PROOF OF CONCEPT STUDY ON THE EFFICACY OF INHALATORY TARGETED IMATINIB NANOFORMULATIONS IN PULMONARY HYPERTENSION AND POST-INFLAMMATORY FIBROSIS. (PROMPTLY)

The PROMPTLY study is a proof-of-concept research project evaluating the efficacy of XHALIP, an innovative inhalable formulation of Imatinib, in treating pulmonary arterial hypertension (PAH) and post-inflammatory fibrosing lung diseases (LFD).

Main Objective To demonstrate the ability of XHALIP to improve the prognosis of PAH and LFD by reducing pulmonary fibrosis and vascular remodeling.

Key Research Questions Is XHALIP effectively absorbed by pathological lung cells? Does it have a beneficial biological effect on cell proliferation and extracellular matrix deposition? Study Plan Preclinical phase: In vitro tests on cells obtained from patients with PAH and LFD.

Absorption and distribution analysis: In vitro lung tissue models to assess drug penetration and effectiveness.

Biological activity assessment: Evaluating XHALIP's ability to inhibit epithelial-mesenchymal transition and cell proliferation.

Participants Patients aged ≥ 18 years diagnosed with PAH or LFD, either candidates for or recipients of lung transplantation.

Biological samples (bronchoalveolar lavage and explanted lung tissues). Methodology Confocal microscopy and flow cytometry to analyze absorption. RT-PCR and Western Blot to assess biological efficacy. Alveolo-capillary models to test drug release and distribution. The study aims to translate preclinical findings into a potential future clinical trial for the development of XHALIP as a novel inhalation-based therapeutic strategy for rare lung diseases.

Study Overview

• Status: Recruiting
• Conditions: Pulmonary Arterial Hypertension (PAH); Lung Fibrosis Interstitial

• Study Type: Observational
• Enrollment (Estimated): 16

Contacts and Locations

• Study Contact: Name: Stefano Ghio, MD; Phone Number: +39 0382503460; Email: s.ghio@smatteo.pv.it

Study Locations

• Italy
  • Pavia, Italy, 27100
    • Recruiting
    • Fondazione IRCCS Policlinico San Matteo
    • Contact: Stefano Ghio, MD; Phone Number: +39 0382503460; Email: s.ghio@smatteo.pv.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The subjects are enrolled at the Fondazione IRCCS Policlinico San Matteo hospital in Pavia, at the SC of Pulmonology of the Foundation.

Description

Inclusion Criteria:

• Patients aged ≥ 18 years diagnosed with fibrosing lung disease, obliterative bronchiolitis, or PAH, who are candidates for or have undergone lung transplantation.
• Obtaining informed consent for all patients enrolled prospectively and all those enrolled retrospectively at their first clinical occurrence at our center.

Exclusion Criteria:

• Suspected or confirmed diagnosis of pulmonary neoplastic disease.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete synthesis and characterization of XHALIP for in vitro studies.	Preparation and stabilization of the dry powder formulation of XHALIP.	two years from the enrollment
Complete synthesis and characterization of XHALIP for in vitro studies.	Evaluation of XHALIP uptake by various cell types obtained ex vivo from patients with LFD and PAH, as well as transplant recipients (endothelial, epithelial, MC, PASMC, inflammatory effector cells), cultured in vitro and in co-culture systems.	two years from the enrollment
Complete synthesis and characterization of XHALIP for in vitro studies.	Evaluation of CD44 expression by various cell types obtained ex vivo from patients with LFD and PAH, as well as transplant recipients (endothelial, epithelial, MC, PASMC, inflammatory effector cells), cultured in vitro and in co-culture systems.	two years from the enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploration of XHALIP Distribution	The distribution of XHALIP will be studied in thin lung tissue cultures (Precision Cut Lung Slices Cells, PCLSC) obtained from lung explants of patients with LFD and PAH.	two years from the enrollment
Exploration of XHALIP Distribution	XHALIP distribution will be explored in a model that replicates the alveolo-capillary microenvironment to analyze its interaction with specific pathological human cells and mucosal/surfactant layers, as well as its ability to cross the alveolo-capillary interface.	two years from the enrollment

Collaborators and Investigators

• Sponsor: Fondazione IRCCS Policlinico San Matteo di Pavia

Study record dates

Study Major Dates

• Study Start (Actual): December 4, 2023
• Primary Completion (Estimated): December 4, 2025
• Study Completion (Estimated): June 4, 2026

Study Registration Dates

• First Submitted: March 21, 2025
• First Submitted That Met QC Criteria: March 31, 2025
• First Posted (Estimated): April 8, 2025

Study Record Updates

• Last Update Posted (Estimated): April 8, 2025
• Last Update Submitted That Met QC Criteria: March 31, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Pulmonary arterial hypertension; PAH; imatinib; LFD; lung fibrosis desease; XHALIP
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Interstitial; Pulmonary Arterial Hypertension; Hypertension; Pulmonary Fibrosis; Fibrosis; Hypertension, Pulmonary
• Other Study ID Numbers: PROMPTLY

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No