(S)-2,2',2''-(10-(2-(4-(3-((4-(2-(2-CYANO-4,4-DIFLUOROPYRROLIDIN-1-YL)-2-OXOETHYLCARBAMOYL)-QUINOLIN-6-YL)(METHYL)AMINO)-PROPYL)PIPERAZIN-1-YL)-2-OXOETHYL)-68GA-[1,4,7,10]-TETRAAZACYCLODODECANE-1,4,7-TRIYL)TRIACETATE for Pulmonary arterial hypertension

Inclusion criteria

• {"criterion_text":"- 18 years old or more"}
• {"criterion_text":"- 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 any of the following subtypes: o\tIdiopathic PAH o\tHeritable PAH o\tDrug/toxine-induced PAH o\tPAH associated with connective tissue disease o\tPAH associated with simple, congenital systemic-to- pulmonary shunts at least 1year following repair"}
• {"criterion_text":"- Patients under bi or tri-background-therapy"}
• {"criterion_text":"- Symptomatic PAH classified WHO FC II or III"}
• {"criterion_text":"- Patients will be started on Sotatercept"}
• {"criterion_text":"- Ability to adhere to study visit schedule and understand and comply with all the protocol requirement."}
• {"criterion_text":"- Ability to understand and provide written informed consent"}

Exclusion criteria

• {"criterion_text":"- Diagnosis of PH WHO Groups 2, 3, 4, or 5"}
• {"criterion_text":"- Diagnosis of the following PAH Group 1 subtypes: human immunodeficiency virus (HIV)-associated PAH, PAH associated with portal hypertension, schistosomiasis associated PAH, pulmonary veno occlusive disease and pulmonary capillary hemangiomatosis"}
• {"criterion_text":"- Hemoglobin at screening above gender-specific ULN, per local laboratory test"}
• {"criterion_text":"- Pregnant or breastfeeding women"}
• {"criterion_text":"- Any of the following clinical laboratory values at the Screening Visit: -\teGFR < 30 mL/min/1.73 m2 (as defined by MDRD equation) -\tSerum alanine aminotransferase (ALT), aspartate aminotransferase (AST), or total bilirubin levels > 3 × ULN"}
• {"criterion_text":"- A known allergy has been identified with sotatercept (ACE-011), its excipients, or luspatercept."}

Primary endpoints

• {"endpoint_text":"- [68Ga] Ga-FAPI uptake (Yes/No) of pulmonary arteries on PET/CT imaging in patients with PAH at V0. The uptake will be assessed visually and outcome considered as success by consensus of two nuclear medicine physicians, using the surrounding vascular background as a reference.","definition_or_measurement_approach":"The uptake will be assessed visually and outcome considered as success by consensus of two nuclear medicine physicians, using the surrounding vascular background as a reference."}

Secondary endpoints

• {"endpoint_text":"- [68Ga] Ga-FAPI uptake on pulmonary arteries at V1 and V2(after 24 weeks treatment with Sotatercept). This will be assessed using a visual scale and the Standardized uptake value (SUVmax).","definition_or_measurement_approach":"Assessed using a visual scale and the Standardized Uptake Value (SUVmax) at V1 and V2 (after 24 weeks of Sotatercept)."}
• {"endpoint_text":"- Regional lung perfusion will be assessed by quantifying the Pulmonary vascular obstruction index (PVOI) on [68Ga]Ga-MAA lung perfusion PET/CT at V1 and V2 (after 24 weeks treatment with Sotatercept)","definition_or_measurement_approach":"Quantification of the Pulmonary vascular obstruction index (PVOI) on [68Ga]Ga-MAA lung perfusion PET/CT at V1 and V2."}
• {"endpoint_text":"- [68Ga] Ga-FAPI uptake on the RV (SUVmax) and a RV ventricule dysfunction based on Tricuspid annular plane systolic excursion (TAPSE)<17mm.","definition_or_measurement_approach":"RV uptake measured by SUVmax on FAPI PET/CT and RV dysfunction defined as TAPSE < 17 mm."}
• {"endpoint_text":"- [68Ga] Ga-FAPI uptake on the RV (SUVmax) at V1 and V2","definition_or_measurement_approach":"RV SUVmax measured on FAPI PET/CT at V1 and V2."}
• {"endpoint_text":"- [68Ga] Ga-FAPI uptake on pulmonary arteries (SUVmax) will be correlated with hemodynamic parameters on RHC (PAPm, CO, RAP, RVP, PVR)","definition_or_measurement_approach":"Correlation analyses between pulmonary artery SUVmax and right heart catheterization hemodynamic parameters (mean pulmonary artery pressure (PAPm), cardiac output (CO), right atrial pressure (RAP), right ventricular pressure (RVP), pulmonary vascular resistance (PVR))."}
• {"endpoint_text":"- [68Ga] Ga-FAPI uptake on pulmonary arteries (SUVmax) will be correlated with 6 minutes walking test result (6MWT) in PAH patients","definition_or_measurement_approach":"Correlation between pulmonary artery SUVmax and 6-minute walk test distance (6MWT)."}
• {"endpoint_text":"- [68Ga] Ga-FAPI uptake on pulmonary arteries (SUVmax) will be correlated with NYHA functional class in PAH patients","definition_or_measurement_approach":"Correlation between pulmonary artery SUVmax and NYHA functional class."}
• {"endpoint_text":"- [68Ga] Ga-FAPI uptake on pulmonary arteries (SUVmax) will be correlated with Nt-proBNP measure in PAH patients","definition_or_measurement_approach":"Correlation between pulmonary artery SUVmax and NT-proBNP levels."}
• {"endpoint_text":"- [68Ga] Ga-FAPI uptake on pulmonary arteries (SUVmax) will be correlated with quality of life (Emphasis 10) measure in PAH patients","definition_or_measurement_approach":"Correlation between pulmonary artery SUVmax and quality of life measure (Emphasis 10)."}
• {"endpoint_text":"- Qualitative and quantitative evaluation of imaging parameters, including image quality and reproducibility, acquisition time, radiation dose, ease of interpretation, technical success rate, inter-operator variability, and the impact of acquisition parameters on biomarker quantification.","definition_or_measurement_approach":"Qualitative and quantitative assessments of imaging parameters: image quality, reproducibility, acquisition time, radiation dose, ease of interpretation, technical success rate, inter-operator variability, and assessment of acquisition parameter impact on biomarker quantification."}

France

Earliest CTIS Part Ii Submission Date

12-08-2025

Latest Decision Or Authorization Date

24-10-2025

Processing Time Days

73

Number Of Sites

1

Number Of Participants

15

Primary sponsor

Full Name

Centre Hospitalier Regional Et Universitaire De Brest

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France

Third parties

• {"country":"","full_name":"MSD","duties_or_roles":"Monetary support","organisation_type":""}