Clinical trial NCT06855329: PRospective phenotypIng and Multi-omic Endotyping of Progressive Pulmonary Fibrosis
Official title: PRIME-PPF: PRospective phenotypIng and Multi-omic Endotyping of Progressive Pulmonary Fibrosis
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Progressive Pulmonary Fibrosis
Interstitial Lung Disease
Keywords: Progressive pulmonary fibrosis
Interstitial lung disease
PRIME
PRIME-PPF
PPF
Lead sponsor: University of Massachusetts, Worcester
Sponsor class: OTHER
Collaborators: name: University of Michigan
name: University of Virginia
name: Johannes Gutenberg University Mainz
name: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
First posted: 2025-03-03
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with non-idiopathic pulmonary fibrosis (non-IPF) fibrosing ILD, including connective tissue disease associated ILD (CTD-ILD), fibrotic hypersensitivity pneumonitis (fHP) and non-IPF idiopathic interstitial pneumonia (IIP).

Brief summary: This is a prospective, observational cohort study. Participants with non-idiopatic pulmonary fibrosis, interstitial lung disease (ILD) will be followed for 24 months to systematically collect clinical, imaging, and biospecimen data. The primary objective is to optimize progressive pulmonary fibrosis (PPF) classification and establish PPF incidence for key ILD subtypes. Additional exploratory objectives are to 1) Prospectively validate a novel PPF classifier and assess performance durability over time, and 2) Determine whether multi-dimensional PPF prediction outperforms component approaches.

Detailed description: This is a prospective, cohort study with no study investigational therapy prescribed. Patients with non-idiopathic pulmonary fibrosis (non-IPF) fibrosing ILD, including connective tissue disease associated ILD (CTD-ILD), fibrotic hypersensitivity pneumonitis (fHP) and non-IPF idiopathic interstitial pneumonia (IIP) will be recruited. Consented participants with non-IPF ILD will be carefully phenotyped with extensive clinical, physiological, and imaging data. After confirmation of eligibility, participants will undergo protocolized follow-up over 24 months. Clinical data and blood biospecimens will be collected at protocolized time points throughout the study.

The primary outcome is 12-month transplant-free survival (TFS), following a 12-month observation period with TFS defined as the time from 12-month PFT to death, lung transplant or censoring at 12 months or earlier if lost to follow-up. This research will determine whether a ≥10% relative decline in FVC occurring during the 12-month observation period is associated with TFS over the subsequent 12 months. The investigators will then explore other proposed PPF criteria using the same approach. Additionally, the investigators will determine test performance characteristics of a novel proteomic biomarker for predicting PPF at 12 months and compare performance of this classifier to a multi-dimensional approach that incorporates clinical data and quantitative CT data.

Eligibility criteria: Inclusion Criteria:

* Age 18-80 years with a diagnosis of non-IPF fibrosing ILD due to CTD-ILD, fHP, or non-IPF IIP based on central review
* Diagnosis of Fibrotic ILD as determined by site investigator.
* Willingness to comply with study procedures and follow-up.
* Provide written informed consent.

Exclusion Criteria:

* Site diagnosis of fibrosing ILD \>5 years prior to Visit 1 (Screening and Baseline Visit).
* Minimal ILD, defined as reticular opacities and/or ground-glass opacities without architectural distortion (traction bronchiolectasis/bronchiectasis or honeycombing) affecting \< 5% of the lung on centralized evaluation of HRCT at Visit 1 (Screening and Baseline Visit). High quality historical chest HRCT may be used if performed within 90 days prior to Visit 1.
* Extent of emphysema \>15% of total lung volume or greater than extent of fibrosis based on central, qualitative assessment of HRCT at Visit 1. High quality historical chest HRCT may be used if performed within 90 days prior to Visit 1.
* Active malignancy within one year prior to Visit 1 (except for non-melanoma skin cancer requiring local treatment).
* Inability to complete full PFT (spirometry and DLCO) at Visit 1. Historical PFT may be used if performed within 90 days prior to Visit 1.
* Taking nintedanib or nerandomilast at Visit 1.
* Pregnancy at screening or plans to become pregnant during follow-up.
* Participation in an interventional clinical trial for fibrotic ILD at the time of Visit 1, or receipt of an investigational drug within the previous 4 weeks of the enrollment visit (Visit 1) or 5 times the half-life, if longer.

Primary outcomes:
measure: Transplant-free survival (TFS)
timeFrame: 12-months to 24-months (following an observation period from 0 months to 12 months)
Secondary outcomes:
Other outcomes:
Locations:
city: Worcester
country: United States
facility: University of Massachusetts Chan Medical School
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Dallas
country: United States
facility: University of Texas Southwestern
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
Study officials:
affiliation: University of Massachusetts Chan Medical School
name: Fernando J Martinez, MD, MS
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Michigan
name: Justin Oldham, MD, MS
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Michigan
name: Cathie Spino, DSc
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Virginia
name: Imre Noth, MD, MS
role: PRINCIPAL_INVESTIGATOR
affiliation: Johannes Gutenberg University Mainz
name: Michael Kreuter, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Michigan
name: Dinesh Khanna, MD, MS
role: PRINCIPAL_INVESTIGATOR
affiliation: Policlinico Gemelli
name: Luca Richeldi, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: