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)

NCT06658522 | Recruiting Phase 4

• 1 other identifier: 2024-512543-23-00
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Pulmonary Arterial Hypertension PAH; Pulmonary Arterial Hypertension WHO Group I; Pulmonary Arterial Hypertension

Keywords

Pulmonary arterial hypertension; PAH; Right Ventricle; Sotatercept

Outcome Measures

Primary Outcomes (2)

• Power per beat

  mean pulmonary arery pressure (mPAP) x stroke volume (SV)

  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

  From enrollment to end of study at 24 weeks

Secondary Outcomes (13)

• Right ventricular end systolic volume

  From enrollment to the end of study at 24 weeks

• Right ventricular end diastolic volume

  From enrollment to the end of study at 24 weeks

• Right ventricular ejection fraction

  From enrollment to the end of study at 24 weeks

• Right ventricular mass

  From enrollment to the end of study at 24 weeks

• Stroke volume

  From enrollment to the end of study at 24 weeks

Study Arms (1)

Sotatercept treatment

EXPERIMENTAL

PAH patients receiving subcutaneous sotatercept injection

Drug: Sotatercept

Interventions

Sotatercept DRUG

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

Sotatercept treatment

Eligibility Criteria

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

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Amsterdam UMC, location VUmc: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Amsterdam UMC, location VUMC

Amsterdam, North Holland, 1081HV, Netherlands

RECRUITING

Related Publications (11)

• 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.

  PMID: 28081831 BACKGROUND

• Sniderman 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.

  PMID: 3061937 BACKGROUND

• Joshi 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.

  PMID: 35551212 BACKGROUND

• Gomberg-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.

  PMID: 37452806 BACKGROUND

• Souza 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.

  PMID: 37696565 BACKGROUND

• Hoeper 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.

  PMID: 36877098 BACKGROUND

• Humbert 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.

  PMID: 36041750 BACKGROUND

• Humbert 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.

  PMID: 33789009 BACKGROUND

• Handoko 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.

  PMID: 20956170 BACKGROUND

• Messroghli 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.

  PMID: 15236377 BACKGROUND

• Waxman 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.

  PMID: 38572639 BACKGROUND

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Interventions

ACE-011

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Harm Jan Bogaard, M.D., PhD

  Amsterdam UMC

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Harm Jan Bogaard, M.D., PhD

CONTACT

+31 0 20 444 4444; hj.bogaard@amsterdamumc.nl

Eszter N Toth, M.D.

CONTACT

+31 (0) 20 444 4444; e.n.toth@amsterdamumc.nl

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Experimental Pulmonary Medicine

Study Record Dates

• First Submitted: October 24, 2024
• First Posted: October 26, 2024
• Study Start: May 14, 2025
• Primary Completion: May 1, 2026
• Study Completion: May 1, 2026
• Last Updated: September 22, 2025

Record last verified: 2025-09

Locations

NL (1)