Impact of Sotatercept on Pulmonary Artery and Right Ventricle Remodeling Imaging Assessed With 68Ga-FAPI PET/CT in Patients With PAH

NCT07357974 | Not Yet Recruiting Phase 1

• 1 other identifier: 29BRC24.0296
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Pulmonary Arterial Hypertension (PAH)

Keywords

[68Ga]Ga-FAPI PET/CT (FAPI); [68Ga]Ga-MAA lung perfusion PET/CT

Outcome Measures

Primary Outcomes (1)

• Vascular remodeling as assessed by [68Ga] Ga-FAPI uptake of pulmonary arteries on PET/CT imaging.

  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.

  at baseline

Secondary Outcomes (23)

• 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.

Study Arms (1)

PET/CT

EXPERIMENTAL

Diagnostic Test: [68Ga]Ga-FAPI PET/CT; Diagnostic Test: [68Ga]Ga-MAA PET/CT

Interventions

[68Ga]Ga-FAPI PET/CT DIAGNOSTIC_TEST

\[68Ga\]Ga-FAPI PET/CT

PET/CT

[68Ga]Ga-MAA PET/CT DIAGNOSTIC_TEST

\[68Ga\]Ga-MAA PET/CT

PET/CT

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Brest: lead

Study Sites (1)

Chu Brest

Brest, Finistere, 29200, France

Location

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Cécile Tromeur

  CHU BREST

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Cécile Tromeur

CONTACT

+33230337602; Cecile.tromeur@chu-brest.fr

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This pilot study explores innovative imaging techniques, including \[⁶⁸Ga\]Ga-FAPI PET/CT and \[⁶⁸Ga\]Ga-MAA lung perfusion PET/CT , which have not yet been fully evaluated in patients with pulmonary arterial hypertension. Patients with an indication for sotatercept will be screened for eligibility according to predefined inclusion criteria. Eligible participants will be enrolled in the study. Each participant will undergo a comprehensive assessment including \[⁶⁸Ga\]Ga-FAPI PET/CT and \[⁶⁸Ga\]Ga-MAA PET/CT at baseline and at a follow-up visit 24 weeks later.

Study Record Dates

• First Submitted: December 2, 2025
• First Posted: January 22, 2026
• Study Start: January 1, 2026
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): December 1, 2028
• Last Updated: January 22, 2026

Record last verified: 2026-01

Locations

FR (1)