Lung Diseases, Interstitial
Conditions
Brief summary
The aim of the current study is to investigate the efficacy and safety of nintedanib over 52 weeks in patients with Progressive Fibrosing Interstitial Lung Disease (PF-ILD) defined as patients who present with features of diffuse fibrosing lung disease of \>10% extent on high-resolution computed tomography (HRCT) and whose lung function and respiratory symptoms or chest imaging have worsened despite treatment with unapproved medications used in clinical practice to treat ILD. There is currently no efficacious treatment available for PF-ILD. Based on its efficacy and safety in Idiopathic Pulmonary Fibrosis (IPF), it is anticipated that Nintedanib will be a new treatment option for patients with PF-ILD.
Interventions
DRUGNintedanib
DRUGPlacebo
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Written Informed Consent consistent with International Conference on Harmonisation Harmonised Tripartite Guideline for Good Clinical Practice (ICH-GCP) and local laws signed prior to entry into the study (and prior to any study procedure including shipment of High Resolution Computer Tomography (HRCT) to reviewer). * Male or female patients aged \>= 18 years at Visit 1. * Patients with physician diagnosed Interstitial Lung Disease (ILD) who fulfil at least one of the following criteria for Progressive Fibrosing Interstitial Lung Disease (PF-ILD) within 24 months of screening visit (Visit 1) despite treatment with unapproved medications used in clinical practice to treat ILD, as assessed by the investigator (refer to
Exclusion criteria
): * Clinically significant decline in Forced Vital Capacity (FVC) % pred based on a relative decline of \>=10% * Marginal decline in FVC % pred based on a relative decline of .\>=5-\<10% combined with worsening of respiratory symptoms * Marginal decline in FVC % pred based on a relative decline of \>=5-\<10% combined with increasing extent of fibrotic changes on chest imaging * Worsening of respiratory symptoms as well as increasing extent of fibrotic changes on chest imaging \[Note: Changes attributable to comorbidities e.g. infection, heart failure must be excluded. Unapproved medications used in the clinical practice to treat ILD include but are not limited to corticosteroid, azathioprine, mycophenolate mofetil (MMF), n-acetylcysteine (NAC), rituximab, cyclophosphamide, cyclosporine, tacrolimus\]. * Fibrosing lung disease on HRCT, defined as reticular abnormality with traction bronchiectasis with or without honeycombing, with disease extent of \>10%, performed within 12 months of Visit 1 as confirmed by central readers. * For patients with underlying Connective Tissue Disease (CTD): stable CTD as defined by no initiation of new therapy or withdrawal of therapy for CTD within 6 weeks prior to Visit 1. * Carbon Monoxide Diffusion Capacity (DLCO) corrected for Haemoglobin (Hb) \[visit 1\] ≥ 30% and \<80% predicted of normal at Visit 2 * FVC \>= 45% predicted at Visit 2
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Annual Rate of Decline in Forced Vital Capacity - Overall Population | Baseline, 2, 4, 6, 12, 24, 36, 52 weeks after first drug intake (planned post-baseline visits) | Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. Overall population consists of all randomized participants with HRCT fibrotic pattern=UIP-like fibrotic pattern only or HRCT fibrotic pattern= Other fibrotic patterns. Annual rate of decline in Forced Vital Capacity in milliliter (mL) per year in the overall population is based on a random coefficient regression with fixed effects for treatment, HRCT fibrotic pattern, and baseline FVC \[mL\], and including treatment-by-time and baseline-by-time interactions. Within-participant errors are modelled by an unstructured variance-covariance matrix. |
| Annual Rate of Decline in Forced Vital Capacity - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only | Baseline, 2, 4, 6, 12, 24, 36, 52 weeks after first drug intake (planned post-baseline visits) | Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. Annual rate of decline in Forced Vital Capacity in milliliter (mL) per year in participants with HRCT fibrotic pattern=UIP-like fibrotic pattern only is based on a random coefficient regression with fixed effects for treatment, baseline FVC \[mL\], and including treatment-by-time and baseline-by-time interactions. Within-participant errors are modelled by an unstructured variance-covariance matrix. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to First Acute Interstitial Lung Disease (ILD) Exacerbation or Death Over 52 Weeks - Overall Population | From first drug intake until date of first acute ILD exacerbation or date of death or last contact date, up to 372 days | Time to first acute ILD exacerbation or death over 52 weeks was defined as time to first acute ILD exacerbation or death due to any cause within the first 52 weeks and was computed as earliest of date of first documented acute ILD exacerbation or death - date of first drug intake + 1. Participants alive who did not experience any ILD exacerbation event or with unknown status within the first 52 weeks were censored. |
| Time to First Acute Interstitial Lung Disease (ILD) Exacerbation or Death Over 52 Weeks - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only | From first drug intake until date of first acute ILD exacerbation or date of death or last contact date, up to 372 days | Time to first acute ILD exacerbation or death over 52 weeks was defined as time to first acute ILD exacerbation or death due to any cause within the first 52 weeks and was computed as earliest of date of first documented acute ILD exacerbation or death - date of first drug intake + 1. Participants alive who did not experience any ILD exacerbation event or with unknown status within the first 52 weeks were censored. |
| Time to Death Over 52 Weeks - Overall Population | From first drug intake until date of death or last contact date, up to 372 days | Time to death over 52 weeks defined as the time from date of first drug intake until date of death from any cause for participants with known date of death (from any cause) within the first 52 weeks. Participants with no event (death from any cause) or unknown status within the first 52 weeks were censored. |
| Time to Death Over 52 Weeks - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only | From first drug intake until date of death or last contact date, up to 372 days | Time to death over 52 weeks defined as the time from date of first drug intake until date of death from any cause for participants with known date of death (from any cause) within the first 52 weeks. Participants with no event (death from any cause) or unknown status within the first 52 weeks were censored. |
| Time to Death Due to Respiratory Cause Over 52 Weeks - Overall Population | From date of first trial drug intake up to date of death from respiratory causes or last contact date, up to 372 days | Time to death due to respiratory cause over 52 weeks is defined as the time from date of first drug intake until date of death attributed to respiratory causes (determined by an independent Adjudication Committee) for participants with known date of death (from respiratory causes) within the first 52 weeks. Participants with no event (death from respiratory causes) or unknown status within the first 52 weeks were censored. As less than 4.95% of the total of participants in the analysis population experienced an event, only descriptive statistics were performed, as pre-specified. |
| Time to Death Due to Respiratory Cause Over 52 Weeks - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only | From date of first trial drug intake up to date of death from respiratory causes or last contact date, up to 372 days | Time to death due to respiratory cause over 52 weeks is defined as the time from date of first drug intake until date of death attributed to respiratory causes (determined by an independent Adjudication Committee) for participants with known date of death (from respiratory causes) within the first 52 weeks. Participants with no event (death from respiratory causes) or unknown status within the first 52 weeks were censored. As less than 4.95% of the total of participants in the analysis population experienced an event, only descriptive statistics were performed, as pre-specified. |
| Time to Progression or Death Over 52 Weeks - Overall Population | From first drug intake until date of progression or date of death or last contact date, up to 372 days | Time to progression or death over 52 weeks is defined as the time from date of first drug intake to date of progression, or date of death (from any cause) if a participant died earlier. Participants with no event (progression or death from any cause) or unknown status were censored. Date of progression is defined as the date when ≥ 10% of absolute decline in FVC percent predicted compared to baseline occured for the first time. Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. Predicted normal values of FVC were calculated according to the Global Lung Initiative. FVC percent predicted (FVC % pred) is the FVC divided by its predicted value in percent. |
| Time to Progression or Death Over 52 Weeks - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only | From first drug intake until date of progression or date of death or last contact date, up to 372 days | Time to progression or death over 52 weeks is defined as the time from date of first drug intake to date of progression, or date of death (from any cause) if a participant died earlier. Participants with no event (progression or death from any cause) or unknown status were censored. Date of progression is defined as the date when ≥ 10% of absolute decline in FVC percent predicted compared to baseline occured for the first time. Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. Predicted normal values of FVC were calculated according to the Global Lung Initiative. FVC percent predicted (FVC % pred) is the FVC divided by its predicted value in percent. |
| Absolute Change From Baseline in King's Brief Interstitial Lung Disease Questionnaire (K-BILD) Total Score at Week 52 - Overall Population | Baseline, 12, 24, 36, 52 weeks after first drug intake (planned post-baseline visits) | King's Brief Interstitial Lung Disease questionnaire (K-BILD) consists of 15 items and 3 domains: breathlessness and activities, psychological, and chest symptoms. Possible score ranges from 0-100, score of 100 representing the best health status. If missing items were \>50% per domain, the domain score was set to missing. If any of the domain scores were missing, the total score was set to missing. Absolute change from baseline in K-BILD Total score at week 52 in the overall population was based on a Mixed Model Repeated Measures (MMRM), with fixed effects for baseline K-BILD Total score, HRCT fibrotic pattern, visit, treatment-by-visit interaction, baseline-by-visit interactions and random effect for participant. Visit was the repeated measure. Within-participant errors were modelled by unstructured variance-covariance matrix. |
| Percentage of Participants With a Relative Decline From Baseline in FVC Percent Predicted of More Than 10 Percent at Week 52 - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only | Baseline and up to 52 weeks after first drug intake | Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. Predicted normal values of FVC were calculated according to the Global Lung Initiative. FVC percent predicted (FVC % pred) is the FVC divided by its predicted value in percent. Participants with relative decline from baseline in FVC % pred greater than 10% at week 52 were those participants with a negative relative change from baseline in FVC % pred at week 52 the absolute value of which being greater than 10% and those participants with missing data (worst case analysis). |
| Percentage of Participants With a Relative Decline From Baseline in FVC Percent Predicted of More Than 5 Percent at Week 52 - Overall Population | Baseline and up to 52 weeks after first drug intake | Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. Predicted normal values of FVC were calculated according to the Global Lung Initiative. FVC percent predicted (FVC % pred) is the FVC divided by its predicted value in percent. Participants with relative decline from baseline in FVC % pred greater than 5% at week 52 were those participants with a negative relative change from baseline in FVC % pred at week 52 the absolute value of which being greater than 5% and those participants with missing data (worst case analysis). |
| Percentage of Participants With a Relative Decline From Baseline in FVC Percent Predicted of More Than 5 Percent at Week 52 - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only | Baseline and up to 52 weeks after first drug intake | Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. Predicted normal values of FVC were calculated according to the Global Lung Initiative. FVC percent predicted (FVC % pred) is the FVC divided by its predicted value in percent. Participants with relative decline from baseline in FVC % pred greater than 5% at week 52 were those participants with a negative relative change from baseline in FVC % pred at week 52 the absolute value of which being greater than 5% and those participants with missing data (worst case analysis). |
| Absolute Change From Baseline in Living With Pulmonary Fibrosis (L-PF) Symptoms Dyspnea Domain Score at Week 52 - Overall Population | Baseline, 12, 24, 36, 52 weeks after first drug intake (planned post-baseline visits) | Living with Pulmonary Fibrosis (L-PF) questionnaire is a 44 item questionnaire with two modules Symptoms (23 items) and Impacts (21 items) where the symptoms module yields three domain scores dyspnea, cough and fatigue as well as a total symptoms score (impacts module yields a single impacts score). L-PF Symptoms dyspnea domain score (dyspnea score) ranges from 0-100, the higher the score the greater the impairment. If missing items were ≥50 % within a score, then the corresponding score was set to missing. Absolute change from baseline in dyspnea score at week 52 is based on a Mixed Model Repeated Measures, with fixed effects for baseline dyspnea score, HRCT fibrotic pattern, visit, treatment-by-visit interaction, baseline dyspnea score-by-visit interaction and random effect for participant, visit as repeated measure. The Adjusted mean is based on all analysed participants in the model (not only participants with a baseline and measurement at week 52). |
| Absolute Change From Baseline in L-PF Symptoms Dyspnea Domain Score at Week 52 - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only | Baseline, 12, 24, 36, 52 weeks after first drug intake (planned post-baseline visits) | Living with Pulmonary Fibrosis (L-PF) questionnaire is a 44 item questionnaire with two modules Symptoms (23 items) and Impacts (21 items) where the symptoms module yields three domain scores dyspnea, cough and fatigue as well as a total symptoms score (impacts module yields a single impacts score). L-PF Symptoms dyspnea domain score (dyspnea score) ranges from 0-100, the higher the score the greater the impairment. If missing items were ≥50 % within a score, then the corresponding score was set to missing. Absolute change from baseline in dyspnea score at week 52 is based on a Mixed Model Repeated Measures, with fixed effects for baseline dyspnea score, visit, treatment-by-visit interaction, baseline dyspnea score-by-visit interaction and random effect for participant, visit as repeated measure. The Adjusted mean is based on all analysed participants in the model (not only participants with a baseline and measurement at week 52). |
| Absolute Change From Baseline in L-PF Symptoms Cough Domain Score at Week 52 - Overall Population | Baseline, 12, 24, 36, 52 weeks after first drug intake (planned post-baseline visits) | Living with Pulmonary Fibrosis (L-PF) questionnaire is a 44 item questionnaire with two modules Symptoms (23 items) and Impacts (21 items) where the symptoms module yields three domain scores dyspnea, cough and fatigue as well as a total symptoms score (impacts module yields a single impacts score). L-PF Symptoms cough domain score (cough score) ranges from 0-100, the higher the score the greater the impairment. If missing items were ≥50 % within a score, then the corresponding score was set to missing. Absolute change from baseline in cough score at week 52 is based on a Mixed Model Repeated Measures, with fixed effects for baseline cough score, HRCT fibrotic pattern, visit, treatment-by-visit interaction, baseline cough score-by-visit interaction and random effect for participant, visit as repeated measure. The Adjusted mean is based on all analysed participants in the model (not only participants with a baseline and measurement at week 52). |
| Absolute Change From Baseline in Living With Pulmonary Fibrosis (L-PF) Symptoms Cough Domain Score at Week 52 - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only | Baseline, 12, 24, 36, 52 weeks after first drug intake (planned post-baseline visits) | Living with Pulmonary Fibrosis (L-PF) questionnaire is a 44 item questionnaire with two modules Symptoms (23 items) and Impacts (21 items) where the symptoms module yields three domain scores dyspnea, cough and fatigue as well as a total symptoms score (impacts module yields a single impacts score). L-PF Symptoms cough domain score (cough score) ranges from 0-100, the higher the score the greater the impairment. If missing items were ≥50 % within a score, then the corresponding score was set to missing. Absolute change from baseline in cough score at week 52 is based on a Mixed Model Repeated Measures, with fixed effects for baseline cough score, visit, treatment-by-visit interaction, baseline cough score-by-visit interaction and random effect for participant, visit as repeated measure. The Adjusted mean is based on all analysed participants in the model (not only participants with a baseline and measurement at week 52). |
| Percentage of Participants With a Relative Decline From Baseline in FVC Percent Predicted of More Than 10 Percent at Week 52 - Overall Population | Baseline and up to 52 weeks after first drug intake | Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. Predicted normal values of FVC were calculated according to the Global Lung Initiative. FVC percent predicted (FVC % pred) is the FVC divided by its predicted value in percent. Participants with relative decline from baseline in FVC % pred greater than 10% at week 52 were those participants with a negative relative change from baseline in FVC % pred at week 52 the absolute value of which being greater than 10% and those participants with missing data (worst case analysis). |
| Absolute Change From Baseline in King's Brief Interstitial Lung Disease (K-BILD) Questionnaire Total Score at Week 52 - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only | Baseline, 12, 24, 36, 52 weeks after first drug intake (planned post-baseline visits) | King's Brief Interstitial Lung Disease questionnaire (K-BILD) consists of 15 items and 3 domains: breathlessness and activities, psychological, and chest symptoms. Possible score ranges from 0-100, score of 100 representing the best health status. If missing items were \>50% per domain, the domain score was set to missing. If any of the domain scores were missing, the total score was set to missing. Absolute change from baseline in K-BILD Total score at week 52 in participants with HRCT fibrotic pattern=UIP-like fibrotic pattern only was based on a Mixed Model Repeated Measures (MMRM), with fixed effects for baseline K-BILD Total score, HRCT fibrotic pattern, visit, treatment-by-visit interaction, baseline-by-visit interactions and random effect for participant. Visit was the repeated measure. Within-participant errors were modelled by unstructured variance-covariance matrix. |
Countries
Argentina, Belgium, Canada, Chile, China, France, Germany, Italy, Japan, Poland, Russia, South Korea, Spain, United Kingdom, United States
Participant flow
Recruitment details
Randomized (1:1 ratio), placebo-controlled, double-blind, parallel-group trial comparing nintedanib to placebo over a 52-week treatment period (Part A). Participants continued on blinded, randomized treatment beyond 52 weeks (Part B). Data base lock (DBL) one was on 6-June-2019, DBL two was on 11-September-2019. Overall Study Period=Part A and B.
Pre-assignment details
All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.
Participants by arm
| Arm | Count |
|---|---|
| 150 mg Nintedanib 150 milligram (mg) Nintedanib as soft gelatine capsule, administered orally, twice daily (bid), with optional dose reduction to 100 mg bid to manage adverse events (AEs). Continuous daily dosing over a 52-week treatment period (Part A). After completion of the 52-week treatment period, participants continued on blinded treatment until the end of the trial or until a reason for treatment withdrawal was met (Part B). | 332 |
| Placebo 150 mg Nintedanib matching placebo, soft gelatine capsule, administered orally, bid, with optional dose reduction to 100 mg bid to manage AEs. Continuous daily dosing over a 52-week treatment period (Part A). After completion of the 52-week treatment period, participants continued on blinded treatment until the end of the trial or until a reason for treatment withdrawal was met (Part B). | 331 |
| Total | 663 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 85 | 62 |
| Overall Study | Lost to Follow-up | 0 | 2 |
| Overall Study | Other reason not defined above | 7 | 13 |
| Overall Study | Protocol Violation | 1 | 2 |
| Overall Study | Withdrawal by Subject | 21 | 21 |
Baseline characteristics
| Characteristic | Total | Placebo | 150 mg Nintedanib |
|---|---|---|---|
| Age, Continuous | 65.8 Years STANDARD_DEVIATION 9.8 | 66.3 Years STANDARD_DEVIATION 9.8 | 65.2 Years STANDARD_DEVIATION 9.7 |
| Baseline Forced Vital Capacity (FVC) - Overall Population | 2330.62 Milliliter (mL) STANDARD_DEVIATION 733.62 | 2321.15 Milliliter (mL) STANDARD_DEVIATION 727.97 | 2340.07 Milliliter (mL) STANDARD_DEVIATION 740.19 |
| Baseline FVC - Participants with HRCT fibrotic pattern=UIP-like fibrotic pattern only | 2368.51 Milliliter (mL) STANDARD_DEVIATION 740.89 | 2373.59 Milliliter (mL) STANDARD_DEVIATION 720.05 | 2363.43 Milliliter (mL) STANDARD_DEVIATION 762.89 |
| Baseline High Resolution Computed Tomography (HRCT) fibrotic pattern Other fibrotic patterns | 251 Participants | 125 Participants | 126 Participants |
| Baseline High Resolution Computed Tomography (HRCT) fibrotic pattern UIP-like fibrotic pattern only | 412 Participants | 206 Participants | 206 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 96 Participants | 49 Participants | 47 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 567 Participants | 282 Participants | 285 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 163 Participants | 80 Participants | 83 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants | 5 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 488 Participants | 246 Participants | 242 Participants |
| Sex: Female, Male Female | 307 Participants | 154 Participants | 153 Participants |
| Sex: Female, Male Male | 356 Participants | 177 Participants | 179 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 36 / 332 | 45 / 331 |
| other Total, other adverse events | 308 / 332 | 266 / 331 |
| serious Total, serious adverse events | 147 / 332 | 164 / 331 |
Outcome results
Primary
Annual Rate of Decline in Forced Vital Capacity - Overall Population
Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. Overall population consists of all randomized participants with HRCT fibrotic pattern=UIP-like fibrotic pattern only or HRCT fibrotic pattern= Other fibrotic patterns. Annual rate of decline in Forced Vital Capacity in milliliter (mL) per year in the overall population is based on a random coefficient regression with fixed effects for treatment, HRCT fibrotic pattern, and baseline FVC \[mL\], and including treatment-by-time and baseline-by-time interactions. Within-participant errors are modelled by an unstructured variance-covariance matrix.
Time frame: Baseline, 2, 4, 6, 12, 24, 36, 52 weeks after first drug intake (planned post-baseline visits)
Population: All randomized participants in the overall population who received at least 1 dose of trial medication.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| 150 mg Nintedanib | Annual Rate of Decline in Forced Vital Capacity - Overall Population | -80.82 Milliliter per year |
| Placebo | Annual Rate of Decline in Forced Vital Capacity - Overall Population | -187.78 Milliliter per year |
Comparison: The decrease in FVC was assumed to be linear within each participant over 52 weeks. The intercepts and slopes were assumed to be normally distributed with unstructured covariance matrix. The within participant error was assumed to be independent and normally distributed with mean 0 and a common variance. The Kenward-Roger approximation was used to estimate denominator degrees of freedom and adjust standard errors (SEs).p-value: <0.000195% CI: [65.42, 148.5]Mixed Models Analysis
Primary
Annual Rate of Decline in Forced Vital Capacity - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only
Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. Annual rate of decline in Forced Vital Capacity in milliliter (mL) per year in participants with HRCT fibrotic pattern=UIP-like fibrotic pattern only is based on a random coefficient regression with fixed effects for treatment, baseline FVC \[mL\], and including treatment-by-time and baseline-by-time interactions. Within-participant errors are modelled by an unstructured variance-covariance matrix.
Time frame: Baseline, 2, 4, 6, 12, 24, 36, 52 weeks after first drug intake (planned post-baseline visits)
Population: All randomized participants with HRCT fibrotic pattern=UIP-like fibrotic pattern only who received at least 1 dose of trial medication.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| 150 mg Nintedanib | Annual Rate of Decline in Forced Vital Capacity - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only | -82.87 Milliliter per year |
| Placebo | Annual Rate of Decline in Forced Vital Capacity - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only | -211.07 Milliliter per year |
Comparison: The decrease in FVC was assumed to be linear within each participant over 52 weeks. The intercepts and slopes were assumed to be normally distributed with unstructured covariance matrix. The within participant error was assumed to be independent and normally distributed with mean 0 and a common variance. The Kenward-Roger approximation was used to estimate denominator degrees of freedom and adjust standard errors (SEs).p-value: <0.000195% CI: [70.81, 185.59]Mixed Models Analysis
Secondary
Absolute Change From Baseline in King's Brief Interstitial Lung Disease (K-BILD) Questionnaire Total Score at Week 52 - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only
King's Brief Interstitial Lung Disease questionnaire (K-BILD) consists of 15 items and 3 domains: breathlessness and activities, psychological, and chest symptoms. Possible score ranges from 0-100, score of 100 representing the best health status. If missing items were \>50% per domain, the domain score was set to missing. If any of the domain scores were missing, the total score was set to missing. Absolute change from baseline in K-BILD Total score at week 52 in participants with HRCT fibrotic pattern=UIP-like fibrotic pattern only was based on a Mixed Model Repeated Measures (MMRM), with fixed effects for baseline K-BILD Total score, HRCT fibrotic pattern, visit, treatment-by-visit interaction, baseline-by-visit interactions and random effect for participant. Visit was the repeated measure. Within-participant errors were modelled by unstructured variance-covariance matrix.
Time frame: Baseline, 12, 24, 36, 52 weeks after first drug intake (planned post-baseline visits)
Population: All randomized participants with HRCT fibrotic pattern=UIP-like fibrotic pattern only who received at least 1 dose of trial medication and who contributed to the model evaluation.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| 150 mg Nintedanib | Absolute Change From Baseline in King's Brief Interstitial Lung Disease (K-BILD) Questionnaire Total Score at Week 52 - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only | 0.75 Unit on scale |
| Placebo | Absolute Change From Baseline in King's Brief Interstitial Lung Disease (K-BILD) Questionnaire Total Score at Week 52 - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only | -0.78 Unit on scale |
p-value: 0.174795% CI: [-0.68, 3.74]Mixed Model Repeated Measures (MMRM)
Secondary
Absolute Change From Baseline in King's Brief Interstitial Lung Disease Questionnaire (K-BILD) Total Score at Week 52 - Overall Population
King's Brief Interstitial Lung Disease questionnaire (K-BILD) consists of 15 items and 3 domains: breathlessness and activities, psychological, and chest symptoms. Possible score ranges from 0-100, score of 100 representing the best health status. If missing items were \>50% per domain, the domain score was set to missing. If any of the domain scores were missing, the total score was set to missing. Absolute change from baseline in K-BILD Total score at week 52 in the overall population was based on a Mixed Model Repeated Measures (MMRM), with fixed effects for baseline K-BILD Total score, HRCT fibrotic pattern, visit, treatment-by-visit interaction, baseline-by-visit interactions and random effect for participant. Visit was the repeated measure. Within-participant errors were modelled by unstructured variance-covariance matrix.
Time frame: Baseline, 12, 24, 36, 52 weeks after first drug intake (planned post-baseline visits)
Population: All randomized participants in the overall population who received at least 1 dose of trial medication and contributed to the model evaluation.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| 150 mg Nintedanib | Absolute Change From Baseline in King's Brief Interstitial Lung Disease Questionnaire (K-BILD) Total Score at Week 52 - Overall Population | 0.55 Unit on scale |
| Placebo | Absolute Change From Baseline in King's Brief Interstitial Lung Disease Questionnaire (K-BILD) Total Score at Week 52 - Overall Population | -0.79 Unit on scale |
p-value: 0.111595% CI: [-0.31, 2.98]Mixed Model Repeated Measures (MMRM)
Secondary
Absolute Change From Baseline in Living With Pulmonary Fibrosis (L-PF) Symptoms Cough Domain Score at Week 52 - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only
Living with Pulmonary Fibrosis (L-PF) questionnaire is a 44 item questionnaire with two modules Symptoms (23 items) and Impacts (21 items) where the symptoms module yields three domain scores dyspnea, cough and fatigue as well as a total symptoms score (impacts module yields a single impacts score). L-PF Symptoms cough domain score (cough score) ranges from 0-100, the higher the score the greater the impairment. If missing items were ≥50 % within a score, then the corresponding score was set to missing. Absolute change from baseline in cough score at week 52 is based on a Mixed Model Repeated Measures, with fixed effects for baseline cough score, visit, treatment-by-visit interaction, baseline cough score-by-visit interaction and random effect for participant, visit as repeated measure. The Adjusted mean is based on all analysed participants in the model (not only participants with a baseline and measurement at week 52).
Time frame: Baseline, 12, 24, 36, 52 weeks after first drug intake (planned post-baseline visits)
Population: All randomized participants with HRCT fibrotic pattern=UIP-like fibrotic pattern only who received at least 1 dose of trial medication and contributed to the model evaluation.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| 150 mg Nintedanib | Absolute Change From Baseline in Living With Pulmonary Fibrosis (L-PF) Symptoms Cough Domain Score at Week 52 - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only | -3.20 Unit on scale |
| Placebo | Absolute Change From Baseline in Living With Pulmonary Fibrosis (L-PF) Symptoms Cough Domain Score at Week 52 - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only | 4.09 Unit on scale |
95% CI: [-11.86, -2.71]Mixed Model Repeated Measures
Secondary
Absolute Change From Baseline in Living With Pulmonary Fibrosis (L-PF) Symptoms Dyspnea Domain Score at Week 52 - Overall Population
Living with Pulmonary Fibrosis (L-PF) questionnaire is a 44 item questionnaire with two modules Symptoms (23 items) and Impacts (21 items) where the symptoms module yields three domain scores dyspnea, cough and fatigue as well as a total symptoms score (impacts module yields a single impacts score). L-PF Symptoms dyspnea domain score (dyspnea score) ranges from 0-100, the higher the score the greater the impairment. If missing items were ≥50 % within a score, then the corresponding score was set to missing. Absolute change from baseline in dyspnea score at week 52 is based on a Mixed Model Repeated Measures, with fixed effects for baseline dyspnea score, HRCT fibrotic pattern, visit, treatment-by-visit interaction, baseline dyspnea score-by-visit interaction and random effect for participant, visit as repeated measure. The Adjusted mean is based on all analysed participants in the model (not only participants with a baseline and measurement at week 52).
Time frame: Baseline, 12, 24, 36, 52 weeks after first drug intake (planned post-baseline visits)
Population: All randomized participants in the overall population who received at least 1 dose of trial medication and contributed to the model evaluation.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| 150 mg Nintedanib | Absolute Change From Baseline in Living With Pulmonary Fibrosis (L-PF) Symptoms Dyspnea Domain Score at Week 52 - Overall Population | 4.28 Unit on scale |
| Placebo | Absolute Change From Baseline in Living With Pulmonary Fibrosis (L-PF) Symptoms Dyspnea Domain Score at Week 52 - Overall Population | 7.81 Unit on scale |
95% CI: [-6.14, -0.92]Mixed Model Repeated Measures
Secondary
Absolute Change From Baseline in L-PF Symptoms Cough Domain Score at Week 52 - Overall Population
Living with Pulmonary Fibrosis (L-PF) questionnaire is a 44 item questionnaire with two modules Symptoms (23 items) and Impacts (21 items) where the symptoms module yields three domain scores dyspnea, cough and fatigue as well as a total symptoms score (impacts module yields a single impacts score). L-PF Symptoms cough domain score (cough score) ranges from 0-100, the higher the score the greater the impairment. If missing items were ≥50 % within a score, then the corresponding score was set to missing. Absolute change from baseline in cough score at week 52 is based on a Mixed Model Repeated Measures, with fixed effects for baseline cough score, HRCT fibrotic pattern, visit, treatment-by-visit interaction, baseline cough score-by-visit interaction and random effect for participant, visit as repeated measure. The Adjusted mean is based on all analysed participants in the model (not only participants with a baseline and measurement at week 52).
Time frame: Baseline, 12, 24, 36, 52 weeks after first drug intake (planned post-baseline visits)
Population: All randomized participants in the overall population who received at least 1 dose of trial medication and contributed to the model evaluation.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| 150 mg Nintedanib | Absolute Change From Baseline in L-PF Symptoms Cough Domain Score at Week 52 - Overall Population | -1.84 Unit on scale |
| Placebo | Absolute Change From Baseline in L-PF Symptoms Cough Domain Score at Week 52 - Overall Population | 4.25 Unit on scale |
95% CI: [-9.65, -2.53]Mixed Model Repeated Measures
Secondary
Absolute Change From Baseline in L-PF Symptoms Dyspnea Domain Score at Week 52 - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only
Living with Pulmonary Fibrosis (L-PF) questionnaire is a 44 item questionnaire with two modules Symptoms (23 items) and Impacts (21 items) where the symptoms module yields three domain scores dyspnea, cough and fatigue as well as a total symptoms score (impacts module yields a single impacts score). L-PF Symptoms dyspnea domain score (dyspnea score) ranges from 0-100, the higher the score the greater the impairment. If missing items were ≥50 % within a score, then the corresponding score was set to missing. Absolute change from baseline in dyspnea score at week 52 is based on a Mixed Model Repeated Measures, with fixed effects for baseline dyspnea score, visit, treatment-by-visit interaction, baseline dyspnea score-by-visit interaction and random effect for participant, visit as repeated measure. The Adjusted mean is based on all analysed participants in the model (not only participants with a baseline and measurement at week 52).
Time frame: Baseline, 12, 24, 36, 52 weeks after first drug intake (planned post-baseline visits)
Population: All randomized participants with HRCT fibrotic pattern=UIP-like fibrotic pattern only who received at least 1 dose of trial medication and contributed to the model evaluation.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| 150 mg Nintedanib | Absolute Change From Baseline in L-PF Symptoms Dyspnea Domain Score at Week 52 - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only | 4.14 Unit on scale |
| Placebo | Absolute Change From Baseline in L-PF Symptoms Dyspnea Domain Score at Week 52 - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only | 8.32 Unit on scale |
95% CI: [-7.48, -0.88]Mixed Model Repeated Measures
Secondary
Percentage of Participants With a Relative Decline From Baseline in FVC Percent Predicted of More Than 10 Percent at Week 52 - Overall Population
Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. Predicted normal values of FVC were calculated according to the Global Lung Initiative. FVC percent predicted (FVC % pred) is the FVC divided by its predicted value in percent. Participants with relative decline from baseline in FVC % pred greater than 10% at week 52 were those participants with a negative relative change from baseline in FVC % pred at week 52 the absolute value of which being greater than 10% and those participants with missing data (worst case analysis).
Time frame: Baseline and up to 52 weeks after first drug intake
Population: All randomized participants in the overall population who received at least 1 dose of trial medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 150 mg Nintedanib | Percentage of Participants With a Relative Decline From Baseline in FVC Percent Predicted of More Than 10 Percent at Week 52 - Overall Population | 40.7 Percentage of participants |
| Placebo | Percentage of Participants With a Relative Decline From Baseline in FVC Percent Predicted of More Than 10 Percent at Week 52 - Overall Population | 48.9 Percentage of participants |
95% CI: [0.52, 0.96]Regression, Logistic
Secondary
Percentage of Participants With a Relative Decline From Baseline in FVC Percent Predicted of More Than 10 Percent at Week 52 - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only
Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. Predicted normal values of FVC were calculated according to the Global Lung Initiative. FVC percent predicted (FVC % pred) is the FVC divided by its predicted value in percent. Participants with relative decline from baseline in FVC % pred greater than 10% at week 52 were those participants with a negative relative change from baseline in FVC % pred at week 52 the absolute value of which being greater than 10% and those participants with missing data (worst case analysis).
Time frame: Baseline and up to 52 weeks after first drug intake
Population: All randomized participants with HRCT fibrotic pattern=UIP-like fibrotic pattern only who received at least 1 dose of trial medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 150 mg Nintedanib | Percentage of Participants With a Relative Decline From Baseline in FVC Percent Predicted of More Than 10 Percent at Week 52 - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only | 41.3 Percentage of participants |
| Placebo | Percentage of Participants With a Relative Decline From Baseline in FVC Percent Predicted of More Than 10 Percent at Week 52 - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only | 52.4 Percentage of participants |
95% CI: [0.43, 0.94]Regression, Logistic
Secondary
Percentage of Participants With a Relative Decline From Baseline in FVC Percent Predicted of More Than 5 Percent at Week 52 - Overall Population
Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. Predicted normal values of FVC were calculated according to the Global Lung Initiative. FVC percent predicted (FVC % pred) is the FVC divided by its predicted value in percent. Participants with relative decline from baseline in FVC % pred greater than 5% at week 52 were those participants with a negative relative change from baseline in FVC % pred at week 52 the absolute value of which being greater than 5% and those participants with missing data (worst case analysis).
Time frame: Baseline and up to 52 weeks after first drug intake
Population: All randomized participants in the overall population who received at least 1 dose of trial medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 150 mg Nintedanib | Percentage of Participants With a Relative Decline From Baseline in FVC Percent Predicted of More Than 5 Percent at Week 52 - Overall Population | 52.4 Percentage of participants |
| Placebo | Percentage of Participants With a Relative Decline From Baseline in FVC Percent Predicted of More Than 5 Percent at Week 52 - Overall Population | 68.6 Percentage of participants |
95% CI: [0.36, 0.68]Regression, Logistic
Secondary
Percentage of Participants With a Relative Decline From Baseline in FVC Percent Predicted of More Than 5 Percent at Week 52 - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only
Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. Predicted normal values of FVC were calculated according to the Global Lung Initiative. FVC percent predicted (FVC % pred) is the FVC divided by its predicted value in percent. Participants with relative decline from baseline in FVC % pred greater than 5% at week 52 were those participants with a negative relative change from baseline in FVC % pred at week 52 the absolute value of which being greater than 5% and those participants with missing data (worst case analysis).
Time frame: Baseline and up to 52 weeks after first drug intake
Population: All randomized participants with HRCT fibrotic pattern=UIP-like fibrotic pattern only who received at least 1 dose of trial medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 150 mg Nintedanib | Percentage of Participants With a Relative Decline From Baseline in FVC Percent Predicted of More Than 5 Percent at Week 52 - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only | 52.4 Percentage of participants |
| Placebo | Percentage of Participants With a Relative Decline From Baseline in FVC Percent Predicted of More Than 5 Percent at Week 52 - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only | 70.4 Percentage of participants |
95% CI: [0.31, 0.69]Regression, Logistic
Secondary
Time to Death Due to Respiratory Cause Over 52 Weeks - Overall Population
Time to death due to respiratory cause over 52 weeks is defined as the time from date of first drug intake until date of death attributed to respiratory causes (determined by an independent Adjudication Committee) for participants with known date of death (from respiratory causes) within the first 52 weeks. Participants with no event (death from respiratory causes) or unknown status within the first 52 weeks were censored. As less than 4.95% of the total of participants in the analysis population experienced an event, only descriptive statistics were performed, as pre-specified.
Time frame: From date of first trial drug intake up to date of death from respiratory causes or last contact date, up to 372 days
Population: All randomized participants in the overall population who received at least 1 dose of trial medication.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 150 mg Nintedanib | Time to Death Due to Respiratory Cause Over 52 Weeks - Overall Population | NA Days |
| Placebo | Time to Death Due to Respiratory Cause Over 52 Weeks - Overall Population | NA Days |
Secondary
Time to Death Due to Respiratory Cause Over 52 Weeks - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only
Time to death due to respiratory cause over 52 weeks is defined as the time from date of first drug intake until date of death attributed to respiratory causes (determined by an independent Adjudication Committee) for participants with known date of death (from respiratory causes) within the first 52 weeks. Participants with no event (death from respiratory causes) or unknown status within the first 52 weeks were censored. As less than 4.95% of the total of participants in the analysis population experienced an event, only descriptive statistics were performed, as pre-specified.
Time frame: From date of first trial drug intake up to date of death from respiratory causes or last contact date, up to 372 days
Population: All randomized participants with HRCT fibrotic pattern=UIP-like fibrotic pattern only who received at least 1 dose of trial medication.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 150 mg Nintedanib | Time to Death Due to Respiratory Cause Over 52 Weeks - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only | NA Days |
| Placebo | Time to Death Due to Respiratory Cause Over 52 Weeks - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only | NA Days |
Secondary
Time to Death Over 52 Weeks - Overall Population
Time to death over 52 weeks defined as the time from date of first drug intake until date of death from any cause for participants with known date of death (from any cause) within the first 52 weeks. Participants with no event (death from any cause) or unknown status within the first 52 weeks were censored.
Time frame: From first drug intake until date of death or last contact date, up to 372 days
Population: All randomized participants in the overall population who received at least 1 dose of trial medication.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 150 mg Nintedanib | Time to Death Over 52 Weeks - Overall Population | NA Days |
| Placebo | Time to Death Over 52 Weeks - Overall Population | NA Days |
p-value: 0.854495% CI: [0.47, 1.86]Log Rank
Secondary
Time to Death Over 52 Weeks - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only
Time to death over 52 weeks defined as the time from date of first drug intake until date of death from any cause for participants with known date of death (from any cause) within the first 52 weeks. Participants with no event (death from any cause) or unknown status within the first 52 weeks were censored.
Time frame: From first drug intake until date of death or last contact date, up to 372 days
Population: All randomized participants with HRCT fibrotic pattern=UIP-like fibrotic pattern only who received at least 1 dose of trial medication.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 150 mg Nintedanib | Time to Death Over 52 Weeks - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only | NA Days |
| Placebo | Time to Death Over 52 Weeks - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only | NA Days |
p-value: 0.329195% CI: [0.32, 1.47]Log Rank
Secondary
Time to First Acute Interstitial Lung Disease (ILD) Exacerbation or Death Over 52 Weeks - Overall Population
Time to first acute ILD exacerbation or death over 52 weeks was defined as time to first acute ILD exacerbation or death due to any cause within the first 52 weeks and was computed as earliest of date of first documented acute ILD exacerbation or death - date of first drug intake + 1. Participants alive who did not experience any ILD exacerbation event or with unknown status within the first 52 weeks were censored.
Time frame: From first drug intake until date of first acute ILD exacerbation or date of death or last contact date, up to 372 days
Population: All randomized participants in the overall population who received at least 1 dose of trial medication.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 150 mg Nintedanib | Time to First Acute Interstitial Lung Disease (ILD) Exacerbation or Death Over 52 Weeks - Overall Population | NA Days |
| Placebo | Time to First Acute Interstitial Lung Disease (ILD) Exacerbation or Death Over 52 Weeks - Overall Population | NA Days |
p-value: 0.394895% CI: [0.48, 1.34]Log Rank
Secondary
Time to First Acute Interstitial Lung Disease (ILD) Exacerbation or Death Over 52 Weeks - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only
Time to first acute ILD exacerbation or death over 52 weeks was defined as time to first acute ILD exacerbation or death due to any cause within the first 52 weeks and was computed as earliest of date of first documented acute ILD exacerbation or death - date of first drug intake + 1. Participants alive who did not experience any ILD exacerbation event or with unknown status within the first 52 weeks were censored.
Time frame: From first drug intake until date of first acute ILD exacerbation or date of death or last contact date, up to 372 days
Population: All randomized participants with HRCT fibrotic pattern=UIP-like fibrotic pattern only who received at least 1 dose of trial medication.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 150 mg Nintedanib | Time to First Acute Interstitial Lung Disease (ILD) Exacerbation or Death Over 52 Weeks - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only | NA Days |
| Placebo | Time to First Acute Interstitial Lung Disease (ILD) Exacerbation or Death Over 52 Weeks - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only | NA Days |
p-value: 0.198595% CI: [0.36, 1.24]Log Rank
Secondary
Time to Progression or Death Over 52 Weeks - Overall Population
Time to progression or death over 52 weeks is defined as the time from date of first drug intake to date of progression, or date of death (from any cause) if a participant died earlier. Participants with no event (progression or death from any cause) or unknown status were censored. Date of progression is defined as the date when ≥ 10% of absolute decline in FVC percent predicted compared to baseline occured for the first time. Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. Predicted normal values of FVC were calculated according to the Global Lung Initiative. FVC percent predicted (FVC % pred) is the FVC divided by its predicted value in percent.
Time frame: From first drug intake until date of progression or date of death or last contact date, up to 372 days
Population: All randomized participants in the overall population who received at least 1 dose of trial medication.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 150 mg Nintedanib | Time to Progression or Death Over 52 Weeks - Overall Population | NA Days |
| Placebo | Time to Progression or Death Over 52 Weeks - Overall Population | NA Days |
p-value: 0.001795% CI: [0.49, 0.85]Log Rank
Secondary
Time to Progression or Death Over 52 Weeks - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only
Time to progression or death over 52 weeks is defined as the time from date of first drug intake to date of progression, or date of death (from any cause) if a participant died earlier. Participants with no event (progression or death from any cause) or unknown status were censored. Date of progression is defined as the date when ≥ 10% of absolute decline in FVC percent predicted compared to baseline occured for the first time. Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. Predicted normal values of FVC were calculated according to the Global Lung Initiative. FVC percent predicted (FVC % pred) is the FVC divided by its predicted value in percent.
Time frame: From first drug intake until date of progression or date of death or last contact date, up to 372 days
Population: All randomized participants with HRCT fibrotic pattern=UIP-like fibrotic pattern only who received at least 1 dose of trial medication.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 150 mg Nintedanib | Time to Progression or Death Over 52 Weeks - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only | NA Days |
| Placebo | Time to Progression or Death Over 52 Weeks - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only | NA Days |
p-value: 0.008195% CI: [0.45, 0.89]Log Rank