Trial Outcomes & Findings for A Study to Find Out Whether BI 1015550 Improves Lung Function in People With Progressive Fibrosing Interstitial Lung Diseases (PF-ILDs) (NCT NCT05321082)

Last Updated: 2026-01-09

Results Overview

The absolute change from baseline in forced vital capacity (FVC) in milliliters \[mL\] at Week 52 is reported. The absolute change from baseline in FVC was analyzed by a restricted maximum likelihood (REML)-based mixed model with repeated measurements (MMRM) comparing the change from baseline in FVC at Week 52 between treatment groups. The analysis included the fixed, categorical effects of treatment, baseline intake of antifibrotic (AF) treatment, and baseline High-resolution Computed Tomography (HRCT) pattern at each visit, as well as the fixed continuous effects of baseline FVC value at each visit. Visits were treated as a repeated measure with an unstructured covariance structure used to model within-patient measurements.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1178 participants

Primary outcome timeframe

The MMRM model is a longitudinal analysis, and it incorporated FVC measurements change from baseline at Week 1, Week 2, Week 6, Week 12, Week 18, Week 26, Week 36, Week 44 and Week 52. Data presented is the FVC adjusted change from baseline at Week 52.

Results posted on

2026-01-09

Participant Flow

This was a multi-centre, multi-national, prospective, randomised, placebo-controlled, double-blind clinical trial, including a treatment period of at least 52 weeks, and a 1-week follow-up period in patients with progressive pulmonary fibrosis. The trial comprised two parts: Treatment Period A lasted up to 52 weeks post-randomisation, followed by Treatment Period B in which patients continued randomised blinded treatment for a variable duration.

All participants were screened for eligibility prior to participation in the trial. Participants attended a specialist site which ensured that they (the participants) strictly met all inclusion and none of the exclusion criteria. Participants were not to be allocated to a treatment sequence if any of the entry criteria were violated.

Participant milestones

Participant milestones
Measure	Placebo Patients with progressive fibrosing interstitial lung disease (PF-ILD) or progressive pulmonary fibrosis (PPF), other than idiopathic pulmonary fibrosis (IPF), were administered placebo matching nerandomilast, taken orally as film-coated tablets twice daily, in the morning and in the evening for an initial 52 weeks, followed by a variable duration till end of trial.	Nerandomilast 9 mg Patients with progressive fibrosing interstitial lung disease (PF-ILD) or progressive pulmonary fibrosis (PPF), other than idiopathic pulmonary fibrosis (IPF), were administered 9 milligrams (mg) nerandomilast, taken orally as film-coated tablets twice daily (18 mg total), in the morning and in the evening for an initial 52 weeks, followed by a variable duration till end of trial.	Nerandomilast 18 mg Patients with progressive fibrosing interstitial lung disease (PF-ILD) or progressive pulmonary fibrosis (PPF), other than idiopathic pulmonary fibrosis (IPF), were administered 18 mg nerandomilast, taken orally as film-coated tablets twice daily (36 mg total), in the morning and in the evening for an initial 52 weeks, followed by a variable duration till end of trial.
Overall Study STARTED	393	393	392
Overall Study Treated	392	393	391
Overall Study Completed treatment up to 52 weeks	317	318	311
Overall Study COMPLETED	271	283	272
Overall Study NOT COMPLETED	122	110	120

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Patients with progressive fibrosing interstitial lung disease (PF-ILD) or progressive pulmonary fibrosis (PPF), other than idiopathic pulmonary fibrosis (IPF), were administered placebo matching nerandomilast, taken orally as film-coated tablets twice daily, in the morning and in the evening for an initial 52 weeks, followed by a variable duration till end of trial.	Nerandomilast 9 mg Patients with progressive fibrosing interstitial lung disease (PF-ILD) or progressive pulmonary fibrosis (PPF), other than idiopathic pulmonary fibrosis (IPF), were administered 9 milligrams (mg) nerandomilast, taken orally as film-coated tablets twice daily (18 mg total), in the morning and in the evening for an initial 52 weeks, followed by a variable duration till end of trial.	Nerandomilast 18 mg Patients with progressive fibrosing interstitial lung disease (PF-ILD) or progressive pulmonary fibrosis (PPF), other than idiopathic pulmonary fibrosis (IPF), were administered 18 mg nerandomilast, taken orally as film-coated tablets twice daily (36 mg total), in the morning and in the evening for an initial 52 weeks, followed by a variable duration till end of trial.
Overall Study Other than listed	40	26	27
Overall Study Lost to Follow-up	0	1	0
Overall Study Withdrawal by Subject	30	34	42
Overall Study Protocol Violation	0	0	1
Overall Study Adverse Event	49	49	48
Overall Study Lack of Efficacy	2	0	1
Overall Study Not treated	1	0	1

Baseline Characteristics

A Study to Find Out Whether BI 1015550 Improves Lung Function in People With Progressive Fibrosing Interstitial Lung Diseases (PF-ILDs)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=392 Participants Patients with progressive fibrosing interstitial lung disease (PF-ILD) or progressive pulmonary fibrosis (PPF), other than idiopathic pulmonary fibrosis (IPF), were administered placebo matching nerandomilast, taken orally as film-coated tablets twice daily, in the morning and in the evening for an initial 52 weeks, followed by a variable duration till end of trial.	Nerandomilast 9 mg n=393 Participants Patients with progressive fibrosing interstitial lung disease (PF-ILD) or progressive pulmonary fibrosis (PPF), other than idiopathic pulmonary fibrosis (IPF), were administered 9 milligrams (mg) nerandomilast, taken orally as film-coated tablets twice daily (18 mg total), in the morning and in the evening for an initial 52 weeks, followed by a variable duration till end of trial.	Nerandomilast 18 mg n=391 Participants Patients with progressive fibrosing interstitial lung disease (PF-ILD) or progressive pulmonary fibrosis (PPF), other than idiopathic pulmonary fibrosis (IPF), were administered 18 mg nerandomilast, taken orally as film-coated tablets twice daily (36 mg total), in the morning and in the evening for an initial 52 weeks, followed by a variable duration till end of trial.	Total n=1176 Participants Total of all reporting groups
Age, Continuous	66.6 Years STANDARD_DEVIATION 10.3 • n=8 Participants	66.5 Years STANDARD_DEVIATION 9.8 • n=7 Participants	66.0 Years STANDARD_DEVIATION 9.8 • n=15 Participants	66.4 Years STANDARD_DEVIATION 10.0 • n=42 Participants
Sex: Female, Male Female	161 Participants n=8 Participants	190 Participants n=7 Participants	171 Participants n=15 Participants	522 Participants n=42 Participants
Sex: Female, Male Male	231 Participants n=8 Participants	203 Participants n=7 Participants	220 Participants n=15 Participants	654 Participants n=42 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	53 Participants n=8 Participants	60 Participants n=7 Participants	57 Participants n=15 Participants	170 Participants n=42 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	339 Participants n=8 Participants	333 Participants n=7 Participants	334 Participants n=15 Participants	1006 Participants n=42 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=8 Participants	0 Participants n=7 Participants	0 Participants n=15 Participants	0 Participants n=42 Participants
Race (NIH/OMB) American Indian or Alaska Native	5 Participants n=8 Participants	6 Participants n=7 Participants	2 Participants n=15 Participants	13 Participants n=42 Participants
Race (NIH/OMB) Asian	149 Participants n=8 Participants	155 Participants n=7 Participants	143 Participants n=15 Participants	447 Participants n=42 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=8 Participants	0 Participants n=7 Participants	0 Participants n=15 Participants	0 Participants n=42 Participants
Race (NIH/OMB) Black or African American	7 Participants n=8 Participants	3 Participants n=7 Participants	6 Participants n=15 Participants	16 Participants n=42 Participants
Race (NIH/OMB) White	226 Participants n=8 Participants	224 Participants n=7 Participants	235 Participants n=15 Participants	685 Participants n=42 Participants
Race (NIH/OMB) More than one race	5 Participants n=8 Participants	5 Participants n=7 Participants	5 Participants n=15 Participants	15 Participants n=42 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=8 Participants	0 Participants n=7 Participants	0 Participants n=15 Participants	0 Participants n=42 Participants
Forced vital capacity (FVC) at baseline	2353.6 Milliliters (mL) STANDARD_DEVIATION 766.2 • n=8 Participants	2325.5 Milliliters (mL) STANDARD_DEVIATION 767.6 • n=7 Participants	2381.4 Milliliters (mL) STANDARD_DEVIATION 722.8 • n=15 Participants	2353.4 Milliliters (mL) STANDARD_DEVIATION 752.3 • n=42 Participants

PRIMARY outcome

Timeframe: The MMRM model is a longitudinal analysis, and it incorporated FVC measurements change from baseline at Week 1, Week 2, Week 6, Week 12, Week 18, Week 26, Week 36, Week 44 and Week 52. Data presented is the FVC adjusted change from baseline at Week 52.

Population: Full Analysis Set (FAS): This patient set included all randomized patients who received at least one dose of study drug. The FAS was used for baseline demographics and characteristics, protocol deviations, and all efficacy analyses, in which patients were analyzed as their randomized treatment group. Only patients with baseline measurement and at least one post-baseline measurement were included.

Outcome measures

Outcome measures
Measure	Placebo n=391 Participants Patients with progressive fibrosing interstitial lung disease (PF-ILD) or progressive pulmonary fibrosis (PPF), other than idiopathic pulmonary fibrosis (IPF), were administered placebo matching nerandomilast, taken orally as film-coated tablets twice daily, in the morning and in the evening for an initial 52 weeks, followed by a variable duration till end of trial.	Nerandomilast 9 mg n=390 Participants Patients with progressive fibrosing interstitial lung disease (PF-ILD) or progressive pulmonary fibrosis (PPF), other than idiopathic pulmonary fibrosis (IPF), were administered 9 milligrams (mg) nerandomilast, taken orally as film-coated tablets twice daily (18 mg total), in the morning and in the evening for an initial 52 weeks, followed by a variable duration till end of trial.	Nerandomilast 18 mg n=390 Participants Patients with progressive fibrosing interstitial lung disease (PF-ILD) or progressive pulmonary fibrosis (PPF), other than idiopathic pulmonary fibrosis (IPF), were administered 18 mg nerandomilast, taken orally as film-coated tablets twice daily (36 mg total), in the morning and in the evening for an initial 52 weeks, followed by a variable duration till end of trial.
Absolute Change From Baseline in Forced Vital Capacity (FVC) in Milliliters [mL] at Week 52	-165.77 Milliliters (mL) Interval -190.52 to -141.03	-84.64 Milliliters (mL) Interval -109.63 to -59.65	-98.59 Milliliters (mL) Interval -123.74 to -73.44

SECONDARY outcome

Timeframe: From first administration of trial drug (Nerandomilast or Placebo) till end of study, up to 26.2 months.

Population: Full Analysis Set (FAS): This patient set included all randomised patients who received at least one dose of study drug. The FAS was used for baseline demographics and characteristics, protocol deviations, and all efficacy analyses, in which patients were analysed as their randomised treatment group.

Time to first occurrence of any of the components of the composite endpoint - acute interstitial lung disease (ILD) exacerbation, first hospitalisation for respiratory cause, or death (whichever occurred first) - is reported as the number of participants who experienced any of these events during the trial. Acute exacerbation of ILD describes an acute, clinically significant, respiratory deterioration characterized by evidence of new widespread alveolar abnormality with all of the following: Acute worsening or development of dyspnea typically with less than 1 month duration, computed tomography with new bilateral ground-glass opacity and/or consolidation superimposed on a background pattern consistent with fibrosing ILD, and deterioration not fully explained by cardiac failure or fluid overload. If more than one component occurred on the same day, the patient was counted under the first event according to the following hierarchy: acute ILD exacerbation, hospitalization, death.

Outcome measures

Outcome measures
Measure	Placebo n=392 Participants Patients with progressive fibrosing interstitial lung disease (PF-ILD) or progressive pulmonary fibrosis (PPF), other than idiopathic pulmonary fibrosis (IPF), were administered placebo matching nerandomilast, taken orally as film-coated tablets twice daily, in the morning and in the evening for an initial 52 weeks, followed by a variable duration till end of trial.	Nerandomilast 9 mg n=393 Participants Patients with progressive fibrosing interstitial lung disease (PF-ILD) or progressive pulmonary fibrosis (PPF), other than idiopathic pulmonary fibrosis (IPF), were administered 9 milligrams (mg) nerandomilast, taken orally as film-coated tablets twice daily (18 mg total), in the morning and in the evening for an initial 52 weeks, followed by a variable duration till end of trial.	Nerandomilast 18 mg n=391 Participants Patients with progressive fibrosing interstitial lung disease (PF-ILD) or progressive pulmonary fibrosis (PPF), other than idiopathic pulmonary fibrosis (IPF), were administered 18 mg nerandomilast, taken orally as film-coated tablets twice daily (36 mg total), in the morning and in the evening for an initial 52 weeks, followed by a variable duration till end of trial.
Key Secondary Endpoint: Time to First Occurrence of Any of the Components of the Composite Endpoint: Time to First Acute ILD Exacerbation, First Hospitalisation for Respiratory Cause, or Death (Whichever Occurred First) Over the Duration of the Trial Acute ILD exacerbation as first event	44 Participants	34 Participants	30 Participants
Key Secondary Endpoint: Time to First Occurrence of Any of the Components of the Composite Endpoint: Time to First Acute ILD Exacerbation, First Hospitalisation for Respiratory Cause, or Death (Whichever Occurred First) Over the Duration of the Trial Hospitalisation for respiratory cause as first event	82 Participants	70 Participants	74 Participants
Key Secondary Endpoint: Time to First Occurrence of Any of the Components of the Composite Endpoint: Time to First Acute ILD Exacerbation, First Hospitalisation for Respiratory Cause, or Death (Whichever Occurred First) Over the Duration of the Trial Death as first event	17 Participants	12 Participants	9 Participants

SECONDARY outcome

Timeframe: From first administration of trial drug (Nerandomilast or Placebo) till end of study, up to 26.2 months.

Time to first acute ILD exacerbation or death over the duration of the trial is reported as the number of patients who experienced either event. Acute exacerbation of ILD describes an acute, clinically significant, respiratory deterioration characterized by evidence of new widespread alveolar abnormality with all of the following: Acute worsening or development of dyspnea typically with less than 1 month duration, computed tomography with new bilateral ground-glass opacity and/or consolidation superimposed on a background pattern consistent with fibrosing ILD, and deterioration not fully explained by cardiac failure or fluid overload. If more than one component occurred on the same day, the patient was counted under the first event according to the following hierarchy: acute IPF exacerbation followed by death.

Outcome measures

Outcome measures
Measure	Placebo n=392 Participants Patients with progressive fibrosing interstitial lung disease (PF-ILD) or progressive pulmonary fibrosis (PPF), other than idiopathic pulmonary fibrosis (IPF), were administered placebo matching nerandomilast, taken orally as film-coated tablets twice daily, in the morning and in the evening for an initial 52 weeks, followed by a variable duration till end of trial.	Nerandomilast 9 mg n=393 Participants Patients with progressive fibrosing interstitial lung disease (PF-ILD) or progressive pulmonary fibrosis (PPF), other than idiopathic pulmonary fibrosis (IPF), were administered 9 milligrams (mg) nerandomilast, taken orally as film-coated tablets twice daily (18 mg total), in the morning and in the evening for an initial 52 weeks, followed by a variable duration till end of trial.	Nerandomilast 18 mg n=391 Participants Patients with progressive fibrosing interstitial lung disease (PF-ILD) or progressive pulmonary fibrosis (PPF), other than idiopathic pulmonary fibrosis (IPF), were administered 18 mg nerandomilast, taken orally as film-coated tablets twice daily (36 mg total), in the morning and in the evening for an initial 52 weeks, followed by a variable duration till end of trial.
Time to First Acute ILD Exacerbation or Death Over the Duration of the Trial Death	40 Participants	24 Participants	24 Participants
Time to First Acute ILD Exacerbation or Death Over the Duration of the Trial Acute ILD exacerbation	57 Participants	46 Participants	35 Participants

SECONDARY outcome

Timeframe: From first administration of trial drug (Nerandomilast or Placebo) till end of study, up to 26.2 months.

Time to hospitalisation for respiratory cause or death over the duration of the trial is reported as the number of participants who experienced either event. Hospitalizations due to respiratory causes were recorded on a specific non-elective hospitalization CRF page. This page captured the hospitalization date, confirmation of a respiratory cause, and the primary admission diagnosis. Time to death was based either on the date of death on the adverse event (AE) report for patients with AEs leading to death or was based on the information from the vital status assessment.

Outcome measures

Outcome measures
Measure	Placebo n=392 Participants Patients with progressive fibrosing interstitial lung disease (PF-ILD) or progressive pulmonary fibrosis (PPF), other than idiopathic pulmonary fibrosis (IPF), were administered placebo matching nerandomilast, taken orally as film-coated tablets twice daily, in the morning and in the evening for an initial 52 weeks, followed by a variable duration till end of trial.	Nerandomilast 9 mg n=393 Participants Patients with progressive fibrosing interstitial lung disease (PF-ILD) or progressive pulmonary fibrosis (PPF), other than idiopathic pulmonary fibrosis (IPF), were administered 9 milligrams (mg) nerandomilast, taken orally as film-coated tablets twice daily (18 mg total), in the morning and in the evening for an initial 52 weeks, followed by a variable duration till end of trial.	Nerandomilast 18 mg n=391 Participants Patients with progressive fibrosing interstitial lung disease (PF-ILD) or progressive pulmonary fibrosis (PPF), other than idiopathic pulmonary fibrosis (IPF), were administered 18 mg nerandomilast, taken orally as film-coated tablets twice daily (36 mg total), in the morning and in the evening for an initial 52 weeks, followed by a variable duration till end of trial.
Time to Hospitalisation for Respiratory Cause or Death Over the Duration of the Trial Hospitalization for respiratory cause	113 Participants	90 Participants	94 Participants
Time to Hospitalisation for Respiratory Cause or Death Over the Duration of the Trial Death	18 Participants	13 Participants	9 Participants

SECONDARY outcome

Timeframe: From first administration of trial drug (Nerandomilast or Placebo) till end of study, up to 26.2 months.

Time to death over the duration of the trial is reported as the number of participants who died. Time to death was based either on the date of death on the AE report for patients with AEs leading to death or based on the information from the vital status assessment.

Outcome measures

Outcome measures
Measure	Placebo n=392 Participants Patients with progressive fibrosing interstitial lung disease (PF-ILD) or progressive pulmonary fibrosis (PPF), other than idiopathic pulmonary fibrosis (IPF), were administered placebo matching nerandomilast, taken orally as film-coated tablets twice daily, in the morning and in the evening for an initial 52 weeks, followed by a variable duration till end of trial.	Nerandomilast 9 mg n=393 Participants Patients with progressive fibrosing interstitial lung disease (PF-ILD) or progressive pulmonary fibrosis (PPF), other than idiopathic pulmonary fibrosis (IPF), were administered 9 milligrams (mg) nerandomilast, taken orally as film-coated tablets twice daily (18 mg total), in the morning and in the evening for an initial 52 weeks, followed by a variable duration till end of trial.	Nerandomilast 18 mg n=391 Participants Patients with progressive fibrosing interstitial lung disease (PF-ILD) or progressive pulmonary fibrosis (PPF), other than idiopathic pulmonary fibrosis (IPF), were administered 18 mg nerandomilast, taken orally as film-coated tablets twice daily (36 mg total), in the morning and in the evening for an initial 52 weeks, followed by a variable duration till end of trial.
Time to Death Over the Duration of the Trial	64 Participants	36 Participants	34 Participants

SECONDARY outcome

Timeframe: The MMRM model is a longitudinal analysis, and it incorporated FVC % predicted change from baseline at Week 1, Week 2, Week 6, Week 12, Week 18, Week 26, Week 36, Week 44 and Week 52. Data presented is change from baseline in FVC % predicted at Week 52.

Population: Full Analysis Set (FAS): This patient set included all randomized patients who received at least one dose of study drug. The FAS was used for baseline demographics and characteristics, protocol deviations, and all efficacy analyses, in which patients were analyzed as their randomized treatment group. Only participants with baseline measurement and at least one post-baseline measurement were included.

Absolute change from baseline in forced vital capacity (FVC) percent (%) predicted at Week 52 is reported. Analysis was based on a Mixed Model for Repeated Measures (MMRM), with fixed, categorical effects of treatment at each visit, baseline antifibrotic therapy at each visit, baseline HRCT pattern at each visit, the fixed continuous effects of baseline FVC \[% pred\] at each visit and unstructured covariance for repeated measures. Baseline antifibrotic therapy and HRCT pattern as entered in the CRF pages were used as covariates.

Outcome measures

Outcome measures
Measure	Placebo n=360 Participants Patients with progressive fibrosing interstitial lung disease (PF-ILD) or progressive pulmonary fibrosis (PPF), other than idiopathic pulmonary fibrosis (IPF), were administered placebo matching nerandomilast, taken orally as film-coated tablets twice daily, in the morning and in the evening for an initial 52 weeks, followed by a variable duration till end of trial.	Nerandomilast 9 mg n=348 Participants Patients with progressive fibrosing interstitial lung disease (PF-ILD) or progressive pulmonary fibrosis (PPF), other than idiopathic pulmonary fibrosis (IPF), were administered 9 milligrams (mg) nerandomilast, taken orally as film-coated tablets twice daily (18 mg total), in the morning and in the evening for an initial 52 weeks, followed by a variable duration till end of trial.	Nerandomilast 18 mg n=344 Participants Patients with progressive fibrosing interstitial lung disease (PF-ILD) or progressive pulmonary fibrosis (PPF), other than idiopathic pulmonary fibrosis (IPF), were administered 18 mg nerandomilast, taken orally as film-coated tablets twice daily (36 mg total), in the morning and in the evening for an initial 52 weeks, followed by a variable duration till end of trial.
Absolute Change From Baseline in Forced Vital Capacity (FVC) Percent (%) Predicted at Week 52	-4.88 FVC percent predicted Interval -5.61 to -4.15	-2.69 FVC percent predicted Interval -3.43 to -1.95	-2.94 FVC percent predicted Interval -3.68 to -2.19

SECONDARY outcome

Timeframe: From first administration of trial drug (Nerandomilast or Placebo) till end of study, up to 26.2 months.

Population: Full Analysis Set (FAS): This patient set includes all randomised patients who received at least one dose of study drug. The FAS was used for baseline demographics and characteristics, protocol deviations, and all efficacy analyses, in which patients were analysed as their randomised treatment group.

The time to absolute decline of more than 10% from baseline in forced vital capacity (FVC) percent predicted, or death, over the duration of the trial is reported as the number of participants who experienced either event. If multiple components occurred on the day of first event, then the patient was only counted in the first component based on the following hierarchy: absolute decline in FVC % predicted of \> 10% followed by death.

Outcome measures

Outcome measures
Measure	Placebo n=392 Participants Patients with progressive fibrosing interstitial lung disease (PF-ILD) or progressive pulmonary fibrosis (PPF), other than idiopathic pulmonary fibrosis (IPF), were administered placebo matching nerandomilast, taken orally as film-coated tablets twice daily, in the morning and in the evening for an initial 52 weeks, followed by a variable duration till end of trial.	Nerandomilast 9 mg n=393 Participants Patients with progressive fibrosing interstitial lung disease (PF-ILD) or progressive pulmonary fibrosis (PPF), other than idiopathic pulmonary fibrosis (IPF), were administered 9 milligrams (mg) nerandomilast, taken orally as film-coated tablets twice daily (18 mg total), in the morning and in the evening for an initial 52 weeks, followed by a variable duration till end of trial.	Nerandomilast 18 mg n=391 Participants Patients with progressive fibrosing interstitial lung disease (PF-ILD) or progressive pulmonary fibrosis (PPF), other than idiopathic pulmonary fibrosis (IPF), were administered 18 mg nerandomilast, taken orally as film-coated tablets twice daily (36 mg total), in the morning and in the evening for an initial 52 weeks, followed by a variable duration till end of trial.
Time to Absolute Decline in Forced Vital Capacity (FVC) % Predicted of >10% From Baseline or Death Over the Duration of the Trial Absolute decline in FVC % predicted of > 10%	130 Participants	95 Participants	100 Participants
Time to Absolute Decline in Forced Vital Capacity (FVC) % Predicted of >10% From Baseline or Death Over the Duration of the Trial Death	39 Participants	30 Participants	24 Participants

SECONDARY outcome

Timeframe: The MMRM model is a longitudinal analysis and it incorporated DLCO measurements from baseline (Week -8 to Week -1) and Week 12, Week 26, and Week 52. The data represent the adjusted Least Square Means for change from baseline at Week 52.

Population: Full Analysis Set (FAS): This patient set included all randomized patients who received at least one dose of study drug. The FAS was used for baseline demographics and characteristics, protocol deviations, and all efficacy analyses, in which patients were analyzed as their randomized treatment group. Only participants with baseline measurement and at least one post-baseline measurement were included.

The absolute change from baseline in Diffusing Capacity of the Lungs for Carbon Monoxide percent predicted (corrected for hemoglobin, Hb) at Week 52 is reported.. Analysis was based on a Mixed Model for Repeated Measures (MMRM), with fixed, categorical effects of treatment at each visit, baseline antifibrotic therapy at each visit, baseline HRCT pattern at each visit, the fixed continuous effects of baseline DLCO \[% pred\] at each visit and unstructured covariance for repeated measures. Baseline antifibrotic therapy and HRCT pattern as entered in the CRF pages were used as covariates.

Outcome measures

Outcome measures
Measure	Placebo n=321 Participants Patients with progressive fibrosing interstitial lung disease (PF-ILD) or progressive pulmonary fibrosis (PPF), other than idiopathic pulmonary fibrosis (IPF), were administered placebo matching nerandomilast, taken orally as film-coated tablets twice daily, in the morning and in the evening for an initial 52 weeks, followed by a variable duration till end of trial.	Nerandomilast 9 mg n=316 Participants Patients with progressive fibrosing interstitial lung disease (PF-ILD) or progressive pulmonary fibrosis (PPF), other than idiopathic pulmonary fibrosis (IPF), were administered 9 milligrams (mg) nerandomilast, taken orally as film-coated tablets twice daily (18 mg total), in the morning and in the evening for an initial 52 weeks, followed by a variable duration till end of trial.	Nerandomilast 18 mg n=311 Participants Patients with progressive fibrosing interstitial lung disease (PF-ILD) or progressive pulmonary fibrosis (PPF), other than idiopathic pulmonary fibrosis (IPF), were administered 18 mg nerandomilast, taken orally as film-coated tablets twice daily (36 mg total), in the morning and in the evening for an initial 52 weeks, followed by a variable duration till end of trial.
Absolute Change From Baseline in Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO) % Predicted (Corrected for Hb) at Week 52	-2.48 DLCO percent (%) predicted Interval -3.89 to -1.07	-3.38 DLCO percent (%) predicted Interval -4.8 to -1.96	-2.97 DLCO percent (%) predicted Interval -4.4 to -1.53

SECONDARY outcome

Timeframe: From first administration of trial drug (Nerandomilast or Placebo) till end of study, up to 26.2 months.

Time to absolute decline in Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO) percentage predicted by more than 15% from baseline or death, measured over the duration of the trial is reported as the number of participants who experienced either event. The Predicted DLCO value was corrected for hemoglobin (Hb). If more than one component occurred on the same day, the patient was counted under the first event according to the hierarchy: Absolute decline in DLCO % predicted of \> 15%, followed by Death.

Outcome measures

Outcome measures
Measure	Placebo n=392 Participants Patients with progressive fibrosing interstitial lung disease (PF-ILD) or progressive pulmonary fibrosis (PPF), other than idiopathic pulmonary fibrosis (IPF), were administered placebo matching nerandomilast, taken orally as film-coated tablets twice daily, in the morning and in the evening for an initial 52 weeks, followed by a variable duration till end of trial.	Nerandomilast 9 mg n=393 Participants Patients with progressive fibrosing interstitial lung disease (PF-ILD) or progressive pulmonary fibrosis (PPF), other than idiopathic pulmonary fibrosis (IPF), were administered 9 milligrams (mg) nerandomilast, taken orally as film-coated tablets twice daily (18 mg total), in the morning and in the evening for an initial 52 weeks, followed by a variable duration till end of trial.	Nerandomilast 18 mg n=391 Participants Patients with progressive fibrosing interstitial lung disease (PF-ILD) or progressive pulmonary fibrosis (PPF), other than idiopathic pulmonary fibrosis (IPF), were administered 18 mg nerandomilast, taken orally as film-coated tablets twice daily (36 mg total), in the morning and in the evening for an initial 52 weeks, followed by a variable duration till end of trial.
Time to Absolute Decline in Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO) Percentage Predicted by More Than 15% From Baseline or Death, Measured Over the Duration of the Trial Absolute decline in DLCO % predicted of > 15%	49 Participants	53 Participants	52 Participants
Time to Absolute Decline in Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO) Percentage Predicted by More Than 15% From Baseline or Death, Measured Over the Duration of the Trial Death	58 Participants	35 Participants	32 Participants

SECONDARY outcome

Timeframe: The MMRM model is a longitudinal analysis and it incorporated L-PF measurements from baseline (Week -8 to Week -1) and Week 12, Week 26, Week 36, Week 44 and Week 52. The data represent the adjusted Least Square Means for change from baseline at Week 52.

Population: Full Analysis Set (FAS): This patient set included all randomized patients who received at least one dose of study drug. The FAS was used for baseline demographics and characteristics, protocol deviations, and all efficacy analyses, in which patients were analyzed as their randomized treatment group. Only participants with baseline measurement and at least one post-baseline measurement were included.

The absolute change from baseline in Living with Pulmonary Fibrosis (L-PF) Symptoms Dyspnea domain score at Week 52 is reported. The Living with Pulmonary Fibrosis (L-PF) questionnaire is a 44-item tool consisting of two modules: Symptoms (23 items) and Impacts (21 items). The Symptoms module yields three domain scores: Dyspnoea, Cough, and Fatigue, as well as a Total Symptoms score. Scoring is based on the mean of item ratings within each domain, multiplied by 100. Scores range from 0 to 100, with higher scores indicating greater impairment. This endpoint was analyzed using a Mixed Model for Repeated Measures (MMRM). The model included fixed effects for treatment, baseline antifibrotic therapy, baseline HRCT pattern, and fixed continuous effect of baseline L-PF dyspnea score at each visit, with an unstructured covariance for repeated measures. Baseline antifibrotic therapy and HRCT pattern as entered in the CRF pages were covariates.

Outcome measures

Outcome measures
Measure	Placebo n=331 Participants Patients with progressive fibrosing interstitial lung disease (PF-ILD) or progressive pulmonary fibrosis (PPF), other than idiopathic pulmonary fibrosis (IPF), were administered placebo matching nerandomilast, taken orally as film-coated tablets twice daily, in the morning and in the evening for an initial 52 weeks, followed by a variable duration till end of trial.	Nerandomilast 9 mg n=329 Participants Patients with progressive fibrosing interstitial lung disease (PF-ILD) or progressive pulmonary fibrosis (PPF), other than idiopathic pulmonary fibrosis (IPF), were administered 9 milligrams (mg) nerandomilast, taken orally as film-coated tablets twice daily (18 mg total), in the morning and in the evening for an initial 52 weeks, followed by a variable duration till end of trial.	Nerandomilast 18 mg n=328 Participants Patients with progressive fibrosing interstitial lung disease (PF-ILD) or progressive pulmonary fibrosis (PPF), other than idiopathic pulmonary fibrosis (IPF), were administered 18 mg nerandomilast, taken orally as film-coated tablets twice daily (36 mg total), in the morning and in the evening for an initial 52 weeks, followed by a variable duration till end of trial.
Absolute Change From Baseline in Living With Pulmonary Fibrosis (L-PF) Symptoms Dyspnea Domain Score at Week 52	5.75 Score on a scale Interval 4.04 to 7.46	4.87 Score on a scale Interval 3.15 to 6.58	4.48 Score on a scale Interval 2.76 to 6.2

SECONDARY outcome

Population: Full Analysis Set (FAS): This patient set included all randomized patients who received at least one dose of study drug. The FAS was used for baseline demographics and characteristics, protocol deviations, and all efficacy analyses, in which patients were analyzed as their randomized treatment group. Only participants with baseline measurement and at least one post-baseline measurement were included.

The absolute change from baseline in the L-PF Cough domain score at Week 52 is reported. The Living with Pulmonary Fibrosis (L-PF) questionnaire is a 44-item tool consisting of two modules: Symptoms (23 items) and Impacts (21 items). The Symptoms module yields three domain scores: Dyspnea, Cough, and Fatigue, as well as a Total Symptoms score. Scoring is based on the mean of item ratings within each domain, multiplied by 100. Scores range from 0 to 100, with higher scores indicating greater impairment. This endpoint was analyzed using a Mixed Model for Repeated Measures (MMRM). The model included fixed effects for treatment, baseline antifibrotic therapy, baseline HRCT pattern, and fixed continuous effect of baseline L-PF dyspnea score at each visit, with an unstructured covariance for repeated measures. Baseline antifibrotic therapy and HRCT pattern as entered in the CRF pages were covariates.

Outcome measures

Outcome measures
Measure	Placebo n=331 Participants Patients with progressive fibrosing interstitial lung disease (PF-ILD) or progressive pulmonary fibrosis (PPF), other than idiopathic pulmonary fibrosis (IPF), were administered placebo matching nerandomilast, taken orally as film-coated tablets twice daily, in the morning and in the evening for an initial 52 weeks, followed by a variable duration till end of trial.	Nerandomilast 9 mg n=328 Participants Patients with progressive fibrosing interstitial lung disease (PF-ILD) or progressive pulmonary fibrosis (PPF), other than idiopathic pulmonary fibrosis (IPF), were administered 9 milligrams (mg) nerandomilast, taken orally as film-coated tablets twice daily (18 mg total), in the morning and in the evening for an initial 52 weeks, followed by a variable duration till end of trial.	Nerandomilast 18 mg n=328 Participants Patients with progressive fibrosing interstitial lung disease (PF-ILD) or progressive pulmonary fibrosis (PPF), other than idiopathic pulmonary fibrosis (IPF), were administered 18 mg nerandomilast, taken orally as film-coated tablets twice daily (36 mg total), in the morning and in the evening for an initial 52 weeks, followed by a variable duration till end of trial.
Absolute Change From Baseline in Living With Pulmonary Fibrosis (L-PF) Symptoms Cough Domain Score at Week 52	3.05 Score on a scale Interval 0.79 to 5.31	1.17 Score on a scale Interval -1.09 to 3.44	3.19 Score on a scale Interval 0.92 to 5.46

SECONDARY outcome

Population: Full Analysis Set (FAS): This patient set included all randomized patients who received at least one dose of study drug. The FAS was used for baseline demographics and characteristics, protocol deviations, and all efficacy analyses, in which patients were analyzed as their randomized treatment group. Only participants with baseline measurement and at least one post-baseline measurement were included.

The absolute change from baseline in the L-PF Fatigue domain score at Week 52 is reported. The Living with Pulmonary Fibrosis (L-PF) questionnaire is a 44-item tool consisting of two modules: Symptoms (23 items) and Impacts (21 items). The Symptoms module yields three domain scores: Dyspnea, Cough, and Fatigue, as well as a Total Symptoms score. Scoring is based on the mean of item ratings within each domain, multiplied by 100. Scores range from 0 to 100, with higher scores indicating greater impairment. This endpoint was analyzed using a Mixed Model for Repeated Measures (MMRM). The model included fixed effects for treatment, baseline antifibrotic therapy, and baseline HRCT pattern at each visit, and fixed continuous effect of baseline L-PF Fatigue score at each visit, with an unstructured covariance for repeated measures. Baseline antifibrotic therapy and HRCT pattern as entered in the CRF pages were covariates.

Outcome measures

Outcome measures
Measure	Placebo n=331 Participants Patients with progressive fibrosing interstitial lung disease (PF-ILD) or progressive pulmonary fibrosis (PPF), other than idiopathic pulmonary fibrosis (IPF), were administered placebo matching nerandomilast, taken orally as film-coated tablets twice daily, in the morning and in the evening for an initial 52 weeks, followed by a variable duration till end of trial.	Nerandomilast 9 mg n=329 Participants Patients with progressive fibrosing interstitial lung disease (PF-ILD) or progressive pulmonary fibrosis (PPF), other than idiopathic pulmonary fibrosis (IPF), were administered 9 milligrams (mg) nerandomilast, taken orally as film-coated tablets twice daily (18 mg total), in the morning and in the evening for an initial 52 weeks, followed by a variable duration till end of trial.	Nerandomilast 18 mg n=327 Participants Patients with progressive fibrosing interstitial lung disease (PF-ILD) or progressive pulmonary fibrosis (PPF), other than idiopathic pulmonary fibrosis (IPF), were administered 18 mg nerandomilast, taken orally as film-coated tablets twice daily (36 mg total), in the morning and in the evening for an initial 52 weeks, followed by a variable duration till end of trial.
Absolute Change From Baseline in Living With Pulmonary Fibrosis (L-PF) Symptoms Fatigue Domain Score at Week 52	2.95 Score on a scale Interval 1.18 to 4.73	3.01 Score on a scale Interval 1.23 to 4.78	3.89 Score on a scale Interval 2.11 to 5.68

Adverse Events

Placebo

Serious events: 198 serious events

Other events: 320 other events

Deaths: 64 deaths

Nerandomilast 9 mg

Serious events: 174 serious events

Other events: 324 other events

Deaths: 36 deaths

Nerandomilast 18 mg

Serious events: 182 serious events

Other events: 333 other events

Deaths: 34 deaths

Serious adverse events

Other adverse events

Additional Information

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Results disclosure agreements

Principal investigator is a sponsor employee Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
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Restriction type: OTHER