Early recognition of progressive lung fibrosis in systemic rheumatic diseases: a characterization of the pulmonary environment through extracellular vesicles, advanced and functional imaging

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08], Diseases [C] - Skin and Connective Tissue Diseases [C17]

Trial duration

30 May 2025 → ongoing

Decision date (initial)

2024-11-11

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Ministero della Salute (Project code: PNRR-MCNT2-2023-12377894)

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Diagnosis

To compare baseline FAPI PET/CT measures in CTD-ILD patients who will and will not experience lung functional progression at 12-month follow-up.

Secondary objectives 2

1. To correlate FAPI PET/CT measures with AI-read HRCT outputs and circulating EV proteomic and transcriptomic characteristics
2. Exploratory objective: To correlate FAPI PET/CT measures with BALF EV proteomic and transcriptomic characteristics

Conditions and MedDRA coding

Patients with connective tissue diseases at high risk of interstial lung disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Female and male aged between 18 and 75 years
2. Signature of informed consent
3. A clinical diagnosis of SSc, RA, SS, IIM, or UCTD that must adhere to internationally accepted classification criteria
4. A high risk of ILD based on autoantibody profile, specifically: anti-Scl70+ or anti-RNAPIII+ for SSc, anti-CCP+ and/or RF+ for RA, anti-RoSSA+ and anti-LaSSB+ for primary SS, anti-synthetase+ for IIM. For UCTD patients, the enrollment criteria will be adapted to match those of Interstitial Pneumonia with Autoimmune Features (IPAF), with patients exhibiting one clinical feature of CTD and one serological domain criterion (e.g., ANA positive with nucleolar pattern, RF and anti-CCP positivity, anti-RoSSA and anti-LaSSB positivity, anti-Scl70 positivity) while not meeting the classification criteria for any other CTD
5. Evidence of ILD based on an HRCT documenting the presence of interstitial changes involving at least 10% of the parenchyma within the previous 6 weeks
6. Either naive to immunosuppressants or having been on a stable immunosuppressive regimen for the 3 months preceding FAPI PET/CT. Treatment with rituximab must be not administered in the previous 24 weeks
7. Specifically, patients that are candidates to BALF collection must have functional or radiological evidence of ILD deterioration to justify microbiological and cytological characterization of the lung environment before treatment upgrade

Exclusion criteria 9

1. Current treatment with corticosteroids > 10 mg of prednisone
2. Women of childbearing potential tested positive at the urine pregnancy test performed just before FAPI PET/CT procedure
3. Pregnancy, breastfeeding, or intention to undergo pregnancy within 6 months from the PET/CT scan
4. Men who have a partner of childbearing age who intends or is likely to become pregnant in the 6 months following PET/CT
5. Claustrophobia and/or inability to tolerate PET acquisition that would have an impact on the collection of a good quality scan
6. Poor peripheral arterial and/or venous access that would interfere with radiopharmaceutical administration and/or blood sampling
7. Specifically, the patient’s candidate for BALF collection must not have contraindications to the procedure, namely severe refractory hypoxemia and/or O2 therapy, uncontrolled active bronchospasm, history of unstable angina, history of myocardial infarction, history of unstable arrhythmias, platelet count <20,000/mm3 in the preceding 4 weeks, international normalized ratio or activated partial thromboplastin time ratio >1.5 evaluated in the preceding 4 weeks
8. Clinical evidence of infection or positive microbiological tests on BALF analysis if performed
9. known allergy or hypersensitivity to any component of the FAPI tracer

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The following measures will be evaluated in FAPI PET-CT: pattern and distribution of FAPI uptake, mean and maximum Standardized Uptake Value (SUV mean and SUV max) of pulmonary fibrotic lesions, fibrotic active volume (FAV), total fibrosis (calculated as the product of SUV mean and the fibrotic active volume), uptake ratio between fibrotic and healthy lung tissue. These measures will be compared between CTD-ILD patients with and without progressive phenotypes at the 12-month follow-up

Secondary endpoints 2

1. AI-collected measures of lung anatomy (including lung texture, airway, and vascular measures) and serum EV single-protein quantity and RNA expression measures
2. Exploratory endpoint: BALF EV single-protein quantity and RNA expression measures

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Sponsor organisation

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Address

Largo Francesco Vito 1

City

Rome

Postcode

00168

Country

Italy

Scientific contact point

Organisation

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Contact name

Silvia Laura Bosello

Public contact point

Organisation

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Contact name

Silvia Laura Bosello

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 17 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications