A Study to Test Whether Nerandomilast Can Help Slow Down Changes in the Lung in People With a Family History of Pulmonary Fibrosis

• Nerandomilast (Drug), also known as BI 1015550, JASCAYD®: Nerandomilast
• Placebo (Drug): Placebo

Primary outcomes

• Time to physiologic or radiologic worsening of ILA/ILD over the whole trial [up to 164 weeks]: Defined as relative decline in forced vital capacity (FVC) % predicted of >10% from baseline; or absolute decline in diffusing capacity of the lungs for carbon monoxide (DLCO) % predicted >10% from baseline; or absolute increase in weighted reticulovascular score (wRVS) >2% and total disease extent (TDE) >2.5% on chest high resolution CT scan (HRCT), as measured by e-Lung Quantitative HRCT scoring, from baseline

Secondary outcomes

• Absolute change from baseline in wRVS on e-Lung Quantitative HRCT scoring at weeks 26, 52, and 104 [at baseline, at weeks 26, 52 and 104]
• Absolute change from baseline in TDE on e-Lung Quantitative HRCT scoring at weeks 26, 52, and 104 [at baseline, at weeks 26, 52 and 104]
• Absolute change from baseline in FVC (% predicted) at weeks 26, 52, and 104 [at baseline, at weeks 26, 52 and 104]
• Absolute change from baseline in DLCO (% predicted) at weeks 26, 52, and 104 [at baseline, at weeks 26, 52 and 104]
• Time to relative decline from baseline in FVC (% predicted) of >10% over 52 weeks and over the whole trial [up to 164 weeks]
• Time to absolute decline from baseline in FVC (% predicted) of >5% over 52 weeks and over the whole trial [up to 164 weeks]
• Time to absolute decline from baseline in DLCO (% predicted) of >10% over 52 weeks and over the whole trial [up to 164 weeks]
• Time to absolute increase in wRVS >2% and TDE >2.5% on chest HRCT, as measured by e-lung quantitative HRCT scoring over 52 weeks and over the whole trial [up to 164 weeks]
• Time to physiologic or radiologic worsening of ILA/ILD over 52 weeks [up to 52 weeks]

Sex: All, ages: 40 Years to any

Inclusion Criteria:

* Individuals ≥40 years of age at the time of first signed informed consent at Visit 1a
* Participants must have at least 1 first-degree relative (biological parent, sibling, or child) with confirmed pulmonary fibrosis (idiopathic pulmonary fibrosis \[IPF\], idiopathic nonspecific interstitial pneumonia \[NSIP\], and/or pulmonary fibrosis due to known genetic cause \[e.g. short telomere syndrome, mucin 5B (MUC5B) mutation, surfactant protein mutations\])
* High resolution computed tomography (HRCT) scan with evidence of interstitial lung abnormalities involving at least 5% of a single lung zone or interstitial lung disease (ILD), based on central evaluation
* Forced vital capacity (FVC) ≥80% of predicted normal at Visit 1b
* Diffusing capacity of the lungs for carbon monoxide (DLCO) corrected for hemoglobin ≥70% of predicted normal at Visit 1b Further inclusion criteria apply.

Exclusion Criteria:

* Prior known pulmonary fibrosis that, in the opinion of the Investigator, requires treatment with approved therapies
* Prebronchodilator forced expiratory volume in 1 second (FEV1)/FVC <0.7 at Visit 1b
* HRCT findings consistent with probable or definite usual interstitial pneumonia (UIP) pattern
* Any medical condition that is known to predispose to the development of pulmonary fibrosis (e.g. known connective tissue disease)
* Prior or current use of nerandomilast, nintedanib, or pirfenidone Further exclusion criteria apply.

NIH grants: 2025