A double blind, randomized, placebo-controlled trial evaluating the efficacy and safety of BI 1015550 over at least 52 weeks in patients with Progressive Fibrosing Interstitial Lung Diseases (PF-ILDs)

Progressive fibrosing interstitial lung diseases (PF-ILDs) and idiopathic
pulmonary fibrosis (IPF) share common pathophysiological features; alveolar
epithelial cell damage and consequences, subsequent dysregulated repair of
extracellular matrix and loss of normal parenchymal architecture and lung. In
IPF, fibroblasts exhibit unregulated proliferation and differentiate into
myofibroblasts. The latter is considered to be the hallmark cell in the
development and establishment of pulmonary fibrosis. Several growth factors are
involved in the proliferation, migration and transdifferentiation of the
fibroblast and myofibroblast pool in pulmonary fibrosis.

Currently, nintedanib and pirfenidone are the only drugs authorized for the
treatment of IPF and are recommended in the recent clinical practice guideline
ATS/ERS/JRS/ALT for the treatment of idiopathic pulmonary fibrosis. Nintedanib
is also approved in the US, European Union and many other countries for the
treatment of other fibrosing ILDs with progressive phenotype. Despite the
availability of these drugs, medical care remains high with these devastating
diseases.

This study has been transitioned to CTIS with ID 2024-512803-37-00 check the CTIS register for the current data.

The aim of this study is to evaluate the efficacy, safety and tolerability of
BI 1015550 9 mg BID and 18 mg BID compared to placebo in patients with PF-ILD,
in addition to the patient's standard of care. The primary objective of this
study is to demonstrate the ability of BI 1015550 to reduce lung function
decline based on forced vital capacity (FVC) between baseline and week 52
compared to placebo.

Patients who will participate in the study will be screened for eligibility
after signing the consent form. After signing the consent form, the first visit
(Visit 1) will be conducted to determine the patient's eligibility. Eligible
patients attend the randomization visit (Visit 2) to collect all clinical and
safety information and to review all inclusion and exclusion criteria.

Patients are randomized in a 1:1:1 ratio to CI 1015550 9 mg BID, CI 1015550 18
mg BID or placebo and then enter the treatment phase for at least 52 weeks.

The randomization of patients will be stratified based on the presence of
background antifibrotic therapy (AF group vs. non-AF group).
- Non-AF group: patients not being treated with an approved antifibrotic
medication (nintedanib or pirfenidone) in the last 8 weeks at study entry
(e.g., previously treated with antifibrotics but discontinued that treatment or
patients never previously treated with antifibrotics treated with
antifibrotics).
- AF group: Patients on stable treatment with an approved antifibrotic drug
(e.g. nintedanib or pirfenidone) for at least 12 weeks at study entry and are
expected to continue on this background treatment after randomization.

The research will be conducted in 2 parts. Treatment Period A of the study will
consist of visits 2 through 10, up to one year after randomization. Treatment
Period B begins upon completion of the visit at week 52 (visit 10); patients
will continue treatment with blinded trial drug in treatment period B and have
trial visits every 12 weeks. Assuming a respective recruitment period
(approximately 11 months), the first randomized patients can receive trial
treatment for up to 130 weeks.

Around the time the last randomized patient reaches 52 weeks of treatment, all
patients still on blinded study treatment will have an end of treatment visit
and an end of study visit (if applicable). The study ends when all patients
have completed these visits.

See protocol section 3.1

This trial will include an option for participants and participant caregivers
to complete anonymized questionnaires to provide feedback on their clinical
trial experience. Providing this feedback is not required for trial
participation, and information collected from these questionnaires will not be
analyzed as part of the clinical data for the trial (see Section 10.6)

One group will receive a 9 mg tablet of BI 1015550 twice daily, a second group
will receive an 18 mg tablet of BI 1015550 twice daily, and the third group
will receive a placebo tablet twice daily.

Patients with PF-ILD treated with BI 1015550 have the potential benefit of
slowing decline in lung function, improving symptoms, and improving long-term
quality of life.

The toxicology data support the administration of BI 1015550 to women and men
in planned phase III clinical studies in patients with IPF and other forms of
progressive pulmonary fibrosis, regardless of background antifibrotic therapy,
except for pregnant or breast-feeding women.

Data from the phase II study 1305-0013 in patients with IPF indicated a
beneficial treatment effect of 18 mg BI 1015550 twice daily, with forced vital
capacity (FVC) maintenance for 12 weeks, along with an acceptable safety and
tolerability profile to support of further investigation in Phase III clinical
trials as a treatment for PF-ILD and other forms of progressive pulmonary
fibrosis.