardiac volumes and assess fibrosis. Additionally, patients will undergo a physician assessment and blood sampling. All of these procedures will be repeated at the end of the treatment (EOT) visit after 24 weeks.
- Conditions
- Pulmonary Arterial Hypertension PAH, Pulmonary Arterial Hypertension WHO Group I, Pulmonary Arterial Hypertension
- Being tested
- Sotatercept
- Keywords
- Pulmonary arterial hypertension, PAH, Right Ventricle, Sotatercept
- 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.
SotaterceptDrug
Participants will receive open label subcutaneous sotatercept (starting dose, 0.3 mg per kilogram of body weight; target dose, 0.7 mg per kilogram) for 24 weeks
| Study group | Role | What they receive |
|---|---|---|
| Sotatercept treatment | Experimental | PAH patients receiving subcutaneous sotatercept injection Receives: Drug: Sotatercept |
What is being measured
The primary outcome is the main question the study is designed to answer.
Power per beat
mean pulmonary arery pressure (mPAP) x stroke volume (SV)
Measured: From enrollment to end of study at 24 weeks
Right ventricular pulmonary artery coupling
End systolic elastance (Ees)/ Arterial elastance (Ea) as derived from pressure-volume loops using right heart catheterization
Measured: From enrollment to end of study at 24 weeks
Secondary outcomes (13)
Right ventricular end systolic volume
Right ventricular end systolic volume as measured by cardiac magnetic resonance imaging
Measured: From enrollment to the end of study at 24 weeks
Right ventricular end diastolic volume
Right ventricular end diastolic volume as measured by cardiac magnetic resonance imaging
Measured: From enrollment to the end of study at 24 weeks
Right ventricular ejection fraction
Right ventricular ejection fraction as measured by cardiac magnetic resonance imaging
Measured: From enrollment to the end of study at 24 weeks
Right ventricular mass
Right ventricular mass as measured by cardiac magnetic resonance imaging
Measured: From enrollment to the end of study at 24 weeks
Stroke volume
Stroke volume as measured by cardiac magnetic resonance imaging derived aortic flow
Measured: From enrollment to the end of study at 24 weeks
Left ventricular end diastolic volume
Left ventricular end diastolic volume as measured by cardiac magnetic resonance imaging
Measured: From enrollment to the end of study at 24 weeks
Left ventricular end systolic volume
Left ventricular end systolic volume as measured by cardiac magnetic resonance imaging
Measured: From enrollment to the end of study at 24 weeks
Left ventricular ejection fraction
Left ventricular ejection fraction as measured by cardiac magnetic resonance imaging
Measured: From enrollment to the end of study at 24 weeks
Left ventricular mass
Left ventricular mass as measured by cardiac magnetic resonance imaging
Measured: From enrollment to the end of study at 24 weeks
End-systolic elastance (Ees)
End systolic elastance measured using pressure-volume loops derived from right heart catheteriazation
Measured: From enrollment to the end of study at 24 weeks
Arterial elastance (Ea)
Arterial elastance measured using pressure-volume loops derived from right heart catheteriazation
Measured: From enrollment to the end of study at 24 weeks
End-diastolic elastance (Eed)
End-diastolic elastance measured using pressure-volume loops derived from right heart catheteriazation
Measured: From enrollment to the end of study at 24 weeks
Right ventricular fibrosis
Righ ventricular fibrosis derived from extracellular volume measurements using Modified Look-Locker inversion recovery MRI sequence
Measured: From enrollment to the end of study at 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Oct 2024
- Study start14 May 2025
- Primary completion1 May 2026 (estimated)
- Study completion1 May 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for Pulmonary Arterial Hypertension PAHStudies of the same condition, open and under way.
- More trials run by Amsterdam UMC, location VUmcThe sponsor's other registered studies.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Amsterdam UMC, location VUmc
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Principal investigator, Harm Jan Bogaard, VU University of Amsterdam
- Investigators
- Harm Jan Bogaard, M.D., PhD, Principal investigator, Amsterdam UMC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06658522
- Sponsor's protocol ID
- 2024-512543-23-00
- Other IDs
- 2024-512543-23-00
- Acronym
- RECOMPENSE
- Status last verified
- Sep 2025
- First submitted
- 24 Oct 2024
- Last updated
- 22 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: A decision regarding data sharing will be made upon opening the study due to privacy concerns
Publications
Vonk Noordegraaf A, Westerhof BE, Westerhof N. The Relationship Between the Right Ventricle and its Load in Pulmonary Hypertension. J Am Coll Cardiol. 2017 Jan 17;69(2):236-243. doi: 10.1016/j.jacc.2016.10.047.
PubMed 28081831Sniderman AD, Fitchett DH. Vasodilators and pulmonary arterial hypertension: the paradox of therapeutic success and clinical failure. Int J Cardiol. 1988 Aug;20(2):173-81. doi: 10.1016/0167-5273(88)90261-6. No abstract available.
PubMed 3061937Joshi SR, Liu J, Bloom T, Karaca Atabay E, Kuo TH, Lee M, Belcheva E, Spaits M, Grenha R, Maguire MC, Frost JL, Wang K, Briscoe SD, Alexander MJ, Herrin BR, Castonguay R, Pearsall RS, Andre P, Yu PB, Kumar R, Li G. Sotatercept analog suppresses inflammation to reverse experimental pulmonary arterial hypertension. Sci Rep. 2022 May 12;12(1):7803. doi: 10.1038/s41598-022-11435-x.
PubMed 35551212Gomberg-Maitland M, McLaughlin VV, Badesch DB, Ghofrani HA, Hoeper MM, Humbert M, Preston IR, Souza R, Waxman AB, de Oliveira Pena J, Lu JT, Manimaran S, Gibbs JSR. Long-Term Effects of Sotatercept on Right Ventricular Function: Results From the PULSAR Study. JACC Heart Fail. 2023 Oct;11(10):1457-1459. doi: 10.1016/j.jchf.2023.05.030. Epub 2023 Jul 12. No abstract available.
PubMed 37452806Souza R, Badesch DB, Ghofrani HA, Gibbs JSR, Gomberg-Maitland M, McLaughlin VV, Preston IR, Waxman AB, Grunig E, Kopec G, Meyer G, Olsson KM, Rosenkranz S, Lin J, Johnson-Levonas AO, de Oliveira Pena J, Humbert M, Hoeper MM. Effects of sotatercept on haemodynamics and right heart function: analysis of the STELLAR trial. Eur Respir J. 2023 Sep 21;62(3):2301107. doi: 10.1183/13993003.01107-2023. Print 2023 Sep.
PubMed 37696565Hoeper MM, Badesch DB, Ghofrani HA, Gibbs JSR, Gomberg-Maitland M, McLaughlin VV, Preston IR, Souza R, Waxman AB, Grunig E, Kopec G, Meyer G, Olsson KM, Rosenkranz S, Xu Y, Miller B, Fowler M, Butler J, Koglin J, de Oliveira Pena J, Humbert M; STELLAR Trial Investigators. Phase 3 Trial of Sotatercept for Treatment of Pulmonary Arterial Hypertension. N Engl J Med. 2023 Apr 20;388(16):1478-1490. doi: 10.1056/NEJMoa2213558. Epub 2023 Mar 6.
PubMed 36877098Humbert M, McLaughlin V, Gibbs JSR, Gomberg-Maitland M, Hoeper MM, Preston IR, Souza R, Waxman AB, Ghofrani HA, Escribano Subias P, Feldman J, Meyer G, Montani D, Olsson KM, Manimaran S, de Oliveira Pena J, Badesch DB. Sotatercept for the treatment of pulmonary arterial hypertension: PULSAR open-label extension. Eur Respir J. 2023 Jan 6;61(1):2201347. doi: 10.1183/13993003.01347-2022. Print 2023 Jan.
PubMed 36041750Humbert M, McLaughlin V, Gibbs JSR, Gomberg-Maitland M, Hoeper MM, Preston IR, Souza R, Waxman A, Escribano Subias P, Feldman J, Meyer G, Montani D, Olsson KM, Manimaran S, Barnes J, Linde PG, de Oliveira Pena J, Badesch DB; PULSAR Trial Investigators. Sotatercept for the Treatment of Pulmonary Arterial Hypertension. N Engl J Med. 2021 Apr 1;384(13):1204-1215. doi: 10.1056/NEJMoa2024277.
PubMed 33789009Handoko ML, de Man FS, Allaart CP, Paulus WJ, Westerhof N, Vonk-Noordegraaf A. Perspectives on novel therapeutic strategies for right heart failure in pulmonary arterial hypertension: lessons from the left heart. Eur Respir Rev. 2010 Mar;19(115):72-82. doi: 10.1183/09059180.00007109.
PubMed 20956170Messroghli DR, Radjenovic A, Kozerke S, Higgins DM, Sivananthan MU, Ridgway JP. Modified Look-Locker inversion recovery (MOLLI) for high-resolution T1 mapping of the heart. Magn Reson Med. 2004 Jul;52(1):141-6. doi: 10.1002/mrm.20110.
PubMed 15236377Waxman AB, Systrom DM, Manimaran S, de Oliveira Pena J, Lu J, Rischard FP. SPECTRA Phase 2b Study: Impact of Sotatercept on Exercise Tolerance and Right Ventricular Function in Pulmonary Arterial Hypertension. Circ Heart Fail. 2024 May;17(5):e011227. doi: 10.1161/CIRCHEARTFAILURE.123.011227. Epub 2024 Apr 4.
PubMed 38572639
Study at a glance
From the registry record, last updated by the sponsor on 22 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- RECOMPENSE: Right vEntricular COMPENsation With SotatercEpt: a Prospective Single Arm Open Label Phase 4 Study to Evaluate the Effects of Sotatercept on Right Ventricular Function in Pulmonary Arterial Hypertension
- ClinicalTrials.gov ID
- NCT06658522
- Acronym / sponsor ID
- RECOMPENSE / 2024-512543-23-00
- Conditions
- Pulmonary Arterial Hypertension PAH, Pulmonary Arterial Hypertension WHO Group I, Pulmonary Arterial Hypertension
- Keywords
- Pulmonary arterial hypertension, PAH, Right Ventricle, Sotatercept
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Amsterdam UMC, location VUmcUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 14 May 2025 (actual)
- Primary completion
- 1 May 2026 (estimated)
- Study completion
- 1 May 2026 (estimated)
- First posted
- 26 Oct 2024 (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.
Pulmonary arterial hypertension (PAH) is a progressive disease characterized by vascular remodelling resulting in elevated pressures in the pulmonary artery (PA). This elevated pressure ultimately leads to fulminant right heart failure. Current therapeutic options are limited and are centred around vasodilatory medications such as phosphodiesterase-5 inhibitors and prostacyclin. While these medications allow for the widening of blood vessels that are narrowed due to remodelling, they have no effect on the remodelling itself.
Sotatercept is a novel medication which targets the BMPR2/TGF-β pathway and restore a pro- and anti- proliferative balance to ultimately counteract vascular remodelling. Recent phase 2 and 3 trials showed that treatment with sotatercept led to lower resistance and pressure in the pulmonary vasculature and improved exercise tolerance. However, these results were not coupled with an increase in cardiac output, a change that is seen with other PAH-medications with a primarily vasodilatory effect. These results suggest that cardiac work is reduced and cardiac efficiency is improved in patients being treated with sotatercept, in contrast with conventional PAH therapies. This is a potentially beneficial effect that may result in improved disease control in the long-term. Our study aims to explore the effect of sotatercept on cardiac work and function. We hypothesize that the effects of sotatercept are more beneficial for cardiac function than that of traditional PAH medications.
All participants included in the trial will undergo a screening visit in which it will be checked that all inclusion criteria and no exclusion criteria are met. The screening visit involves a physical exam, blood draw, 6-minute walk test, right heart catheterization (RHC) and cardiac magnetic resonance imaging (cMRI) with contrast to assess fibrosis.
Upon inclusion, all participants will receive a subcutaneous injection of sotatercept starting at a dose of 0.3 mg/kg. Participants will return to the hospital every three weeks for a blood draw, physical examination and an adverse event review. If the laboratory values (specifically haemoglobin and platelet counts) stay stable after the first dose, the dosage will be escalated to 0.7 mg/kg. The dose will not be escalated beyond 0.7 mg/kg.
After 24 weeks of receiving sotatercept, there will be an end of treatment visit including a physical exam, 6-minute walk test, right heart catheterization (RHC) and cardiac magnetic resonance imaging (cMRI) with contrast material.
Detailed description
Recent phase 2 and phase 3 studies showed that treatment of PAH patients with the Activin ligand trap sotatercept results in significant reductions in PVR in addition to improvements in exercise capacity, as measured by 6MWD, and other clinical outcomes while effects on cardiac output were only minimal.
Assessment of intrinsic RV function is essential to understanding the effects of sotatercept on the myocardium. In order to make this assessment in a load-independent fashion, pressure-volume loops must be used. RV-PA coupling, the relationship between RV end systolic elastance and pulmonary arterial elastance, describes the relationship between RV contractility and RV afterload. The preservation of RV function rests on the delicate balance of RV coupling. In order to preserve RV function in PAH, an increase in afterload will be met with increased RV contractility. Uncoupling occurs in PAH when RV contractility fails to increase to match an elevated afterload leading to maladaptation and RV failure. Decreases in mPAP typically lead to decreases in RV contractility while exercise or sympathetic stimulation will lead to increased contractility.
This is a prospective, single center, single-arm, open-label, phase 4 study to evaluate the effects of sotatercept on RV function and dimensions in PAH. Twenty PAH patients will be enrolled at the Amsterdam UMC and receive open label subcutaneous sotatercept (starting dose, 0.3 mg per kilogram of body weight; target dose, 0.7 mg per kilogram) for 24 weeks. After signing informed consent and completion of screening, and before receiving the first drug dose, patients undergo right heart catheterization (RHC), and cMRI to determine pump function graphs and cardiac volumes and RV fibrosis. These procedures are repeated after the end of the treatment (EOT). The treatment period starts with the first dose of IMP and ends on the last day of IMP which is the day of the last dose of IMP at premature discontinuation or at week 24 ± 7 days. There is an additional follow-up period of 5 weeks after study completion.
Patients enrolled in the study will receive subcutaneous sotatercept (starting dose, 0.3 mg per kilogram of body weight; target dose, 0.7 mg per kilogram) for 24 weeks. After giving informed consent and before receiving the first drug dose, patients undergo RHC and cMRI to determine pump function graphs and cardiac volumes and assess fibrosis. Additionally, patients will undergo a physician assessment and blood sampling. All of these procedures will be repeated at the end of the treatment (EOT) visit after 24 weeks.
Recent phase 2 and phase 3 studies showed that treatment of pulmonary arterial hypertension (PAH) patients with the activin ligand trap sotatercept results in significant reductions in pulmonary vascular resistance (PVR) in addition to improvements in exercise capacity, as measured by the six minute walk distance (6MWD), and other clinical outcomes while effects on cardiac output (CO) are only minimal. These results contrast sharply with the results of studies with other PAH specific drugs, in which improvements in 6MWD were always reflected by profound increases in cardiac output. The fact that resting cardiac output after sotatercept treatment is not increased, may partly be attributed to a concomitant increase in blood hemoglobin levels, allowing a lower cardiac output to preserve oxygen delivery to the tissues. Moreover, conventional PAH drugs are not entirely pulmonary specific and cause systemic vasodilation, requiring an increase in cardiac output to maintain systemic blood pressure. In contrast, a slight increase in systemic blood pressure was observed in PAH patients treated with sotatercept. Considering these fundamental differences resulting from treatment with sotatercept, we hypothesize that the effects of sotatercept on cardiac function are much more beneficial than the effects of conventional PAH specific drugs.
This is a prospective, single center, single-arm, open-label, phase 4 study to evaluate the effects of sotatercept on RV function and dimensions in PAH. Twenty PAH patients will be enrolled at the Amsterdam UMC and receive open label subcutaneous sotatercept (starting dose, 0.3 mg per kilogram of body weight; target dose, 0.7 mg per kilogram) for 24 weeks
Patients enrolled in the study will receive subcutaneous sotatercept (starting dose, 0.3 mg per kilogram of body weight; target dose, 0.7 mg per kilogram) for 24 weeks. After giving informed consent and before receiving the first drug dose, patients undergo RHC and cMRI to determine pump function graphs and cardiac volumes and assess fibrosis. Additionally, patients will undergo a physician assessment and blood sampling. All of these procedures will be repeated at the end of the treatment (EOT) visit after 24 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Sotatercept treatment | Experimental | Drug: SotaterceptPAH patients receiving subcutaneous sotatercept injection |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Adult patients between 18-70 years of age
- Able to provide signed informed consent
- WHO FC II to IV
- NTproBNP \> 300 ng/L
- PAH etiology belonging to one of the following groups (Nice classification):
Key exclusion criteria (26 listed)
- Any contraindication to treatment with sotatercept
- Body weight \< 40 kg
- Body mass index (BMI) \> 35kg/m2
- Pregnancy, breastfeeding, or intention to become pregnant during the study
- Recently started (\< 8 weeks prior to informed consent signature) or planned cardio-pulmonary rehabilitation program
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 |
|---|---|---|
| SotaterceptParticipants will receive open label subcutaneous sotatercept (starting dose, 0.3 mg per kilogram of body weight; target dose, 0.7 mg per kilogram) for 24 weeks | Drug | Sotatercept treatment |
Primary outcome
Power per beat
Time frame: From enrollment to end of study at 24 weeks
mean pulmonary arery pressure (mPAP) x stroke volume (SV)
Right ventricular pulmonary artery coupling
Time frame: From enrollment to end of study at 24 weeks
End systolic elastance (Ees)/ Arterial elastance (Ea) as derived from pressure-volume loops using right heart catheterization
13 secondary outcomes
Right ventricular end systolic volume
Time frame: From enrollment to the end of study at 24 weeks
Right ventricular end diastolic volume
Time frame: From enrollment to the end of study at 24 weeks
Right ventricular ejection fraction
Time frame: From enrollment to the end of study at 24 weeks
Right ventricular mass
Time frame: From enrollment to the end of study at 24 weeks
Stroke volume
Time frame: From enrollment to the end of study at 24 weeks
Left ventricular end diastolic volume
Time frame: From enrollment to the end of study at 24 weeks
Left ventricular end systolic volume
Time frame: From enrollment to the end of study at 24 weeks
Left ventricular ejection fraction
Time frame: From enrollment to the end of study at 24 weeks
Left ventricular mass
Time frame: From enrollment to the end of study at 24 weeks
End-systolic elastance (Ees)
Time frame: From enrollment to the end of study at 24 weeks
Arterial elastance (Ea)
Time frame: From enrollment to the end of study at 24 weeks
End-diastolic elastance (Eed)
Time frame: From enrollment to the end of study at 24 weeks
Right ventricular fibrosis
Time frame: From enrollment to the end of study at 24 weeks
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 22 Sep 2025.
- Background: PubMed 28081831Vonk Noordegraaf A, Westerhof BE, Westerhof N. The Relationship Between the Right Ventricle and its Load in Pulmonary Hypertension. J Am Coll Cardiol. 2017 Jan 17;69(2):236-243. doi: 10.1016/j.jacc.2016.10.047.
- Background: PubMed 3061937Sniderman AD, Fitchett DH. Vasodilators and pulmonary arterial hypertension: the paradox of therapeutic success and clinical failure. Int J Cardiol. 1988 Aug;20(2):173-81. doi: 10.1016/0167-5273(88)90261-6. No abstract available.
- Background: PubMed 35551212Joshi SR, Liu J, Bloom T, Karaca Atabay E, Kuo TH, Lee M, Belcheva E, Spaits M, Grenha R, Maguire MC, Frost JL, Wang K, Briscoe SD, Alexander MJ, Herrin BR, Castonguay R, Pearsall RS, Andre P, Yu PB, Kumar R, Li G. Sotatercept analog suppresses inflammation to reverse experimental pulmonary arterial hypertension. Sci Rep. 2022 May 12;12(1):7803. doi: 10.1038/s41598-022-11435-x.
- Background: PubMed 37452806Gomberg-Maitland M, McLaughlin VV, Badesch DB, Ghofrani HA, Hoeper MM, Humbert M, Preston IR, Souza R, Waxman AB, de Oliveira Pena J, Lu JT, Manimaran S, Gibbs JSR. Long-Term Effects of Sotatercept on Right Ventricular Function: Results From the PULSAR Study. JACC Heart Fail. 2023 Oct;11(10):1457-1459. doi: 10.1016/j.jchf.2023.05.030. Epub 2023 Jul 12. No abstract available.
- Background: PubMed 37696565Souza R, Badesch DB, Ghofrani HA, Gibbs JSR, Gomberg-Maitland M, McLaughlin VV, Preston IR, Waxman AB, Grunig E, Kopec G, Meyer G, Olsson KM, Rosenkranz S, Lin J, Johnson-Levonas AO, de Oliveira Pena J, Humbert M, Hoeper MM. Effects of sotatercept on haemodynamics and right heart function: analysis of the STELLAR trial. Eur Respir J. 2023 Sep 21;62(3):2301107. doi: 10.1183/13993003.01107-2023. Print 2023 Sep.
- Background: PubMed 36877098Hoeper MM, Badesch DB, Ghofrani HA, Gibbs JSR, Gomberg-Maitland M, McLaughlin VV, Preston IR, Souza R, Waxman AB, Grunig E, Kopec G, Meyer G, Olsson KM, Rosenkranz S, Xu Y, Miller B, Fowler M, Butler J, Koglin J, de Oliveira Pena J, Humbert M; STELLAR Trial Investigators. Phase 3 Trial of Sotatercept for Treatment of Pulmonary Arterial Hypertension. N Engl J Med. 2023 Apr 20;388(16):1478-1490. doi: 10.1056/NEJMoa2213558. Epub 2023 Mar 6.
- Background: PubMed 36041750Humbert M, McLaughlin V, Gibbs JSR, Gomberg-Maitland M, Hoeper MM, Preston IR, Souza R, Waxman AB, Ghofrani HA, Escribano Subias P, Feldman J, Meyer G, Montani D, Olsson KM, Manimaran S, de Oliveira Pena J, Badesch DB. Sotatercept for the treatment of pulmonary arterial hypertension: PULSAR open-label extension. Eur Respir J. 2023 Jan 6;61(1):2201347. doi: 10.1183/13993003.01347-2022. Print 2023 Jan.
- Background: PubMed 33789009Humbert M, McLaughlin V, Gibbs JSR, Gomberg-Maitland M, Hoeper MM, Preston IR, Souza R, Waxman A, Escribano Subias P, Feldman J, Meyer G, Montani D, Olsson KM, Manimaran S, Barnes J, Linde PG, de Oliveira Pena J, Badesch DB; PULSAR Trial Investigators. Sotatercept for the Treatment of Pulmonary Arterial Hypertension. N Engl J Med. 2021 Apr 1;384(13):1204-1215. doi: 10.1056/NEJMoa2024277.
- Background: PubMed 20956170Handoko ML, de Man FS, Allaart CP, Paulus WJ, Westerhof N, Vonk-Noordegraaf A. Perspectives on novel therapeutic strategies for right heart failure in pulmonary arterial hypertension: lessons from the left heart. Eur Respir Rev. 2010 Mar;19(115):72-82. doi: 10.1183/09059180.00007109.
- Background: PubMed 15236377Messroghli DR, Radjenovic A, Kozerke S, Higgins DM, Sivananthan MU, Ridgway JP. Modified Look-Locker inversion recovery (MOLLI) for high-resolution T1 mapping of the heart. Magn Reson Med. 2004 Jul;52(1):141-6. doi: 10.1002/mrm.20110.
- Background: PubMed 38572639Waxman AB, Systrom DM, Manimaran S, de Oliveira Pena J, Lu J, Rischard FP. SPECTRA Phase 2b Study: Impact of Sotatercept on Exercise Tolerance and Right Ventricular Function in Pulmonary Arterial Hypertension. Circ Heart Fail. 2024 May;17(5):e011227. doi: 10.1161/CIRCHEARTFAILURE.123.011227. Epub 2024 Apr 4.
- Individual participant dataSharing planned: Undecided. A decision regarding data sharing will be made upon opening the study due to privacy concerns
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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.
Harm Jan Bogaard, M.D., PhD principal investigator
Amsterdam UMC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Sotatercept in people with Pulmonary Arterial Hypertension PAH and Pulmonary Arterial Hypertension WHO Group I, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.
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 15 inclusion and 26 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: looking for participants now, as of the sponsor's last update on 22 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 Harm Jan Bogaard, M.D., PhD (+31 0 20 444 4444 ext. 4782, hj.bogaard@amsterdamumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Power per beat (time frame: From enrollment to end of study at 24 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06658522, which also lists 11 linked publications.
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 22 Sep 2025; AzTrials last refreshed its copy on 5 Nov 2026.