Pulmonary Fibrosis
Conditions
Brief summary
Idiopathic Pulmonary Fibrosis (IPF) is a chronic disease of unknown cause that results in scarring of the lung and there is a high unmet medical need for effective treatment to halt lung function decline, delay or avoid exacerbation (flare-ups), and ultimately to reduce the death rate. In a large Phase 2 trial (1199.30) (NCT00514683), investigating the effects of 52 weeks of treatment with BIBF 1120 in patients with IPF, a positive effect was seen on lung function of patients treated with high dose of BIBF 1120 compared to placebo. Hence it is the purpose of this trial to investigate and confirm the efficacy and safety of BIBF 1120 at a high dose in treating patients with IPF, compared with placebo. The trial will be conducted as a prospective, randomised design with the aim to collect safety and efficacy data. Respiratory function is globally accepted for assessment of treatment effects in IPF patients. The chosen endpoint (Forced Vital Capacity (FVC) decline) is easy to obtain and is part of the usual examinations done in IPF patients.
Interventions
DRUGplacebo
placebo matching BIBF 1120 BID
DRUGBIBF 1120
BIBF 1120 BID (twice daily)
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age \>= 40 years; 2. IPF diagnosed, according to most recent American Thoracic Society (ATS), European Respiratory Society (ERS), Japanese Respiratory Society (JRS), Latin American Thoracic Association (ALAT) IPF guideline for diagnosis and management, within 5 years; 3. Combination of High Resolution Computerized Tomography (HRCT) pattern, and if available surgical lung biopsy pattern, as assessed by central reviewers, are consistent with diagnosis of IPF 4. Dlco (corrected for Hb): 30%-79% predicted of normal; 5.FVC\>= 50% predicted of normal
Exclusion criteria
1. Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) \> 1.5 x Upper Limit of Normal (ULN) 2. Bilirubin \> 1.5 x ULN; 3. Relevant airways obstruction (i.e. pre-bronchodilator FEV1/FVC \< 0.7); 4. Patient likely to have lung transplantation during study (being on transplantation list is acceptable for participation); 5. Myocardial infarction within 6 months; 6. Unstable angina within 1 month; 7. Bleeding risk (genetic predisposition; fibrinolysis or full-dose therapeutic anticoagulation or high dose antiplatelet therapy; history of hemorrhagic CNS event within 12 months; haemoptysis or haematuria or active gastro-intestinal bleeding or ulcers or major injury or surgery within 3 months); 8. Thrombotic risk (inherited predisposition; history of thrombotic event (including stroke and transient ischemic attacks) within 12 months; 9. International normalised ratio (INR) \> 2, prolongation of prothrombin time (PT) and partial thromboplastin time (PTT) by \> 50% of institutional ULN); 10. N-ACetyl Cystein, prednisone \> 15mg/day or equivalent received within 2 weeks of visit 1; 11. Pirfenidone, azathioprine, cyclophosphamide, cyclosporine A received within 8 weeks of visit 1;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Annual Rate of Decline in Forced Vital Capacity (FVC) Over 52 Weeks. | 52 weeks | Forced vital capacity (FVC) is the total amount of air exhaled during the lung function test. For this endpoint reported means represent the adjusted rate. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to First Acute Idiopathic Pulmonary Fibrosis (IPF) Exacerbation | 52 weeks | Due to rare events, the median of time to event is not calculable, thus the percentages of patients with (IPF) exacerbation are reported and represented as a key secondary endpoint. An acute exacerbation (reported as an AE by the investigator) was defined as follows: Otherwise unexplained clinical features including all of the following: Unexplained worsening or development of dyspnoea within 30 days New diffuse pulmonary infiltrates on chest X-ray, and/or new HRCT parenchymal abnormalities with no pneumothorax or pleural effusion (new ground-glass opacities) since the last visit Exclusion of infection as per routine clinical practice and microbiological studies Exclusion of alternative causes as per routine clinical practice including left heart failure, pulmonary embolism and identifiable cause of acute lung injury. Failure is the proportion of patients with at least one acute IPF exacerbation over 52 weeks, based on all investigator-reported AEs . |
| Absolute Change From Baseline in Forced Vital Capacity (FVC) Over 52 Weeks | Baseline and 52 weeks | Means provided are the adjusted means and are based on all analysed patients in the model (not only patients with a change from baseline to week 52). |
| Relative Change From Baseline in Forced Vital Capacity (FVC) Over 52 Weeks | Baseline and 52 weeks | Percentage change from baseline in FVC over 52 weeks. Means provided are the adjusted means and are based on all analysed patients in the model (not only patients with a change from baseline to week 52). |
| Absolute Change From Baseline in Forced Vital Capacity (FVC) (% Predicted) Over 52 Weeks | Baseline and 52 weeks | Means provided are the adjusted means and are based on all analysed patients in the model (not only patients with a change from baseline to week 52). |
| Relative Change From Baseline in Forced Vital Capacity (FVC) (% Predicted) Over 52 Weeks | Baseline and 52 weeks | Percentage change from baseline in FVC (% predicted) at 52 weeks. Means provided are the adjusted means and are based on all analysed patients in the model (not only patients with a change from baseline to week 52). |
| Absolute Categorical Change From Baseline of FVC (% Predicted) by Categories Over 52 Weeks - 5% Threshold | Baseline and 52 weeks | Absolute categorical change of FVC (% predicted) by categories over 52 weeks - 5% threshold (decrease by \>5%, increase by \>5%, and change within ≤5%). |
| Absolute Categorical Change From Baseline of FVC (% Predicted) by Categories Over 52 Weeks - 10% Threshold | Baseline and 52 weeks | Absolute categorical change of FVC (% predicted) by categories over 52 weeks - 10% threshold (decrease by 10%, increase by \>10%, and change within ≤10%) |
| FVC Responders Using 10% Threshold at 52 Weeks | 52 weeks | FVC responders using 10% threshold at 52 weeks, defined as patients with absolute decline in FVC% predicted no greater than 10% and with an FVC evaluation at 52 weeks. |
| Proportion of FVC Responders Using 5% Threshold at 52 Weeks | 52 weeks | Proportion of FVC responders using 5% threshold at 52 weeks, defined as patients with absolute decline in FVC% predicted no greater than 5% and with an FVC evaluation at 52 weeks. |
| Proportion of SGRQ Responders at 52 Weeks: Patient Reported Outcomes (PROs) | baseline and 52 weeks | Proportion of SGRQ responders at 52 weeks. Responders defined as \<= -4 points change in change from baseline in SGRQ total score at 52 weeks. |
| Change From Baseline in SGRQ Symptom Score at 52 Weeks (Points): Patient Reported Outcomes (PROs) | baseline and 52 weeks | SGRQ Symptom score is a sub-component of SGRQ total score and is concerned with the effect of respiratory symptoms, their frequency and severity. This score calculated as summed weights ranges from 0 to 100 with lower score denoting a better symptom-related quality of life. Means presented are the adjusted means and are based on all analyzed patients in the model (not only patients with a baseline and measurement at week 52). |
| Change From Baseline in SGRQ Impact Score at 52 Weeks (Points): Patient Reported Outcomes (PROs) | baseline and 52 weeks | SGRQ Impact score is a sub-component of SGRQ total score and covers a range of aspects concerned with social functioning and psychological disturbances resulting from airway disease. This score calculated as summed weights ranges from 0 to 100 with lower score denoting a better impact-related quality of life. Means presented are the adjusted means and are based on all analyzed patients in the model (not only patients with a baseline and measurement at week 52). |
| Change From Baseline in SGRQ Activity Score at 52 Weeks (Points): Patient Reported Outcomes (PROs) | baseline and 52 weeks | SGRQ Activity score is a sub-component of SGRQ total score and concerned with activities that cause or are limited by breathlessness. This score calculated as summed weights ranges from 0 to 100 with lower score denoting a better activity-related quality of life. Means presented are the adjusted means and are based on all analyzed patients in the model (not only patients with a baseline and measurement at week 52). |
| Change From Baseline in Saint George's Respiratory Questionnaire (SGRQ) Total Score at 52 Weeks | Baseline and 52 weeks | This is a key secondary endpoint. SGRQ is a health-related quality of life questionnaire divided into 3 components : symptoms, activity and impact. The total score (summed weights) can range from 0 to 100 with a lower score denoting a better health status. Means provided are the adjusted means based on all analyzed patients in the model (not only patients with a baseline and measurement at week 52). |
| Change From Baseline in Shortness of Breath Questionnaire (SOBQ) at 52 Weeks: Patient Reported Outcomes (PROs) | baseline and 52 weeks | Shortness of Breath Questionnaire measures the shortness of breath. It comprises of 24 items. Each item is scored on a scale between 0-5 where 5 represents maximal breathlessness. The responses to all items are summed up to provide the overall score that can range from 0 (best outcome) to 120 (worst outcome). Means presented are the adjusted means and are based on all analyzed patients in the model (not only patients with a baseline and measurement at week 52). |
| Change From Baseline in Cough Symptom Score of the Cough and Sputum Assessment Questionnaire (CASA-Q) Score at 52 Weeks: Patient Reported Outcomes (PROs) | baseline and 52 weeks | The cough domains of the Cough and Sputum Assessment Questionnaire (CASAQ(CD)) assess the frequency and severity of cough and sputum and their impact on everyday life. It contains 4 domains cough/sputum symptom and impact with each scale ranging from 0 to 100 with lower scores indicating higher symptoms/impact levels (worst outcome). Means presented are the adjusted means and are based on all analyzed patients in the model (not only patients with a baseline and measurement at week 52). |
| Change From Baseline in Cough Impact Score of the Cough and Sputum Assessment Questionnaire (CASA-Q) Score at 52 Weeks: Patient Reported Outcomes (PROs) | baseline and 52 weeks | The cough domains of the Cough and Sputum Assessment Questionnaire (CASA- Q) assess the frequency and severity of cough and sputum and their impact on everyday life. It contains 4 domains cough/sputum symptom and impact with each scale ranging from 0 to 100 with lower scores indicating higher symptoms/impact levels (worst outcome). Means presented are the adjusted means and are based on all analyzed patients in the model (not only patients with a baseline and measurement at week 52). |
| Proportion of Patient's Global Impression of Change (PGI-C) Responders at 52 Weeks: Patient Reported Outcomes (PROs) | 52 weeks | Patient's Global Impression of Change (PGI-C) responders are defined as 'Very much better'/ 'Much better'/ 'A little better'/ 'No change'. |
| Change From Baseline in EuroQol 5-Dimensional Quality of Life Questionnaire (EQ-5D) Health State up to 52 Weeks : Patient Reported Outcomes (PROs) | baseline, 12 weeks, 24 weeks and 52 weeks | The EuroQol 5-dimensional Health State is based on a visual analog scale (EQ-VAS) representing the general patient's health state labelled from 100 (best imaginable health state) to 0 (worst imaginable health state). A higher score indicating a better health state. Change from baseline is calculated as the difference between health state at week 12, 24 and 52 respectively and health state at baseline as measured by the scale. |
| Risk of an Acute IPF Exacerbation Over 52 Weeks | 52 weeks | The incidence rate of exacerbations (calculated as the number of patients with at least 1 acute IPF exacerbation divided by the total number of years at risk in years\*100) |
| Time to Death Over 52 Weeks | 52 weeks | Due to rare events, the median of time to event is not calculable, thus the percentages of patients who did or did not experienced death before or at 372 days after randomisation or last contact date (whichever occurs first) are reported. Failure is the proportion of patients who died over 52 weeks (373 days time-period). |
| Time to Death Due to Respiratory Cause Over 52 Weeks (Adjudicated) | 52 weeks | Due to rare events, the median of time to event is not calculable, thus the percentages of participants who did or did not experienced death due to respiratory causes before or at 372 days after randomisation or last contact date (whichever occurs first) are reported. Failure is the the proportion of patients who died due to respiratory causes over 52 weeks (373 days time-period). |
| Time to On-treatment Death | 52 weeks | Due to rare events, the median of time to event is not calculable, thus the percentages of participants who did or did not die before or at last trial medication intake + 28 days were censored at last trial medication intake + 28 days and reported. Failure is the the proportion of patients who died on-treatment. |
| Time to Death or Lung Transplant Over 52 Weeks | 52 weeks | Due to rare events, the median of time to event is not calculable, thus the percentages of participants who did or did not experience event (death or lung transplant) before or at 372 days after randomisation or last contact date (whichever occurs first) are reported. Failure is the proportion of patients who died or had lung transplant over 52 weeks (373 days time-period). |
| Time to Death or Lung Transplant or Qualifying for Lung Transplant Over 52 Weeks. | 52 weeks | Due to rare events, the median of time to event is not calculable, thus the percentages of participants who did or did not experienced death or lung transplant or qualifying for lung transplant over 52 weeks are reported. A patient was considered qualifying for lung transplant by the investigator if he or she fulfilled the following criteria: FVC \<45% predicted or Carbon monoxide diffusion capacity (DL(CO)) \<30% pred or Oxygen saturation on pulse oximetry (SpO2) \<88% at rest, at sea level (to be adapted for other heights). These criteria were evaluated by investigators judgement. Failure is the proportion of patients who died or had lung transplant or qualified for lung transplant over 52 weeks (373 days time-period). |
| Change From Baseline in SpO2 (Oxygen Saturation, Expressed in Percent) at Rest up Over 52 Weeks | baseline and 52 weeks | Means presented are the adjusted means. Adjusted mean is based on all analyzed patients in the model (not only patients with a change from baseline to week 52) |
| Change From Baseline in Carbon Monoxide Diffusion Capacity (DLCO) at Rest Over 52 Weeks | baseline and 52 weeks | Means provided are the adjusted means and are based on all analysed patients in the model (not only patients with a change from baseline to week 52). |
| Change From Baseline in Idiopathic Pulmonary Fibrosis (IPF) Specific Version of SGRQ (SGRQ-I) Total Score at 52 Weeks (Points): Patient Reported Outcomes (PROs) | baseline and 52 weeks | SGRQ-I is the IPF specific version of SGRQ comprises of selected items from the SGRQ divided into three components, Symptoms, Activity and Impact. Each component is scored separately. The weights for all items with a positive responses are summed and the weights from missed items are deducted from the maximum possible weight for the total score. The total score is calculated by dividing the summed weights from positive items in the questionnaire by maximum possible weight for all items in the questionnaire. The total score can range from 0 to 100 with a lower score denoting a better health-related quality of life. Change from baseline is calculated as the difference between total score at week 52 and total score at baseline as measured by the scale. |
Countries
Canada, Chile, China, Finland, France, Germany, Greece, India, Japan, Mexico, Netherlands, Portugal, Russia, South Korea, Spain, Turkey (Türkiye), United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Oral administration of Placebo matching nintedanib soft gelatine capsules | 219 |
| Nintedanib 150 mg Bid Oral administration of soft gelatine capsules of nintedanib 150mg twice daily (bid).
Dose interruption and reduction to 100 mg bid dose were allowed to manage adverse events. | 329 |
| Total | 548 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 30 | 42 |
| Overall Study | Consent withdrawn, not due to AE | 7 | 9 |
| Overall Study | Lost to Follow-up | 1 | 2 |
| Overall Study | Non compliant with protocol | 0 | 2 |
| Overall Study | Not treated | 1 | 2 |
| Overall Study | Reason other than those stated above | 2 | 2 |
Baseline characteristics
| Characteristic | Placebo | Nintedanib 150 mg Bid | Total |
|---|---|---|---|
| Age, Continuous | 67.1 years STANDARD_DEVIATION 7.5 | 66.4 years STANDARD_DEVIATION 7.9 | 66.6 years STANDARD_DEVIATION 7.8 |
| Sex: Female, Male Female | 48 Participants | 73 Participants | 121 Participants |
| Sex: Female, Male Male | 171 Participants | 256 Participants | 427 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 193 / 219 | 308 / 329 |
| serious Total, serious adverse events | 72 / 219 | 98 / 329 |
Outcome results
Primary
Annual Rate of Decline in Forced Vital Capacity (FVC) Over 52 Weeks.
Forced vital capacity (FVC) is the total amount of air exhaled during the lung function test. For this endpoint reported means represent the adjusted rate.
Time frame: 52 weeks
Population: Treated Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Annual Rate of Decline in Forced Vital Capacity (FVC) Over 52 Weeks. | -207.32 mL/year | Standard Error 19.309 |
| Nintedanib 150 mg Bid | Annual Rate of Decline in Forced Vital Capacity (FVC) Over 52 Weeks. | -113.59 mL/year | Standard Error 15.726 |
Comparison: Random coefficient regression with fixed effects for treatment, gender, age, height and random effect of patient specific intercept and time.~A hierarchical procedure was used in order to demonstrate the superiority of nintedanib over placebo for one primary and two key secondary endpoints.~The consecutive steps of the hierarchy were only considered if the previous step was significant at the one-sided 2.5% level and the results were in favour of nintedanib.p-value: 0.000295% CI: [44.78, 142.68]Random coefficient regression
Secondary
Absolute Categorical Change From Baseline of FVC (% Predicted) by Categories Over 52 Weeks - 10% Threshold
Absolute categorical change of FVC (% predicted) by categories over 52 weeks - 10% threshold (decrease by 10%, increase by \>10%, and change within ≤10%)
Time frame: Baseline and 52 weeks
Population: Treated Set (for patients with change from baseline in FVC (% predicted) at Week 52)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Absolute Categorical Change From Baseline of FVC (% Predicted) by Categories Over 52 Weeks - 10% Threshold | Increase > 10% | 0.6 percentage of participants |
| Placebo | Absolute Categorical Change From Baseline of FVC (% Predicted) by Categories Over 52 Weeks - 10% Threshold | Decrease > 10% | 22.2 percentage of participants |
| Placebo | Absolute Categorical Change From Baseline of FVC (% Predicted) by Categories Over 52 Weeks - 10% Threshold | Change within ≤ 10% | 77.2 percentage of participants |
| Nintedanib 150 mg Bid | Absolute Categorical Change From Baseline of FVC (% Predicted) by Categories Over 52 Weeks - 10% Threshold | Increase > 10% | 4.5 percentage of participants |
| Nintedanib 150 mg Bid | Absolute Categorical Change From Baseline of FVC (% Predicted) by Categories Over 52 Weeks - 10% Threshold | Decrease > 10% | 14.9 percentage of participants |
| Nintedanib 150 mg Bid | Absolute Categorical Change From Baseline of FVC (% Predicted) by Categories Over 52 Weeks - 10% Threshold | Change within ≤ 10% | 80.7 percentage of participants |
Secondary
Absolute Categorical Change From Baseline of FVC (% Predicted) by Categories Over 52 Weeks - 5% Threshold
Absolute categorical change of FVC (% predicted) by categories over 52 weeks - 5% threshold (decrease by \>5%, increase by \>5%, and change within ≤5%).
Time frame: Baseline and 52 weeks
Population: Treated Set (for patients with change from baseline in FVC (% predicted) at Week 52)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Absolute Categorical Change From Baseline of FVC (% Predicted) by Categories Over 52 Weeks - 5% Threshold | Decrease > 5% | 52.2 percentage of participants |
| Placebo | Absolute Categorical Change From Baseline of FVC (% Predicted) by Categories Over 52 Weeks - 5% Threshold | Change within ≤ 5% | 45.0 percentage of participants |
| Placebo | Absolute Categorical Change From Baseline of FVC (% Predicted) by Categories Over 52 Weeks - 5% Threshold | Increase > 5% | 2.8 percentage of participants |
| Nintedanib 150 mg Bid | Absolute Categorical Change From Baseline of FVC (% Predicted) by Categories Over 52 Weeks - 5% Threshold | Decrease > 5% | 34.9 percentage of participants |
| Nintedanib 150 mg Bid | Absolute Categorical Change From Baseline of FVC (% Predicted) by Categories Over 52 Weeks - 5% Threshold | Change within ≤ 5% | 50.2 percentage of participants |
| Nintedanib 150 mg Bid | Absolute Categorical Change From Baseline of FVC (% Predicted) by Categories Over 52 Weeks - 5% Threshold | Increase > 5% | 14.9 percentage of participants |
Secondary
Absolute Change From Baseline in Forced Vital Capacity (FVC) Over 52 Weeks
Means provided are the adjusted means and are based on all analysed patients in the model (not only patients with a change from baseline to week 52).
Time frame: Baseline and 52 weeks
Population: Treated Set (Only patients with observed cases (OC) values were analysed)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Absolute Change From Baseline in Forced Vital Capacity (FVC) Over 52 Weeks | -205.03 mL | Standard Error 16.629 |
| Nintedanib 150 mg Bid | Absolute Change From Baseline in Forced Vital Capacity (FVC) Over 52 Weeks | -95.26 mL | Standard Error 14.2 |
Comparison: Based on Mixed Model for Repeated Measures (MMRM), with fixed effects for treatment, visit, gender, age, height, treatment-by-visit, baseline FVC, baseline FVC-by-visit and random effect for patient.p-value: <0.000195% CI: [70.92, 148.62]Mixed Models Analysis
Secondary
Absolute Change From Baseline in Forced Vital Capacity (FVC) (% Predicted) Over 52 Weeks
Means provided are the adjusted means and are based on all analysed patients in the model (not only patients with a change from baseline to week 52).
Time frame: Baseline and 52 weeks
Population: Treated Set (Only patients with observed cases (OC) values were analysed)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Absolute Change From Baseline in Forced Vital Capacity (FVC) (% Predicted) Over 52 Weeks | -6.15 %predicted | Standard Error 0.505 |
| Nintedanib 150 mg Bid | Absolute Change From Baseline in Forced Vital Capacity (FVC) (% Predicted) Over 52 Weeks | -3.09 %predicted | Standard Error 0.433 |
Comparison: Based on Mixed Model for Repeated Measures (MMRM), with fixed effects for treatment, visit, gender, age, height, treatment-by-visit, baseline FVC \[%predicted\], baseline FVC \[%predicted\]-by-visit and random effect for patient.p-value: <0.000195% CI: [1.87, 4.25]Mixed Models Analysis
Secondary
Change From Baseline in Carbon Monoxide Diffusion Capacity (DLCO) at Rest Over 52 Weeks
Means provided are the adjusted means and are based on all analysed patients in the model (not only patients with a change from baseline to week 52).
Time frame: baseline and 52 weeks
Population: Treated Set (Only patients with observed cases (OC) values were analysed)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLCO) at Rest Over 52 Weeks | -0.400 mmol/min/kPa | Standard Error 0.0843 |
| Nintedanib 150 mg Bid | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLCO) at Rest Over 52 Weeks | -0.286 mmol/min/kPa | Standard Error 0.0729 |
Comparison: Mixed Model for Repeated Measures with fixed effects for treatment, visit, gender, age, height, treatment-by-visit, baseline DLCO (HGB Corrected) \[mmol/min/kPa\], baseline DLCO (HGB Corrected) \[mmol/min/kPa\]-by-visit and random effect for patient.p-value: 0.2695% CI: [-0.084, 0.31]Mixed Models Analysis
Secondary
Change From Baseline in Cough Impact Score of the Cough and Sputum Assessment Questionnaire (CASA-Q) Score at 52 Weeks: Patient Reported Outcomes (PROs)
The cough domains of the Cough and Sputum Assessment Questionnaire (CASA- Q) assess the frequency and severity of cough and sputum and their impact on everyday life. It contains 4 domains cough/sputum symptom and impact with each scale ranging from 0 to 100 with lower scores indicating higher symptoms/impact levels (worst outcome). Means presented are the adjusted means and are based on all analyzed patients in the model (not only patients with a baseline and measurement at week 52).
Time frame: baseline and 52 weeks
Population: Treated Set (Only patients with observed cases (OC) values were analysed)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Cough Impact Score of the Cough and Sputum Assessment Questionnaire (CASA-Q) Score at 52 Weeks: Patient Reported Outcomes (PROs) | -4.39 points on a scale | Standard Error 1.209 |
| Nintedanib 150 mg Bid | Change From Baseline in Cough Impact Score of the Cough and Sputum Assessment Questionnaire (CASA-Q) Score at 52 Weeks: Patient Reported Outcomes (PROs) | -2.58 points on a scale | Standard Error 0.991 |
Comparison: Mixed Model for Repeated Measures (MMRM), with fixed effects for treatment, visit, treatment-by-visit, baseline CASA-Q Cough impact score, baseline CASA-Q Cough impact score-by-visit and random effect for patient.p-value: 0.247595% CI: [-1.26, 4.88]Mixed Models Analysis
Secondary
Change From Baseline in Cough Symptom Score of the Cough and Sputum Assessment Questionnaire (CASA-Q) Score at 52 Weeks: Patient Reported Outcomes (PROs)
The cough domains of the Cough and Sputum Assessment Questionnaire (CASAQ(CD)) assess the frequency and severity of cough and sputum and their impact on everyday life. It contains 4 domains cough/sputum symptom and impact with each scale ranging from 0 to 100 with lower scores indicating higher symptoms/impact levels (worst outcome). Means presented are the adjusted means and are based on all analyzed patients in the model (not only patients with a baseline and measurement at week 52).
Time frame: baseline and 52 weeks
Population: Treated Set (Only patients with observed cases (OC) values were analysed)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Cough Symptom Score of the Cough and Sputum Assessment Questionnaire (CASA-Q) Score at 52 Weeks: Patient Reported Outcomes (PROs) | -2.38 points on a scale | Standard Error 1.325 |
| Nintedanib 150 mg Bid | Change From Baseline in Cough Symptom Score of the Cough and Sputum Assessment Questionnaire (CASA-Q) Score at 52 Weeks: Patient Reported Outcomes (PROs) | -0.33 points on a scale | Standard Error 1.087 |
Comparison: Mixed Model for Repeated Measures (MMRM), with fixed effects for treatment, visit, treatment-by-visit, baseline CASA-Q Cough symptoms score, baseline CASA-Q Cough symptoms score-by-visit and random effect for patient.p-value: 0.232695% CI: [-1.31, 5.41]Mixed Models Analysis
Secondary
Change From Baseline in EuroQol 5-Dimensional Quality of Life Questionnaire (EQ-5D) Health State up to 52 Weeks : Patient Reported Outcomes (PROs)
The EuroQol 5-dimensional Health State is based on a visual analog scale (EQ-VAS) representing the general patient's health state labelled from 100 (best imaginable health state) to 0 (worst imaginable health state). A higher score indicating a better health state. Change from baseline is calculated as the difference between health state at week 12, 24 and 52 respectively and health state at baseline as measured by the scale.
Time frame: baseline, 12 weeks, 24 weeks and 52 weeks
Population: Treated Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in EuroQol 5-Dimensional Quality of Life Questionnaire (EQ-5D) Health State up to 52 Weeks : Patient Reported Outcomes (PROs) | 12 weeks (N=207, 306) | -1.48 points on a scale | Standard Deviation 15.6 |
| Placebo | Change From Baseline in EuroQol 5-Dimensional Quality of Life Questionnaire (EQ-5D) Health State up to 52 Weeks : Patient Reported Outcomes (PROs) | 24 weeks (N=204, 297) | -4.86 points on a scale | Standard Deviation 16.94 |
| Placebo | Change From Baseline in EuroQol 5-Dimensional Quality of Life Questionnaire (EQ-5D) Health State up to 52 Weeks : Patient Reported Outcomes (PROs) | 52 weeks (N=178, 265) | -5.60 points on a scale | Standard Deviation 17.67 |
| Nintedanib 150 mg Bid | Change From Baseline in EuroQol 5-Dimensional Quality of Life Questionnaire (EQ-5D) Health State up to 52 Weeks : Patient Reported Outcomes (PROs) | 12 weeks (N=207, 306) | -0.57 points on a scale | Standard Deviation 16.97 |
| Nintedanib 150 mg Bid | Change From Baseline in EuroQol 5-Dimensional Quality of Life Questionnaire (EQ-5D) Health State up to 52 Weeks : Patient Reported Outcomes (PROs) | 24 weeks (N=204, 297) | -1.10 points on a scale | Standard Deviation 16.81 |
| Nintedanib 150 mg Bid | Change From Baseline in EuroQol 5-Dimensional Quality of Life Questionnaire (EQ-5D) Health State up to 52 Weeks : Patient Reported Outcomes (PROs) | 52 weeks (N=178, 265) | -2.52 points on a scale | Standard Deviation 16.95 |
Secondary
Change From Baseline in Idiopathic Pulmonary Fibrosis (IPF) Specific Version of SGRQ (SGRQ-I) Total Score at 52 Weeks (Points): Patient Reported Outcomes (PROs)
SGRQ-I is the IPF specific version of SGRQ comprises of selected items from the SGRQ divided into three components, Symptoms, Activity and Impact. Each component is scored separately. The weights for all items with a positive responses are summed and the weights from missed items are deducted from the maximum possible weight for the total score. The total score is calculated by dividing the summed weights from positive items in the questionnaire by maximum possible weight for all items in the questionnaire. The total score can range from 0 to 100 with a lower score denoting a better health-related quality of life. Change from baseline is calculated as the difference between total score at week 52 and total score at baseline as measured by the scale.
Time frame: baseline and 52 weeks
Population: Treated Set (Only patients with observed cases (OC) values were analysed)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Idiopathic Pulmonary Fibrosis (IPF) Specific Version of SGRQ (SGRQ-I) Total Score at 52 Weeks (Points): Patient Reported Outcomes (PROs) | 5.84 points on a scale | Standard Error 0.921 |
| Nintedanib 150 mg Bid | Change From Baseline in Idiopathic Pulmonary Fibrosis (IPF) Specific Version of SGRQ (SGRQ-I) Total Score at 52 Weeks (Points): Patient Reported Outcomes (PROs) | 2.72 points on a scale | Standard Error 0.757 |
Comparison: Mixed Model for Repeated Measures (MMRM), with fixed effects for treatment, visit, treatment-by-visit, baseline SGRQ-I Total score, baseline SGRQ-I Total score-by-visit and random effect for patient.p-value: 0.008995% CI: [-5.46, -0.79]Mixed Models Analysis
Secondary
Change From Baseline in Saint George's Respiratory Questionnaire (SGRQ) Total Score at 52 Weeks
This is a key secondary endpoint. SGRQ is a health-related quality of life questionnaire divided into 3 components : symptoms, activity and impact. The total score (summed weights) can range from 0 to 100 with a lower score denoting a better health status. Means provided are the adjusted means based on all analyzed patients in the model (not only patients with a baseline and measurement at week 52).
Time frame: Baseline and 52 weeks
Population: Treated Set (Only patients with observed cases (OC) values were analysed)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Saint George's Respiratory Questionnaire (SGRQ) Total Score at 52 Weeks | 5.48 points on a scale | Standard Error 0.891 |
| Nintedanib 150 mg Bid | Change From Baseline in Saint George's Respiratory Questionnaire (SGRQ) Total Score at 52 Weeks | 2.80 points on a scale | Standard Error 0.73 |
Comparison: Mixed Model for Repeated Measures (MMRM), with fixed effects for treatment, visit, treatment-by-visit, baseline SGRQ Total score, baseline SGRQ Total score-by-visit and random effect for patient.p-value: 0.019795% CI: [-4.95, -0.43]Mixed Models Analysis
Secondary
Change From Baseline in SGRQ Activity Score at 52 Weeks (Points): Patient Reported Outcomes (PROs)
SGRQ Activity score is a sub-component of SGRQ total score and concerned with activities that cause or are limited by breathlessness. This score calculated as summed weights ranges from 0 to 100 with lower score denoting a better activity-related quality of life. Means presented are the adjusted means and are based on all analyzed patients in the model (not only patients with a baseline and measurement at week 52).
Time frame: baseline and 52 weeks
Population: Treated Set (Only patients with observed cases (OC) values were analysed)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in SGRQ Activity Score at 52 Weeks (Points): Patient Reported Outcomes (PROs) | 7.20 points on a scale | Standard Error 1.052 |
| Nintedanib 150 mg Bid | Change From Baseline in SGRQ Activity Score at 52 Weeks (Points): Patient Reported Outcomes (PROs) | 3.89 points on a scale | Standard Error 0.863 |
Comparison: Mixed Model for Repeated Measures (MMRM), with fixed effects for treatment, visit, treatment-by-visit, baseline SGRQ Activities component, baseline SGRQ Activities component-by-visit and random effect for patientp-value: 0.015295% CI: [-5.97, -0.64]Mixed Models Analysis
Secondary
Change From Baseline in SGRQ Impact Score at 52 Weeks (Points): Patient Reported Outcomes (PROs)
SGRQ Impact score is a sub-component of SGRQ total score and covers a range of aspects concerned with social functioning and psychological disturbances resulting from airway disease. This score calculated as summed weights ranges from 0 to 100 with lower score denoting a better impact-related quality of life. Means presented are the adjusted means and are based on all analyzed patients in the model (not only patients with a baseline and measurement at week 52).
Time frame: baseline and 52 weeks
Population: Treated Set (Only patients with observed cases (OC) values were analysed)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in SGRQ Impact Score at 52 Weeks (Points): Patient Reported Outcomes (PROs) | 5.93 points on a scale | Standard Error 1.036 |
| Nintedanib 150 mg Bid | Change From Baseline in SGRQ Impact Score at 52 Weeks (Points): Patient Reported Outcomes (PROs) | 2.85 points on a scale | Standard Error 0.852 |
Comparison: Mixed Model for Repeated Measures (MMRM), with fixed effects for treatment, visit, treatment-by-visit, baseline SGRQ impact component, baseline SGRQ impact component-by-visit and random effect for patientp-value: 0.02295% CI: [-5.71, -0.45]Mixed Models Analysis
Secondary
Change From Baseline in SGRQ Symptom Score at 52 Weeks (Points): Patient Reported Outcomes (PROs)
SGRQ Symptom score is a sub-component of SGRQ total score and is concerned with the effect of respiratory symptoms, their frequency and severity. This score calculated as summed weights ranges from 0 to 100 with lower score denoting a better symptom-related quality of life. Means presented are the adjusted means and are based on all analyzed patients in the model (not only patients with a baseline and measurement at week 52).
Time frame: baseline and 52 weeks
Population: Treated Set (Only patients with observed cases (OC) values were analysed)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in SGRQ Symptom Score at 52 Weeks (Points): Patient Reported Outcomes (PROs) | 3.43 points on a scale | Standard Error 1.297 |
| Nintedanib 150 mg Bid | Change From Baseline in SGRQ Symptom Score at 52 Weeks (Points): Patient Reported Outcomes (PROs) | 2.03 points on a scale | Standard Error 1.061 |
Comparison: Mixed Model for Repeated Measures (MMRM), with fixed effects for treatment, visit, treatment-by-visit, baseline SGRQ Symptoms component, baseline SGRQ Symptoms component-by-visit and random effect for patient.p-value: 0.401995% CI: [-4.69, 1.88]Mixed Models Analysis
Secondary
Change From Baseline in Shortness of Breath Questionnaire (SOBQ) at 52 Weeks: Patient Reported Outcomes (PROs)
Shortness of Breath Questionnaire measures the shortness of breath. It comprises of 24 items. Each item is scored on a scale between 0-5 where 5 represents maximal breathlessness. The responses to all items are summed up to provide the overall score that can range from 0 (best outcome) to 120 (worst outcome). Means presented are the adjusted means and are based on all analyzed patients in the model (not only patients with a baseline and measurement at week 52).
Time frame: baseline and 52 weeks
Population: Treated Set (Only patients with observed cases (OC) values were analysed)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Shortness of Breath Questionnaire (SOBQ) at 52 Weeks: Patient Reported Outcomes (PROs) | 9.07 points on a scale | Standard Error 1.3 |
| Nintedanib 150 mg Bid | Change From Baseline in Shortness of Breath Questionnaire (SOBQ) at 52 Weeks: Patient Reported Outcomes (PROs) | 6.69 points on a scale | Standard Error 1.073 |
Comparison: Mixed Model for Repeated Measures (MMRM), with fixed effects for treatment, visit, treatment-by-visit, baseline SOBQ score, baseline SOBQ score-by-visit and random effect for patient.p-value: 0.158795% CI: [-5.68, 0.93]Mixed Models Analysis
Secondary
Change From Baseline in SpO2 (Oxygen Saturation, Expressed in Percent) at Rest up Over 52 Weeks
Means presented are the adjusted means. Adjusted mean is based on all analyzed patients in the model (not only patients with a change from baseline to week 52)
Time frame: baseline and 52 weeks
Population: Treated Set (Only patients with observed cases (OC) values were analysed)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in SpO2 (Oxygen Saturation, Expressed in Percent) at Rest up Over 52 Weeks | -0.66 percent of oxygen saturation | Standard Error 0.174 |
| Nintedanib 150 mg Bid | Change From Baseline in SpO2 (Oxygen Saturation, Expressed in Percent) at Rest up Over 52 Weeks | -0.39 percent of oxygen saturation | Standard Error 0.149 |
Comparison: Mixed Model for Repeated Measures (MMRM), with fixed effects for treatment, visit, gender, age, height, treatment-by-visit, baseline SpO2, baseline SpO2-by-visit and random effect for patient.p-value: 0.203295% CI: [-0.15, 0.69]Mixed Models Analysis
Secondary
FVC Responders Using 10% Threshold at 52 Weeks
FVC responders using 10% threshold at 52 weeks, defined as patients with absolute decline in FVC% predicted no greater than 10% and with an FVC evaluation at 52 weeks.
Time frame: 52 weeks
Population: Treated Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | FVC Responders Using 10% Threshold at 52 Weeks | 63.93 percentage of participants |
| Nintedanib 150 mg Bid | FVC Responders Using 10% Threshold at 52 Weeks | 69.60 percentage of participants |
Comparison: Logistic regression with terms treatment, age, gender, height and baseline FVC % predictedp-value: 0.183395% CI: [0.89, 1.86]Regression, Logistic
Secondary
Proportion of FVC Responders Using 5% Threshold at 52 Weeks
Proportion of FVC responders using 5% threshold at 52 weeks, defined as patients with absolute decline in FVC% predicted no greater than 5% and with an FVC evaluation at 52 weeks.
Time frame: 52 weeks
Population: Treated Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Proportion of FVC Responders Using 5% Threshold at 52 Weeks | 39.27 percentage of participants |
| Nintedanib 150 mg Bid | Proportion of FVC Responders Using 5% Threshold at 52 Weeks | 53.19 percentage of participants |
Comparison: Logistic regression with terms treatment, age, gender, height and baseline FVC % predicted.p-value: 0.001195% CI: [1.26, 2.55]Regression, Logistic
Secondary
Proportion of Patient's Global Impression of Change (PGI-C) Responders at 52 Weeks: Patient Reported Outcomes (PROs)
Patient's Global Impression of Change (PGI-C) responders are defined as 'Very much better'/ 'Much better'/ 'A little better'/ 'No change'.
Time frame: 52 weeks
Population: Treated Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Proportion of Patient's Global Impression of Change (PGI-C) Responders at 52 Weeks: Patient Reported Outcomes (PROs) | 53.88 percentage of participants |
| Nintedanib 150 mg Bid | Proportion of Patient's Global Impression of Change (PGI-C) Responders at 52 Weeks: Patient Reported Outcomes (PROs) | 61.70 percentage of participants |
Comparison: Logistic regression with term treatmentp-value: 0.06995% CI: [0.98, 1.95]Regression, Logistic
Secondary
Proportion of SGRQ Responders at 52 Weeks: Patient Reported Outcomes (PROs)
Proportion of SGRQ responders at 52 weeks. Responders defined as \<= -4 points change in change from baseline in SGRQ total score at 52 weeks.
Time frame: baseline and 52 weeks
Population: Treated Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Proportion of SGRQ Responders at 52 Weeks: Patient Reported Outcomes (PROs) | 16.89 percentage of participants |
| Nintedanib 150 mg Bid | Proportion of SGRQ Responders at 52 Weeks: Patient Reported Outcomes (PROs) | 25.23 percentage of participants |
Comparison: Logistic regression with terms treatment, baseline SGRQ total scorep-value: 0.021895% CI: [1.08, 2.57]Regression, Logistic
Secondary
Relative Change From Baseline in Forced Vital Capacity (FVC) Over 52 Weeks
Percentage change from baseline in FVC over 52 weeks. Means provided are the adjusted means and are based on all analysed patients in the model (not only patients with a change from baseline to week 52).
Time frame: Baseline and 52 weeks
Population: Treated Set (Only patients with observed cases (OC) values were analysed)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Relative Change From Baseline in Forced Vital Capacity (FVC) Over 52 Weeks | -8.14 percent change | Standard Error 0.62 |
| Nintedanib 150 mg Bid | Relative Change From Baseline in Forced Vital Capacity (FVC) Over 52 Weeks | -3.90 percent change | Standard Error 0.528 |
Comparison: Based on Mixed Model for Repeated Measures (MMRM), with fixed effects for treatment, visit, gender, age, height, treatment-by-visit, baseline FVC, baseline FVC-by-visit and random effect for patient.p-value: <0.000195% CI: [2.78, 5.69]Mixed Models Analysis
Secondary
Relative Change From Baseline in Forced Vital Capacity (FVC) (% Predicted) Over 52 Weeks
Percentage change from baseline in FVC (% predicted) at 52 weeks. Means provided are the adjusted means and are based on all analysed patients in the model (not only patients with a change from baseline to week 52).
Time frame: Baseline and 52 weeks
Population: Treated Set (Only patients with observed cases (OC) values were analysed)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Relative Change From Baseline in Forced Vital Capacity (FVC) (% Predicted) Over 52 Weeks | -8.13 percent change | Standard Error 0.614 |
| Nintedanib 150 mg Bid | Relative Change From Baseline in Forced Vital Capacity (FVC) (% Predicted) Over 52 Weeks | -3.92 percent change | Standard Error 0.525 |
Comparison: Based on Mixed Model for Repeated Measures (MMRM), with fixed effects for treatment, visit, gender, age, height, treatment-by-visit, baseline FVC \[%predicted\], baseline FVC \[%predicted\]-by-visit and random effect for patient.p-value: <0.000195% CI: [2.76, 5.67]Mixed Models Analysis
Secondary
Risk of an Acute IPF Exacerbation Over 52 Weeks
The incidence rate of exacerbations (calculated as the number of patients with at least 1 acute IPF exacerbation divided by the total number of years at risk in years\*100)
Time frame: 52 weeks
Population: Treated Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Risk of an Acute IPF Exacerbation Over 52 Weeks | 10.2 Participants/Year *100 |
| Nintedanib 150 mg Bid | Risk of an Acute IPF Exacerbation Over 52 Weeks | 3.9 Participants/Year *100 |
Comparison: The log of the risk ratio was assumed to follow a normal distribution with mean 0 and variance equal to the sum of the reciprocals of the number of patients with at least one exacerbation in each treatment arm.p-value: 0.00795% CI: [0.19, 0.77]Normal distribution
Secondary
Time to Death Due to Respiratory Cause Over 52 Weeks (Adjudicated)
Due to rare events, the median of time to event is not calculable, thus the percentages of participants who did or did not experienced death due to respiratory causes before or at 372 days after randomisation or last contact date (whichever occurs first) are reported. Failure is the the proportion of patients who died due to respiratory causes over 52 weeks (373 days time-period).
Time frame: 52 weeks
Population: Treated Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Time to Death Due to Respiratory Cause Over 52 Weeks (Adjudicated) | Failure | 5.0 percentage of participants |
| Placebo | Time to Death Due to Respiratory Cause Over 52 Weeks (Adjudicated) | Censored | 95.0 percentage of participants |
| Nintedanib 150 mg Bid | Time to Death Due to Respiratory Cause Over 52 Weeks (Adjudicated) | Failure | 4.3 percentage of participants |
| Nintedanib 150 mg Bid | Time to Death Due to Respiratory Cause Over 52 Weeks (Adjudicated) | Censored | 95.7 percentage of participants |
Comparison: Hazard ratio is based on Cox´s regression model with terms for treatment, gender, age and height.p-value: 0.665495% CI: [0.39, 1.9]Log Rank
Secondary
Time to Death or Lung Transplant or Qualifying for Lung Transplant Over 52 Weeks.
Due to rare events, the median of time to event is not calculable, thus the percentages of participants who did or did not experienced death or lung transplant or qualifying for lung transplant over 52 weeks are reported. A patient was considered qualifying for lung transplant by the investigator if he or she fulfilled the following criteria: FVC \<45% predicted or Carbon monoxide diffusion capacity (DL(CO)) \<30% pred or Oxygen saturation on pulse oximetry (SpO2) \<88% at rest, at sea level (to be adapted for other heights). These criteria were evaluated by investigators judgement. Failure is the proportion of patients who died or had lung transplant or qualified for lung transplant over 52 weeks (373 days time-period).
Time frame: 52 weeks
Population: Treated Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Time to Death or Lung Transplant or Qualifying for Lung Transplant Over 52 Weeks. | Censored | 76.3 percentage of participants |
| Placebo | Time to Death or Lung Transplant or Qualifying for Lung Transplant Over 52 Weeks. | Failure | 23.7 percentage of participants |
| Nintedanib 150 mg Bid | Time to Death or Lung Transplant or Qualifying for Lung Transplant Over 52 Weeks. | Failure | 19.5 percentage of participants |
| Nintedanib 150 mg Bid | Time to Death or Lung Transplant or Qualifying for Lung Transplant Over 52 Weeks. | Censored | 80.5 percentage of participants |
Comparison: Hazard ratio is based on Cox´s regression model with terms for treatment, gender, age and height.p-value: 0.212395% CI: [0.55, 1.16]Log Rank
Secondary
Time to Death or Lung Transplant Over 52 Weeks
Due to rare events, the median of time to event is not calculable, thus the percentages of participants who did or did not experience event (death or lung transplant) before or at 372 days after randomisation or last contact date (whichever occurs first) are reported. Failure is the proportion of patients who died or had lung transplant over 52 weeks (373 days time-period).
Time frame: 52 weeks
Population: Treated Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Time to Death or Lung Transplant Over 52 Weeks | Failure | 10.0 percentage of participants |
| Placebo | Time to Death or Lung Transplant Over 52 Weeks | Censored | 90.0 percentage of participants |
| Nintedanib 150 mg Bid | Time to Death or Lung Transplant Over 52 Weeks | Failure | 6.7 percentage of participants |
| Nintedanib 150 mg Bid | Time to Death or Lung Transplant Over 52 Weeks | Censored | 93.3 percentage of participants |
Comparison: Hazard ratio is based on Cox´s regression model with terms for treatment, gender, age and height.p-value: 0.166495% CI: [0.37, 1.21]Log Rank
Secondary
Time to Death Over 52 Weeks
Due to rare events, the median of time to event is not calculable, thus the percentages of patients who did or did not experienced death before or at 372 days after randomisation or last contact date (whichever occurs first) are reported. Failure is the proportion of patients who died over 52 weeks (373 days time-period).
Time frame: 52 weeks
Population: Treated Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Time to Death Over 52 Weeks | Failure | 9.1 percentage of participants |
| Placebo | Time to Death Over 52 Weeks | Censored | 90.9 percentage of participants |
| Nintedanib 150 mg Bid | Time to Death Over 52 Weeks | Failure | 6.7 percentage of participants |
| Nintedanib 150 mg Bid | Time to Death Over 52 Weeks | Censored | 93.3 percentage of participants |
Comparison: Hazard ratio is based on a Cox´s regression model with terms for treatment, gender, age and height.p-value: 0.299595% CI: [0.4, 1.35]Log Rank
Secondary
Time to First Acute Idiopathic Pulmonary Fibrosis (IPF) Exacerbation
Due to rare events, the median of time to event is not calculable, thus the percentages of patients with (IPF) exacerbation are reported and represented as a key secondary endpoint. An acute exacerbation (reported as an AE by the investigator) was defined as follows: Otherwise unexplained clinical features including all of the following: Unexplained worsening or development of dyspnoea within 30 days New diffuse pulmonary infiltrates on chest X-ray, and/or new HRCT parenchymal abnormalities with no pneumothorax or pleural effusion (new ground-glass opacities) since the last visit Exclusion of infection as per routine clinical practice and microbiological studies Exclusion of alternative causes as per routine clinical practice including left heart failure, pulmonary embolism and identifiable cause of acute lung injury. Failure is the proportion of patients with at least one acute IPF exacerbation over 52 weeks, based on all investigator-reported AEs .
Time frame: 52 weeks
Population: Treated Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Time to First Acute Idiopathic Pulmonary Fibrosis (IPF) Exacerbation | Failure | 9.6 percentage of participants |
| Placebo | Time to First Acute Idiopathic Pulmonary Fibrosis (IPF) Exacerbation | Censored | 90.4 percentage of participants |
| Nintedanib 150 mg Bid | Time to First Acute Idiopathic Pulmonary Fibrosis (IPF) Exacerbation | Failure | 3.6 percentage of participants |
| Nintedanib 150 mg Bid | Time to First Acute Idiopathic Pulmonary Fibrosis (IPF) Exacerbation | Censored | 96.4 percentage of participants |
Comparison: Hazard Ratio is based on a Cox's regression model with terms for treatment, gender, age and height.p-value: 0.00595% CI: [0.19, 0.77]Log Rank
Secondary
Time to On-treatment Death
Due to rare events, the median of time to event is not calculable, thus the percentages of participants who did or did not die before or at last trial medication intake + 28 days were censored at last trial medication intake + 28 days and reported. Failure is the the proportion of patients who died on-treatment.
Time frame: 52 weeks
Population: Treated Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Time to On-treatment Death | Failure | 7.8 percentage of participants |
| Placebo | Time to On-treatment Death | Censored | 92.2 percentage of participants |
| Nintedanib 150 mg Bid | Time to On-treatment Death | Failure | 4.9 percentage of participants |
| Nintedanib 150 mg Bid | Time to On-treatment Death | Censored | 95.1 percentage of participants |
Comparison: Hazard ratio is based on a Cox´s regression model with terms for treatment, gender, age and height.p-value: 0.220995% CI: [0.34, 1.35]Log Rank