Idiopathic Pulmonary Fibrosis
Conditions
Brief summary
This study is open to adults with a lung disease called Idiopathic Pulmonary Fibrosis (IPF). People can join the study if they are 40 years or older. If they already take nintedanib or pirfenidone for their IPF, they can continue treatment throughout the study. The purpose of this study is to find out whether a medicine called BI 1015550 helps people with IPF. Participants are put into 3 groups randomly, which means by chance. Participants in 2 groups take different doses of BI 1015550 as tablets twice a day. Participants in the placebo group take placebo tablets twice a day. Placebo tablets look like BI 1015550 tablets but do not contain any medicine. Participants are in the study for up to two and a half years. During the first year, they visit the study site 10 times. Afterwards, they visit the study site every 3 months. The doctors regularly test participants' lung function. The results of the lung function tests are compared between the groups. The doctors also regularly check participants' health and take note of any unwanted effects.
Interventions
DRUGBI 1015550
Participants received film-coated nerandomilast tablets orally twice daily at doses of either 9 mg or 18 mg, with each dose administered at least 12 hours apart and taken with 250 mL of water.
DRUGPlacebo
Participants received placebo matching 9 mg or 18 mg nerandomilast film-coated tablets orally twice daily, with doses given at least 12 hours apart and each taken with 250 mL of water.
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients ≥40 years old at the time of signed informed consent. 2. Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial. 3. Diagnosis of Idiopathic Pulmonary Fibrosis (IPF). 4. Patients may be either: * on a stable therapy\* with nintedanib or pirfenidone for at least 12 weeks prior to Visit 1 and during screening and are planning to stay on this background treatment after randomization. Combination of nintedanib plus pirfenidone is not allowed. (\*stable therapy is defined as the individually and general tolerated regimen of either nintedanib or pirfenidone (no dose changes) for at least 12 weeks). * not on a treatment with nintedanib or pirfenidone for at least 8 weeks prior to Visit 1 and during the screening period (e.g. either Antifibrotic (AF)-treatment naïve or previously discontinued) and do not plan to start or re-start antifibrotic treatment. 5. Forced Vital Capacity (FVC) ≥45% of predicted normal at Visit 1. 6. Diffusing Capacity (of Lung) for Carbon Monoxide (DLCO) ≥25% of predicted normal corrected for hemoglobin (Hb) at Visit 1. 7. Women of childbearing potential (WOCBP) must be ready and able to use highly effective methods of birth control. WOCBP taking oral contraceptives (OCs) also have to use one barrier method.
Exclusion criteria
1. Prebronchodilator Forced Expiratory Volume in 1 second (FEV1)/Forced vital capacity (FVC) \<0.7 at Visit 1. 2. In the opinion of the Investigator, other clinically significant pulmonary abnormalities. 3. Acute Idiopathic Pulmonary Fibrosis (IPF) exacerbation within 3 months prior to Visit 1 and/or during the screening period (investigator-determined). 4. Relevant chronic or acute infections including human immunodeficiency virus (HIV) and viral hepatitis. 5. Confirmed infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) not fully recovered according to investigator judgement within the 4 weeks prior to randomization (Visit 2). 6. Major surgery (major according to the investigator's assessment) performed within 6 weeks prior to Visit 2 or planned during the trial period, e.g. hip replacement. Registration on lung transplantation list would not be considered as planned major surgery. 7. Any documented active or suspected malignancy or history of malignancy within 5 years prior to Visit 1, except appropriately treated basal cell carcinoma of the skin, in situ squamous cell carcinoma of the skin or in situ carcinoma of uterine cervix. 8. Aspartate aminotransferase (AST) or Alanine Aminotransferase (ALT) \>2.5 x Upper limit of normal (ULN) or total Bilirubin \>1.5 x ULN at Visit 1. Further
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change From Baseline in Forced Vital Capacity (FVC) [mL] at Week 52 | The MMRM model is a longitudinal analysis, and it incorporated FVC measurements from baseline (Week -8 to Week -1) and Week 2, Week 6, Week 12, Week 18, Week 26, Week 36, Week 44 and Week 52. The data represent the Least Squares Mean at Week 52 | The absolute change from baseline in Forced Vital Capacity (FVC) \[mL\] at Week 52 is reported. The absolute change from baseline in forced vital capacity (FVC) at Week 52 was analyzed using a restricted maximum likelihood (REML)-based mixed model with repeated measures (MMRM). The model included fixed categorical effects of treatment and baseline antifibrotic use at each visit, as well as the continuous effect of baseline FVC. Visit was treated as a repeated measure, with an unstructured covariance structure for within-patient variability. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to First Acute IPF Exacerbation or Death Over the Duration of the Trial | From first administration of any trial drug (Nerandomilast or Placebo) up to 22.9 months. | The time to first acute IPF exacerbation or death during the trial is reported as the number of participants who experienced either event. Acute IPF is defined as 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 of less than 1 month's duration. Computed tomography showing new bilateral ground-glass opacity and/or consolidation superimposed on a background pattern consistent with IPF. 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. |
| Time to Hospitalization for Respiratory Cause or Death Over the Duration of the Trial | From first administration of any trial drug (Nerandomilast or Placebo) up to 22.9 months. | Time to hospitalization 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. If more than one component occurred on the same day, the patient was counted under the first event according to the hierarchy: hospitalization for respiratory cause, followed by death. |
| Time to Absolute Decline in Forced Vital Capacity (FVC) % Predicted of >10% From Baseline or Death Over the Duration of the Trial | From first administration of any trial drug (Nerandomilast or Placebo) up to 22.9 months. | 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 more than one component occurred on the same day, the patient was counted under the first event according to the hierarchy; Absolute decline in FVC % predicted of \> 10% followed by death. |
| 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 | From first administration of any trial drug (Nerandomilast or Placebo) up to 22.9 months. | The time to absolute decline of more than 15% from baseline in diffusing capacity of the lungs for carbon monoxide (DLCO) percent predicted, or death, over the duration of the trial is reported as the number of participants who experienced either event. 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. |
| Time to Death Over the Duration of the Trial | From first administration of any trial drug (Nerandomilast or Placebo) up to 22.9 months. | Time to death over the duration of the trial is reported as the number of participants who died. Time to death will be based either on the date of death on the AE report for patients with AEs leading to death or will be based on the information from the vital status assessment. |
| Key Secondary Endpoint: Time to the First Occurrence of Any of the Components of the Composite Endpoint: Time to First Acute IPF Exacerbation, First Hospitalization for Respiratory Cause, or Death (Whichever Occurs First) Over the Duration of the Trial | From first administration of any trial drug (Nerandomilast or Placebo) up to 22.9 months. | Time to the first occurrence of any component of the composite endpoint-acute IPF exacerbation, hospitalization for a respiratory cause, or death (whichever occurred first)-is reported as the number of participants who experienced one or more of these events during the trial. Acute IPF is defined as 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 of less than 1 month's duration. Computed tomography showing new bilateral ground-glass opacity and/or consolidation superimposed on a background pattern consistent with IPF. 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, hospitalization, death. |
| Absolute Change From Baseline in Living With Pulmonary Fibrosis (L-PF) Symptoms Cough Domain Score at Week 52 | 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 Least Squares Mean at Week 52. | The absolute change from baseline in the L-PF Cough domain score at Week 52 is reported. This endpoint was analyzed using a Mixed Model for Repeated Measures (MMRM). The model included fixed effects for treatment, baseline antifibrotic therapy, and baseline L-PF Cough score at each visit, with an unstructured covariance matrix for repeated measures. 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. |
| Absolute Change From Baseline in Living With Pulmonary Fibrosis (L-PF) Symptoms Fatigue Domain Score at Week 52 | 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 Least Squares Mean at Week 52. | The absolute change from baseline in the Living with Pulmonary Fibrosis (L-PF) Fatigue domain score at Week 52 is reported. The analysis used a mixed model for repeated measures (MMRM) with fixed categorical effects for treatment, baseline antifibrotic (AF) therapy, and the fixed continuous effect of baseline L-PF score. Covariance was unstructured. Baseline AF therapy was a covariate. 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. |
| Absolute Change From Baseline in Forced Vital Capacity Percent Predicted at Week 52 | The MMRM model is a longitudinal analysis, and it incorporated FVC measurements from baseline (Week -8 to Week -1) and Week 1, Week 2, Week 6, Week 12, Week 18, Week 26, Week 36, Week 44 and Week 52. The data represent the Least Squares Mean at Week 52. | The absolute change from baseline in Forced Vital Capacity percent predicted at Week 52 is reported. Analysis was based on a Mixed Model for Repeated Measures (MMRM), which included fixed, categorical effects of treatment at each visit, baseline use of antifibrotic therapy at each visit, and the fixed continuous effects of baseline forced vital capacity (FVC) percentage predicted at each visit. An unstructured covariance structure was used to model repeated measures within patients. Baseline use of antifibrotic therapy, as recorded in the concomitant medication case report form (CRF) page, was included as a covariate. |
| Absolute Change From Baseline in Diffusing Capacity of the Lungs for Carbon Monoxide Percent Predicted at Week 52 | 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 Least Squares Mean at Week 52. | The absolute change from baseline in Diffusing Capacity of the Lungs for Carbon Monoxide percent predicted at Week 52 is reported. The analysis was based on a Mixed Model for Repeated Measures (MMRM), which included fixed, categorical effects of treatment at each visit, baseline use of antifibrotic therapy at each visit, and the fixed continuous effects of baseline diffusing capacity of the lungs for carbon monoxide (DLCO) percentage predicted at each visit. An unstructured covariance structure was used to model repeated measures within patients. Baseline use of antifibrotic therapy, as recorded in the concomitant medication case report form (CRF) page, was included as a covariate. |
| Absolute Change From Baseline in Living With Pulmonary Fibrosis (L-PF) Symptoms Dyspnea Domain Score at Week 52 | 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 Least Squares Mean at Week 52. | The absolute change from baseline in the Living with Pulmonary Fibrosis (L-PF) Symptoms Dyspnea domain score at Week 52 is reported. This endpoint was analyzed using a Mixed Model for Repeated Measures (MMRM). The model included fixed effects for treatment, baseline use of antifibrotic therapy, and baseline dyspnea score at each visit, with an unstructured covariance structure to model repeated measures. 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. |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, China, Croatia, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Japan, Malaysia, Mexico, Netherlands, New Zealand, Norway, Poland, Portugal, Puerto Rico, Singapore, South Africa, South Korea, Spain, Sweden, Switzerland, Taiwan, Thailand, United Kingdom, United States
Participant flow
Recruitment details
This was a randomized, double-blind, placebo-controlled, multi-centre, Phase III trial evaluating the efficacy, safety, and tolerability of nerandomilast (BI 1015550) 9 mg and 18 mg bid versus placebo in patients with IPF. The trial included two parts: Treatment Period A lasted up to 52 weeks post-randomisation, followed by Treatment Period B with continued blinded treatment for a variable duration beyond 52 weeks.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo matching 9 mg or 18 mg nerandomilast orally twice daily, with doses given at least 12 hours apart and each taken with 250 mL of water. | 393 |
| Nerandomilast 9 mg BID Participants received 9 mg film-coated nerandomilast tablets orally twice daily, with doses administered at least 12 hours apart, each taken with 250 mL of water. | 392 |
| Nerandomilast 18 mg BID Participants received 18 mg film-coated nerandomilast tablets orally twice daily, with doses administered at least 12 hours apart, each taken with 250 mL of water. | 392 |
| Total | 1,177 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 52 | 52 | 64 |
| Overall Study | Lack of Efficacy | 1 | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 | 1 |
| Overall Study | No reason stated by the participants | 23 | 22 | 16 |
| Overall Study | Protocol Violation | 1 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 23 | 18 | 12 |
Baseline characteristics
| Characteristic | Total | Nerandomilast 18 mg BID | Nerandomilast 9 mg BID | Placebo |
|---|---|---|---|---|
| Age, Continuous | 70.2 Years STANDARD_DEVIATION 7.7 | 70.3 Years STANDARD_DEVIATION 7.8 | 70.5 Years STANDARD_DEVIATION 7.8 | 69.9 Years STANDARD_DEVIATION 7.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 95 Participants | 44 Participants | 23 Participants | 28 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1082 Participants | 348 Participants | 369 Participants | 365 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Forced Vital Capacity (FVC) at baseline | 2842.8 Milliliters (mL) STANDARD_DEVIATION 781.1 | 2827.3 Milliliters (mL) STANDARD_DEVIATION 758 | 2837.2 Milliliters (mL) STANDARD_DEVIATION 781.4 | 2863.9 Milliliters (mL) STANDARD_DEVIATION 804.6 |
| Race (NIH/OMB) American Indian or Alaska Native | 5 Participants | 2 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 367 Participants | 130 Participants | 121 Participants | 116 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 797 Participants | 258 Participants | 266 Participants | 273 Participants |
| Sex: Female, Male Female | 200 Participants | 69 Participants | 75 Participants | 56 Participants |
| Sex: Female, Male Male | 977 Participants | 323 Participants | 317 Participants | 337 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 42 / 393 | 36 / 392 | 26 / 392 |
| other Total, other adverse events | 316 / 393 | 319 / 392 | 337 / 392 |
| serious Total, serious adverse events | 181 / 393 | 159 / 392 | 165 / 392 |
Outcome results
Primary
Absolute Change From Baseline in Forced Vital Capacity (FVC) [mL] at Week 52
The absolute change from baseline in Forced Vital Capacity (FVC) \[mL\] at Week 52 is reported. The absolute change from baseline in forced vital capacity (FVC) at Week 52 was analyzed using a restricted maximum likelihood (REML)-based mixed model with repeated measures (MMRM). The model included fixed categorical effects of treatment and baseline antifibrotic use at each visit, as well as the continuous effect of baseline FVC. Visit was treated as a repeated measure, with an unstructured covariance structure for within-patient variability.
Time frame: The MMRM model is a longitudinal analysis, and it incorporated FVC measurements from baseline (Week -8 to Week -1) and Week 2, Week 6, Week 12, Week 18, Week 26, Week 36, Week 44 and Week 52. The data represent the Least Squares Mean at Week 52
Population: Full Analysis Set (FAS): This patient set includes all randomized patients who received at least one dose of study drug. only patients with baseline measurement and at least one post-baseline measurement are included.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Absolute Change From Baseline in Forced Vital Capacity (FVC) [mL] at Week 52 | -183.48 Milliliters (mL) |
| Nerandomilast 9 mg BID | Absolute Change From Baseline in Forced Vital Capacity (FVC) [mL] at Week 52 | -138.60 Milliliters (mL) |
| Nerandomilast 18 mg BID | Absolute Change From Baseline in Forced Vital Capacity (FVC) [mL] at Week 52 | -114.65 Milliliters (mL) |
Comparison: Based on a Mixed Model for Repeated Measures (MMRM), which included fixed, categorical effects of treatment at each visit, baseline use of antifibrotic therapy at each visit, and fixed continuous effects of baseline forced vital capacity (FVC) in milliliters at each visit. Patients were treated as a random effect. Visit was treated as the repeated measure, and an unstructured covariance structure was used to model the within-patient measurements.p-value: 0.022295% CI: [6.44, 83.33]Mixed Models Analysis
Comparison: Based on a Mixed Model for Repeated Measures (MMRM), which included fixed, categorical effects of treatment at each visit, baseline use of antifibrotic therapy at each visit, and fixed continuous effects of baseline forced vital capacity (FVC) in milliliters at each visit. Patients were treated as a random effect. Visit was treated as the repeated measure, and an unstructured covariance structure was used to model the within-patient measurements.p-value: 0.000595% CI: [30.26, 107.39]Mixed Models Analysis
Secondary
Absolute Change From Baseline in Diffusing Capacity of the Lungs for Carbon Monoxide Percent Predicted at Week 52
The absolute change from baseline in Diffusing Capacity of the Lungs for Carbon Monoxide percent predicted at Week 52 is reported. The analysis was based on a Mixed Model for Repeated Measures (MMRM), which included fixed, categorical effects of treatment at each visit, baseline use of antifibrotic therapy at each visit, and the fixed continuous effects of baseline diffusing capacity of the lungs for carbon monoxide (DLCO) percentage predicted at each visit. An unstructured covariance structure was used to model repeated measures within patients. Baseline use of antifibrotic therapy, as recorded in the concomitant medication case report form (CRF) page, was included as a covariate.
Time frame: 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 Least Squares Mean at Week 52.
Population: Full Analysis Set (FAS): This patient set includes all randomized patients who received at least one dose of study drug. Only patients with baseline measurement and at least one post-baseline measurement are included.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Absolute Change From Baseline in Diffusing Capacity of the Lungs for Carbon Monoxide Percent Predicted at Week 52 | -6.14 DLCO percent predicted |
| Nerandomilast 9 mg BID | Absolute Change From Baseline in Diffusing Capacity of the Lungs for Carbon Monoxide Percent Predicted at Week 52 | -3.66 DLCO percent predicted |
| Nerandomilast 18 mg BID | Absolute Change From Baseline in Diffusing Capacity of the Lungs for Carbon Monoxide Percent Predicted at Week 52 | -4.47 DLCO percent predicted |
Comparison: Based on a Mixed Model for Repeated Measures (MMRM), which included fixed, categorical effects of treatment, baseline use of antifibrotic therapy, and the fixed continuous effects of baseline diffusing capacity of the lungs for carbon monoxide (DLCO) percentage predicted at each visit. An unstructured covariance structure was used to model repeated measures within patients.~Baseline use of antifibrotic therapy, as recorded in the concomitant medication CRF page, was included as a covariate.p-value: 0.004295% CI: [0.79, 4.19]Mixed Models Analysis
Comparison: Based on a Mixed Model for Repeated Measures (MMRM), which included fixed, categorical effects of treatment, baseline use of antifibrotic therapy, and the fixed continuous effects of baseline diffusing capacity of the lungs for carbon monoxide (DLCO) percentage predicted at each visit. An unstructured covariance structure was used to model repeated measures within patients.~Baseline use of antifibrotic therapy, as recorded in the concomitant medication CRF page, was included as a covariate.p-value: 0.05395% CI: [-0.02, 3.37]Mixed Models Analysis
Secondary
Absolute Change From Baseline in Forced Vital Capacity Percent Predicted at Week 52
The absolute change from baseline in Forced Vital Capacity percent predicted at Week 52 is reported. Analysis was based on a Mixed Model for Repeated Measures (MMRM), which included fixed, categorical effects of treatment at each visit, baseline use of antifibrotic therapy at each visit, and the fixed continuous effects of baseline forced vital capacity (FVC) percentage predicted at each visit. An unstructured covariance structure was used to model repeated measures within patients. Baseline use of antifibrotic therapy, as recorded in the concomitant medication case report form (CRF) page, was included as a covariate.
Time frame: The MMRM model is a longitudinal analysis, and it incorporated FVC measurements from baseline (Week -8 to Week -1) and Week 1, Week 2, Week 6, Week 12, Week 18, Week 26, Week 36, Week 44 and Week 52. The data represent the Least Squares Mean at Week 52.
Population: Full Analysis Set (FAS): This patient set includes all randomized patients who received at least one dose of study drug. Only patients with baseline measurement and at least one post-baseline measurement are included.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Absolute Change From Baseline in Forced Vital Capacity Percent Predicted at Week 52 | -4.92 FVC percent predicted |
| Nerandomilast 9 mg BID | Absolute Change From Baseline in Forced Vital Capacity Percent Predicted at Week 52 | -3.75 FVC percent predicted |
| Nerandomilast 18 mg BID | Absolute Change From Baseline in Forced Vital Capacity Percent Predicted at Week 52 | -3.19 FVC percent predicted |
Comparison: Analysis was based on a Mixed Model for Repeated Measures (MMRM), which included fixed, categorical effects of treatment, baseline use of antifibrotic therapy, and the fixed continuous effects of baseline forced vital capacity (FVC) percentage predicted at each visit. An unstructured covariance structure was used to model repeated measures within patients.~Baseline use of antifibrotic therapy, as recorded in the concomitant medication case report form (CRF) page, was included as a covariate.p-value: 0.02895% CI: [0.13, 2.22]Mixed Models Analysis
Comparison: Analysis was based on a Mixed Model for Repeated Measures (MMRM), which included fixed, categorical effects of treatment, baseline use of antifibrotic therapy, and the fixed continuous effects of baseline forced vital capacity (FVC) percentage predicted at each visit. An unstructured covariance structure was used to model repeated measures within patients.~Baseline use of antifibrotic therapy, as recorded in the concomitant medication case report form (CRF) page, was included as a covariate.p-value: 0.001395% CI: [0.68, 2.78]Mixed Models Analysis
Secondary
Absolute Change From Baseline in Living With Pulmonary Fibrosis (L-PF) Symptoms Cough Domain Score at Week 52
The absolute change from baseline in the L-PF Cough domain score at Week 52 is reported. This endpoint was analyzed using a Mixed Model for Repeated Measures (MMRM). The model included fixed effects for treatment, baseline antifibrotic therapy, and baseline L-PF Cough score at each visit, with an unstructured covariance matrix for repeated measures. 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.
Time frame: 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 Least Squares Mean at Week 52.
Population: Full Analysis Set (FAS): This patient set includes all randomized patients who received at least one dose of study drug. Only patients with baseline measurement and at least one post-baseline measurement are included.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Absolute Change From Baseline in Living With Pulmonary Fibrosis (L-PF) Symptoms Cough Domain Score at Week 52 | 4.54 Score on a scale |
| Nerandomilast 9 mg BID | Absolute Change From Baseline in Living With Pulmonary Fibrosis (L-PF) Symptoms Cough Domain Score at Week 52 | 4.44 Score on a scale |
| Nerandomilast 18 mg BID | Absolute Change From Baseline in Living With Pulmonary Fibrosis (L-PF) Symptoms Cough Domain Score at Week 52 | 3.95 Score on a scale |
Comparison: The analysis was based on a Mixed Model for Repeated Measures (MMRM), which included fixed categorical effects for treatment group at each visit, baseline use of antifibrotic therapy at each visit, and fixed continuous effects of the baseline Living with Pulmonary Fibrosis (L-PF) Cough domain score at each visit. An unstructured covariance structure modeled repeated measures. Baseline antifibrotic use, recorded in the concomitant medication case report form (CRF), was included as a covariate.p-value: 0.944295% CI: [-2.98, 2.77]Mixed Models Analysis
Comparison: The analysis was based on a Mixed Model for Repeated Measures (MMRM), which included fixed categorical effects for treatment group at each visit, baseline use of antifibrotic therapy at each visit, and fixed continuous effects of the baseline Living with Pulmonary Fibrosis (L-PF) Cough domain score at each visit. An unstructured covariance structure modeled repeated measures. Baseline antifibrotic use, recorded in the concomitant medication case report form (CRF), was included as a covariate.p-value: 0.686295% CI: [-3.47, 2.28]Mixed Models Analysis
Secondary
Absolute Change From Baseline in Living With Pulmonary Fibrosis (L-PF) Symptoms Dyspnea Domain Score at Week 52
The absolute change from baseline in the Living with Pulmonary Fibrosis (L-PF) Symptoms Dyspnea domain score at Week 52 is reported. This endpoint was analyzed using a Mixed Model for Repeated Measures (MMRM). The model included fixed effects for treatment, baseline use of antifibrotic therapy, and baseline dyspnea score at each visit, with an unstructured covariance structure to model repeated measures. 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.
Time frame: 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 Least Squares Mean at Week 52.
Population: Full Analysis Set (FAS): This patient set includes all randomized patients who received at least one dose of study drug. Only patients with baseline measurement and at least one post-baseline measurement are included.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Absolute Change From Baseline in Living With Pulmonary Fibrosis (L-PF) Symptoms Dyspnea Domain Score at Week 52 | 7.26 Score on a scale |
| Nerandomilast 9 mg BID | Absolute Change From Baseline in Living With Pulmonary Fibrosis (L-PF) Symptoms Dyspnea Domain Score at Week 52 | 6.26 Score on a scale |
| Nerandomilast 18 mg BID | Absolute Change From Baseline in Living With Pulmonary Fibrosis (L-PF) Symptoms Dyspnea Domain Score at Week 52 | 6.63 Score on a scale |
Comparison: The analysis used a Mixed Model for Repeated Measures (MMRM) with fixed categorical effects for treatment group and baseline antifibrotic therapy at each visit, and fixed continuous effects of baseline Living with Pulmonary Fibrosis (L-PF) Dyspnea domain score. An unstructured covariance structure accounted for within-patient correlations. Baseline antifibrotic use, as recorded in the concomitant medication case report form (CRF), was included as a covariate.p-value: 0.369795% CI: [-3.2, 1.19]Mixed Models Analysis
Comparison: The analysis used a Mixed Model for Repeated Measures (MMRM) with fixed categorical effects for treatment group and baseline antifibrotic therapy at each visit, and fixed continuous effects of baseline Living with Pulmonary Fibrosis (L-PF) Dyspnea domain score. An unstructured covariance structure accounted for within-patient correlations. Baseline antifibrotic use, as recorded in the concomitant medication case report form (CRF), was included as a covariate.p-value: 0.573495% CI: [-2.83, 1.57]Mixed Models Analysis
Secondary
Absolute Change From Baseline in Living With Pulmonary Fibrosis (L-PF) Symptoms Fatigue Domain Score at Week 52
The absolute change from baseline in the Living with Pulmonary Fibrosis (L-PF) Fatigue domain score at Week 52 is reported. The analysis used a mixed model for repeated measures (MMRM) with fixed categorical effects for treatment, baseline antifibrotic (AF) therapy, and the fixed continuous effect of baseline L-PF score. Covariance was unstructured. Baseline AF therapy was a covariate. 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.
Time frame: 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 Least Squares Mean at Week 52.
Population: Full Analysis Set (FAS): This patient set includes all randomized patients who received at least one dose of study drug. Only patients with baseline measurement and at least one post-baseline measurement are included.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Absolute Change From Baseline in Living With Pulmonary Fibrosis (L-PF) Symptoms Fatigue Domain Score at Week 52 | 5.40 Score on a scale |
| Nerandomilast 9 mg BID | Absolute Change From Baseline in Living With Pulmonary Fibrosis (L-PF) Symptoms Fatigue Domain Score at Week 52 | 5.59 Score on a scale |
| Nerandomilast 18 mg BID | Absolute Change From Baseline in Living With Pulmonary Fibrosis (L-PF) Symptoms Fatigue Domain Score at Week 52 | 5.82 Score on a scale |
Comparison: The analysis was based on a Mixed Model for Repeated Measures (MMRM), which included fixed categorical effects for treatment group at each visit, baseline use of antifibrotic therapy at each visit, and fixed continuous effects of the baseline Living with Pulmonary Fibrosis (L-PF) Fatigue domain score at each visit. An unstructured covariance structure modeled repeated measures. Baseline antifibrotic use, recorded in the concomitant medication case report form (CRF), was included as a covariate.p-value: 0.875995% CI: [-2.25, 2.63]Mixed Models Analysis
Comparison: The analysis was based on a Mixed Model for Repeated Measures (MMRM), which included fixed categorical effects for treatment group at each visit, baseline use of antifibrotic therapy at each visit, and fixed continuous effects of the baseline Living with Pulmonary Fibrosis (L-PF) Fatigue domain score at each visit. An unstructured covariance structure modeled repeated measures. Baseline antifibrotic use, recorded in the concomitant medication case report form (CRF), was included as a covariate.p-value: 0.73295% CI: [-2.02, 2.87]Mixed Models Analysis
Secondary
Key Secondary Endpoint: Time to the First Occurrence of Any of the Components of the Composite Endpoint: Time to First Acute IPF Exacerbation, First Hospitalization for Respiratory Cause, or Death (Whichever Occurs First) Over the Duration of the Trial
Time to the first occurrence of any component of the composite endpoint-acute IPF exacerbation, hospitalization for a respiratory cause, or death (whichever occurred first)-is reported as the number of participants who experienced one or more of these events during the trial. Acute IPF is defined as 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 of less than 1 month's duration. Computed tomography showing new bilateral ground-glass opacity and/or consolidation superimposed on a background pattern consistent with IPF. 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, hospitalization, death.
Time frame: From first administration of any trial drug (Nerandomilast or Placebo) up to 22.9 months.
Population: Full Analysis Set (FAS): This patient set includes all randomized patients who received at least one dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Key Secondary Endpoint: Time to the First Occurrence of Any of the Components of the Composite Endpoint: Time to First Acute IPF Exacerbation, First Hospitalization for Respiratory Cause, or Death (Whichever Occurs First) Over the Duration of the Trial | Hospitalisation for respiratory cause as the first event | 49 Participants |
| Placebo | Key Secondary Endpoint: Time to the First Occurrence of Any of the Components of the Composite Endpoint: Time to First Acute IPF Exacerbation, First Hospitalization for Respiratory Cause, or Death (Whichever Occurs First) Over the Duration of the Trial | Acute IPF exacerbation as the first event | 38 Participants |
| Placebo | Key Secondary Endpoint: Time to the First Occurrence of Any of the Components of the Composite Endpoint: Time to First Acute IPF Exacerbation, First Hospitalization for Respiratory Cause, or Death (Whichever Occurs First) Over the Duration of the Trial | Death as the first event | 16 Participants |
| Nerandomilast 9 mg BID | Key Secondary Endpoint: Time to the First Occurrence of Any of the Components of the Composite Endpoint: Time to First Acute IPF Exacerbation, First Hospitalization for Respiratory Cause, or Death (Whichever Occurs First) Over the Duration of the Trial | Hospitalisation for respiratory cause as the first event | 45 Participants |
| Nerandomilast 9 mg BID | Key Secondary Endpoint: Time to the First Occurrence of Any of the Components of the Composite Endpoint: Time to First Acute IPF Exacerbation, First Hospitalization for Respiratory Cause, or Death (Whichever Occurs First) Over the Duration of the Trial | Acute IPF exacerbation as the first event | 32 Participants |
| Nerandomilast 9 mg BID | Key Secondary Endpoint: Time to the First Occurrence of Any of the Components of the Composite Endpoint: Time to First Acute IPF Exacerbation, First Hospitalization for Respiratory Cause, or Death (Whichever Occurs First) Over the Duration of the Trial | Death as the first event | 13 Participants |
| Nerandomilast 18 mg BID | Key Secondary Endpoint: Time to the First Occurrence of Any of the Components of the Composite Endpoint: Time to First Acute IPF Exacerbation, First Hospitalization for Respiratory Cause, or Death (Whichever Occurs First) Over the Duration of the Trial | Acute IPF exacerbation as the first event | 38 Participants |
| Nerandomilast 18 mg BID | Key Secondary Endpoint: Time to the First Occurrence of Any of the Components of the Composite Endpoint: Time to First Acute IPF Exacerbation, First Hospitalization for Respiratory Cause, or Death (Whichever Occurs First) Over the Duration of the Trial | Death as the first event | 8 Participants |
| Nerandomilast 18 mg BID | Key Secondary Endpoint: Time to the First Occurrence of Any of the Components of the Composite Endpoint: Time to First Acute IPF Exacerbation, First Hospitalization for Respiratory Cause, or Death (Whichever Occurs First) Over the Duration of the Trial | Hospitalisation for respiratory cause as the first event | 47 Participants |
Comparison: The hazard ratio (HR) was estimated using a Cox proportional hazards model with treatment group, baseline antifibrotic therapy use, age (continuous), baseline FVC % predicted, and baseline DLCO % predicted (hemoglobin-corrected) as covariates. Breslow's method was applied for tied event times. A two-sided p-value from the Wald test assessed the treatment effect. P-values were not adjusted for multiplicity.p-value: 0.544395% CI: [0.69, 1.22]Regression, Cox
Comparison: Based on Cox proportional hazards model including treatment, baseline antifibrotic therapy, age, baseline Forced Vital Capacity (FVC) percent predicted, and baseline Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO) percent predicted (corrected for haemoglobin) as covariates. p-values not adjusted for multiplicity.p-value: 0.951295% CI: [0.75, 1.31]Regression, Cox
Secondary
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
The time to absolute decline of more than 15% from baseline in diffusing capacity of the lungs for carbon monoxide (DLCO) percent predicted, or death, over the duration of the trial is reported as the number of participants who experienced either event. 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.
Time frame: From first administration of any trial drug (Nerandomilast or Placebo) up to 22.9 months.
Population: Full Analysis Set (FAS): This patient set includes all randomized patients who received at least one dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | 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% | 38 Participants |
| Placebo | 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 | 28 Participants |
| Nerandomilast 9 mg BID | 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% | 35 Participants |
| Nerandomilast 9 mg BID | 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 | 24 Participants |
| Nerandomilast 18 mg BID | 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% | 43 Participants |
| Nerandomilast 18 mg BID | 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 | 16 Participants |
Comparison: Analysis was performed using a Cox proportional hazards regression model that included baseline use of antifibrotic therapy (antifibrotic group vs non-antifibrotic group), age, baseline forced vital capacity (FVC) percentage predicted, baseline diffusing capacity of the lungs for carbon monoxide (DLCO) percentage predicted (corrected for hemoglobin levels), and treatment group as covariates.p-value: 0.925195% CI: [0.69, 1.41]Regression, Cox
Comparison: Analysis was performed using a Cox proportional hazards regression model that included baseline use of antifibrotic therapy (antifibrotic group vs non-antifibrotic group), age, baseline forced vital capacity (FVC) percentage predicted, baseline diffusing capacity of the lungs for carbon monoxide (DLCO) percentage predicted (corrected for hemoglobin levels), and treatment group as covariates.p-value: 0.498895% CI: [0.62, 1.26]Regression, Cox
Secondary
Time to Absolute Decline in Forced Vital Capacity (FVC) % Predicted of >10% From Baseline or Death Over the Duration of the Trial
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 more than one component occurred on the same day, the patient was counted under the first event according to the hierarchy; Absolute decline in FVC % predicted of \> 10% followed by death.
Time frame: From first administration of any trial drug (Nerandomilast or Placebo) up to 22.9 months.
Population: Full Analysis Set (FAS): This patient set includes all randomized patients who received at least one dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | 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% | 91 Participants |
| Placebo | Time to Absolute Decline in Forced Vital Capacity (FVC) % Predicted of >10% From Baseline or Death Over the Duration of the Trial | Death | 20 Participants |
| Nerandomilast 9 mg BID | 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% | 89 Participants |
| Nerandomilast 9 mg BID | Time to Absolute Decline in Forced Vital Capacity (FVC) % Predicted of >10% From Baseline or Death Over the Duration of the Trial | Death | 18 Participants |
| Nerandomilast 18 mg BID | 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% | 80 Participants |
| Nerandomilast 18 mg BID | Time to Absolute Decline in Forced Vital Capacity (FVC) % Predicted of >10% From Baseline or Death Over the Duration of the Trial | Death | 14 Participants |
Comparison: Analysis was performed using a Cox proportional hazards regression model that included baseline use of antifibrotic therapy (antifibrotic group vs non-antifibrotic group), age, baseline forced vital capacity (FVC) percentage predicted, baseline diffusing capacity of the lungs for carbon monoxide (DLCO) percentage predicted (corrected for hemoglobin levels), and treatment group as covariates.p-value: 0.769595% CI: [0.74, 1.25]Regression, Cox
Comparison: Analysis was performed using a Cox proportional hazards regression model that included baseline use of antifibrotic therapy (antifibrotic group vs non-antifibrotic group), age, baseline forced vital capacity (FVC) percentage predicted, baseline diffusing capacity of the lungs for carbon monoxide (DLCO) percentage predicted (corrected for hemoglobin levels), and treatment group as covariates.p-value: 0.206895% CI: [0.64, 1.1]Regression, Cox
Secondary
Time to Death Over the Duration of the Trial
Time to death over the duration of the trial is reported as the number of participants who died. Time to death will be based either on the date of death on the AE report for patients with AEs leading to death or will be based on the information from the vital status assessment.
Time frame: From first administration of any trial drug (Nerandomilast or Placebo) up to 22.9 months.
Population: Full Analysis Set (FAS): This patient set includes all randomized patients who received at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Time to Death Over the Duration of the Trial | 28 Participants |
| Nerandomilast 9 mg BID | Time to Death Over the Duration of the Trial | 26 Participants |
| Nerandomilast 18 mg BID | Time to Death Over the Duration of the Trial | 21 Participants |
Comparison: Analysis was performed using a Cox proportional hazards regression model that included baseline use of antifibrotic therapy (antifibrotic group vs non-antifibrotic group), age, baseline forced vital capacity (FVC) percentage predicted, baseline diffusing capacity of the lungs for carbon monoxide (DLCO) percentage predicted (corrected for hemoglobin levels), and treatment group as covariates.p-value: 0.908495% CI: [0.6, 1.76]Regression, Cox
Comparison: Analysis was performed using a Cox proportional hazards regression model that included baseline use of antifibrotic therapy (antifibrotic group vs non-antifibrotic group), age, baseline forced vital capacity (FVC) percentage predicted, baseline diffusing capacity of the lungs for carbon monoxide (DLCO) percentage predicted (corrected for hemoglobin levels), and treatment group as covariates.p-value: 0.468295% CI: [0.46, 1.43]Regression, Cox
Secondary
Time to First Acute IPF Exacerbation or Death Over the Duration of the Trial
The time to first acute IPF exacerbation or death during the trial is reported as the number of participants who experienced either event. Acute IPF is defined as 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 of less than 1 month's duration. Computed tomography showing new bilateral ground-glass opacity and/or consolidation superimposed on a background pattern consistent with IPF. 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.
Time frame: From first administration of any trial drug (Nerandomilast or Placebo) up to 22.9 months.
Population: Full Analysis Set (FAS): This patient set includes all randomized patients who received at least one dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Time to First Acute IPF Exacerbation or Death Over the Duration of the Trial | Acute IPF exacerbation | 30 Participants |
| Placebo | Time to First Acute IPF Exacerbation or Death Over the Duration of the Trial | Death | 19 Participants |
| Nerandomilast 9 mg BID | Time to First Acute IPF Exacerbation or Death Over the Duration of the Trial | Acute IPF exacerbation | 31 Participants |
| Nerandomilast 9 mg BID | Time to First Acute IPF Exacerbation or Death Over the Duration of the Trial | Death | 20 Participants |
| Nerandomilast 18 mg BID | Time to First Acute IPF Exacerbation or Death Over the Duration of the Trial | Acute IPF exacerbation | 38 Participants |
| Nerandomilast 18 mg BID | Time to First Acute IPF Exacerbation or Death Over the Duration of the Trial | Death | 12 Participants |
Comparison: Analysis was performed using a Cox proportional hazards regression model that included baseline use of antifibrotic therapy (antifibrotic group vs non-antifibrotic group), age, baseline forced vital capacity (FVC) percentage predicted, baseline diffusing capacity of the lungs for carbon monoxide (DLCO) percentage predicted (corrected for hemoglobin levels), and treatment group as covariates.p-value: 0.558395% CI: [0.76, 1.67]Regression, Cox
Comparison: Analysis was performed using a Cox proportional hazards regression model that included baseline use of antifibrotic therapy (antifibrotic group vs non-antifibrotic group), age, baseline forced vital capacity (FVC) percentage predicted, baseline diffusing capacity of the lungs for carbon monoxide (DLCO) percentage predicted (corrected for hemoglobin levels), and treatment group as covariates.p-value: 0.589695% CI: [0.75, 1.65]Regression, Cox
Secondary
Time to Hospitalization for Respiratory Cause or Death Over the Duration of the Trial
Time to hospitalization 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. If more than one component occurred on the same day, the patient was counted under the first event according to the hierarchy: hospitalization for respiratory cause, followed by death.
Time frame: From first administration of any trial drug (Nerandomilast or Placebo) up to 22.9 months.
Population: Full Analysis Set (FAS): This patient set includes all randomized patients who received at least one dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Time to Hospitalization for Respiratory Cause or Death Over the Duration of the Trial | Hospitalization for respiratory cause | 59 Participants |
| Placebo | Time to Hospitalization for Respiratory Cause or Death Over the Duration of the Trial | Death | 14 Participants |
| Nerandomilast 9 mg BID | Time to Hospitalization for Respiratory Cause or Death Over the Duration of the Trial | Hospitalization for respiratory cause | 57 Participants |
| Nerandomilast 9 mg BID | Time to Hospitalization for Respiratory Cause or Death Over the Duration of the Trial | Death | 11 Participants |
| Nerandomilast 18 mg BID | Time to Hospitalization for Respiratory Cause or Death Over the Duration of the Trial | Hospitalization for respiratory cause | 68 Participants |
| Nerandomilast 18 mg BID | Time to Hospitalization for Respiratory Cause or Death Over the Duration of the Trial | Death | 7 Participants |
Comparison: Analysis was performed using a Cox proportional hazards regression model that included baseline use of antifibrotic therapy (antifibrotic group vs non-antifibrotic group), age, baseline forced vital capacity (FVC) percentage predicted, baseline diffusing capacity of the lungs for carbon monoxide (DLCO) percentage predicted (corrected for hemoglobin levels), and treatment group as covariates.p-value: 0.903895% CI: [0.7, 1.36]Regression, Cox
Comparison: Analysis was performed using a Cox proportional hazards regression model that included baseline use of antifibrotic therapy (antifibrotic group vs non-antifibrotic group), age, baseline forced vital capacity (FVC) percentage predicted, baseline diffusing capacity of the lungs for carbon monoxide (DLCO) percentage predicted (corrected for hemoglobin levels), and treatment group as covariates.p-value: 0.468795% CI: [0.82, 1.56]Regression, Cox