Impact of Sotatercept on Pulmonary Artery and Right Ventricle Remodeling Imaging Assessed With 68Ga-FAPI PET/CT in Patients With PAH: a Pilot Study
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Vascular remodeling as assessed by [68Ga] Ga-FAPI uptake of pulmonary arteries on PET/CT imaging.
研究概览
简要总结
Pulmonary arterial hypertension (PAH) is a rare, progressive disease characterized by structural changes in the pulmonary arteries, leading to increased pulmonary vascular resistance and elevated pulmonary arterial pressure and, if untreated, right heart failure. Diagnosis requires a comprehensive evaluation, including right heart catheterization performed in specialized centers.
Despite advances in the understanding and management of the disease, PAH remains a severe condition. Current approved therapies primarily target three key pathways involved in endothelial dysfunction: the endothelin, nitric oxide, and prostacyclin pathways. Pulmonary arterial remodeling is characterized by alterations in endothelial cells, smooth muscle cells, and fibroblasts, with fibroblast activation and macrophage involvement contributing to disease progression.
Two positron emission tomography/computed tomography (PET/CT) imaging approaches are currently under investigation in PAH. [⁶⁸Ga]Ga-FAPI PET/CT targets activated fibroblasts and enables noninvasive assessment of fibroblast activity and tissue remodeling. [⁶⁸Ga]Ga-MAA lung perfusion PET/CT is an emerging imaging technique that provides higher spatial resolution and sensitivity than conventional lung perfusion imaging and allows evaluation of regional pulmonary perfusion.
Sotatercept is a novel fusion protein that modulates signaling within the transforming growth factor-beta (TGF-β) superfamily by binding select ligands involved in vascular remodeling. Its mechanism of action is distinct from that of currently approved PAH therapies. Sotatercept has been evaluated in clinical development programs, including the PULSAR and STELLAR studies. Reported adverse events include epistaxis, dizziness, increased hemoglobin levels, and changes in blood pressure.
This study is designed with the following objectives:
Primary objective: To assess pulmonary vascular remodeling in patients with PAH using [⁶⁸Ga]Ga-FAPI PET/CT imaging.
Secondary objectives: To evaluate [⁶⁸Ga]Ga-FAPI uptake and regional lung perfusion using [⁶⁸Ga]Ga-MAA lung perfusion PET/CT imaging at predefined study time points.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years
- •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:
- •Idiopathic PAH
- •Heritable PAH
- •Drug/toxine-induced PAH
- •PAH associated with connective tissue disease
- •PAH associated with simple, congenital systemic-to- pulmonary shunts at least 1year following repair
- •Patients under bi or tri-background-therapy
- •Symptomatic PAH classified WHO FC II or III
- •Patients will be started on Sotatercept
- •Ability to adhere to study visit schedule and understand and comply with all the protocol requirement.
- •Ability to understand and provide written informed consent
排除标准
- •Diagnosis of PH WHO Groups 2, 3, 4, or 5
- •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.
- •Hemoglobin at screening above gender-specific ULN, per local laboratory test
- •Pregnant or breastfeeding women
- •Any of the following clinical laboratory values at the Screening visit:
- •eGFR < 30 mL/min/1.73 m2 (as defined by MDRD equation)
- •Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), or total bilirubin levels > 3 × ULN
- •Platelet count < 50,000/mm3 (< 50.0 × 109/L)
- •Known allergic reaction to sotatercept (ACE-011), its excipients, or luspatercept
研究组 & 干预措施
PET/CT
干预措施: [68Ga]Ga-FAPI PET/CT (Diagnostic Test)
PET/CT
干预措施: [68Ga]Ga-MAA PET/CT (Diagnostic Test)
结局指标
主要结局
Vascular remodeling as assessed by [68Ga] Ga-FAPI uptake of pulmonary arteries on PET/CT imaging.
时间窗: at baseline
A positive uptake will be defined as a ratio of the Standardized uptake value (SUV) max of the pulmonary arteries and the SUVmean of the vascular background activity measured at the center of the left ventricle greater than 1.5.
次要结局
- Change from baseline in [68Ga] Ga-FAPI uptake on pulmonary arteries as assessed by SUVmax at 24 weeks.(At baseline and at 24 weeks.)
- Visual assessment of pulmonary artery [68Ga]Ga-FAPI uptake(At baseline and at 24 weeks.)
- [68Ga] Ga-FAPI uptake on the right ventricule (RV) assessed by SUVmax at 24 weeks.(At week 24)
- RV ventricule dysfunction based on Tricuspid annular plane systolic excursion (TAPSE)<17mm at 24 weeks.(At 24 weeks.)
- Change from baseline in [68Ga] Ga-FAPI uptake on the RV as assessed by SUVmax at 24 weeks.(At baseline and at 24 weeks.)
- Mean pulmonary arterial pressure (mPAP) (in mmHg) at baseline.(At baseline.)
- Cardiac output (CO) (l/mn) at baseline.(At baseline.)
- Right atrial pressure (RAP) (mmHg) at baseline.(at baseline)
- Right ventricular pressure (RVP) (mmHg) at baseline.(At baseline.)
- Pulmonary vascular resistance (PVR) (Wood unit) at baseline.(At baseline.)
- Mean pulmonary arterial pressure (mPAP) (mmHg) at 24 weeks.(At 24 weeks.)
- Cardiac output (CO) (l/mn) at 24 weeks.(At 24 weeks.)
- Right atrial pressure (RAP) (mmHg) at 24 weeks.(At 24 weeks.)
- Right ventricular pressure (RVP) (mmHg) at 24 weeks.(at baseline)
- 6 minutes walking test result (6MWT) (meters) at baseline.(At baseline.)
- Vascular remodeling on [68Ga]Ga-FAPI PET/CT is correlated with Nt-proBNP measure in PAH patients(at baseline)
- 6 minutes walking test result (6MWT) (meters) at 24 weeks.(At 24 weeks.)
- NYHA functional class at baseline.(At baseline.)
- NYHA functional class at 24 weeks.(At 24 weeks.)
- N-terminal pro B natriuretic peptide (NT-pro-BNP) (pg/ml) at baseline(At baseline.)
- N-terminal pro B natriuretic peptide (NT-pro-BNP) (pg/ml) at 24 weeks.(At 24 weeks.)
- Quality of life (QOL) assessed by emPHasis-10 scale at baseline.(At baseline.)
- QOL assessed by emPHasis-10 scale at 24 weeks.(At 24 weeks.)