Safety and Efficacy of BIBF 1120 at High Dose in Idiopathic Pulmonary Fibrosis Patients II
- Registration Number
- NCT01335477
- Lead Sponsor
- Boehringer Ingelheim
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 551
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description placebo placebo patient receives capsules identical to those containing active drug BIBF 1120 BIBF 1120 patient receives capsules containing BIBF 1120 twice a day
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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 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 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.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).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).
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.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).
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 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).
Trial Locations
- Locations (108)
1199.34.10080 Boehringer Ingelheim Investigational Site
🇺🇸Stamford, Connecticut, United States
1199.34.10070 Boehringer Ingelheim Investigational Site
🇺🇸Portland, Oregon, United States
1199.34.10074 Boehringer Ingelheim Investigational Site
🇺🇸Durham, North Carolina, United States
1199.34.10086 Boehringer Ingelheim Investigational Site
🇺🇸San Francisco, California, United States
1199.34.10084 Boehringer Ingelheim Investigational Site
🇺🇸Salt Lake City, Utah, United States
1199.34.82001 Boehringer Ingelheim Investigational Site
🇰🇷Seoul, Korea, Republic of
1199.34.33005 Boehringer Ingelheim Investigational Site
🇫🇷Lyon Cedex, France
1199.34.10073 Boehringer Ingelheim Investigational Site
🇺🇸Madison, Wisconsin, United States
1199.34.02002 Boehringer Ingelheim Investigational Site
🇨🇦Hamilton, Ontario, Canada
1199.34.33007 Boehringer Ingelheim Investigational Site
🇫🇷Marseille, France
1199.34.10060 Boehringer Ingelheim Investigational Site
🇺🇸San Antonio, Texas, United States
1199.34.02003 Boehringer Ingelheim Investigational Site
🇨🇦Halifax, Nova Scotia, Canada
1199.34.10085 Boehringer Ingelheim Investigational Site
🇺🇸Albany, New York, United States
1199.34.56001 Boehringer Ingelheim Investigational Site
🇨🇱Santiago de Chile, Chile
1199.34.86051 Boehringer Ingelheim Investigational Site
🇨🇳Shenyang, China
1199.34.33006 Boehringer Ingelheim Investigational Site
🇫🇷Toulouse cedex 9, France
1199.34.10067 Boehringer Ingelheim Investigational Site
🇺🇸Chesterfield, Missouri, United States
1199.34.10095 Boehringer Ingelheim Investigational Site
🇺🇸Longview, Texas, United States
1199.34.02001 Boehringer Ingelheim Investigational Site
🇨🇦Calgary, Alberta, Canada
1199.34.86054 Boehringer Ingelheim Investigational Site
🇨🇳Shanghai, China
1199.34.86053 Boehringer Ingelheim Investigational Site
🇨🇳Shenyang, China
1199.34.49010 Boehringer Ingelheim Investigational Site
🇩🇪Berlin-Buch, Germany
1199.34.49002 Boehringer Ingelheim Investigational Site
🇩🇪Berlin, Germany
1199.34.86056 Boehringer Ingelheim Investigational Site
🇨🇳Beijing, China
1199.34.10066 Boehringer Ingelheim Investigational Site
🇺🇸Lebanon, New Hampshire, United States
1199.34.86057 Boehringer Ingelheim Investigational Site
🇨🇳Yinchuan, China
1199.34.49004 Boehringer Ingelheim Investigational Site
🇩🇪Münster, Germany
1199.34.49003 Boehringer Ingelheim Investigational Site
🇩🇪Bad Berka, Germany
1199.34.90001 Boehringer Ingelheim Investigational Site
🇹🇷Istanbul, Turkey
1199.34.10090 Boehringer Ingelheim Investigational Site
🇺🇸Lexington, Kentucky, United States
1199.34.10075 Boehringer Ingelheim Investigational Site
🇺🇸Chicago, Illinois, United States
1199.34.10093 Boehringer Ingelheim Investigational Site
🇺🇸Santa Barbara, California, United States
1199.34.10078 Boehringer Ingelheim Investigational Site
🇺🇸Scottsdale, Arizona, United States
1199.34.10083 Boehringer Ingelheim Investigational Site
🇺🇸Torrance, California, United States
1199.34.10077 Boehringer Ingelheim Investigational Site
🇺🇸Stanford, California, United States
1199.34.10087 Boehringer Ingelheim Investigational Site
🇺🇸South Miami, Florida, United States
1199.34.10100 Boehringer Ingelheim Investigational Site
🇺🇸Austell, Georgia, United States
1199.34.10069 Boehringer Ingelheim Investigational Site
🇺🇸Olathe, Kansas, United States
1199.34.10079 Boehringer Ingelheim Investigational Site
🇺🇸Rochester, Minnesota, United States
1199.34.10089 Boehringer Ingelheim Investigational Site
🇺🇸Philadelphia, Pennsylvania, United States
1199.34.10088 Boehringer Ingelheim Investigational Site
🇺🇸Toledo, Ohio, United States
1199.34.10064 Boehringer Ingelheim Investigational Site
🇺🇸Philadelphia, Pennsylvania, United States
1199.34.10082 Boehringer Ingelheim Investigational Site
🇺🇸Charleston, South Carolina, United States
1199.34.10101 Boehringer Ingelheim Investigational Site
🇺🇸Colchester, Vermont, United States
1199.34.86052 Boehringer Ingelheim Investigational Site
🇨🇳Shanghai, China
1199.34.86055 Boehringer Ingelheim Investigational Site
🇨🇳Shanghai, China
1199.34.86058 Boehringer Ingelheim Investigational Site
🇨🇳Shanghai, China
1199.34.35801 Boehringer Ingelheim Investigational Site
🇫🇮Helsinki, Finland
1199.34.33004 Boehringer Ingelheim Investigational Site
🇫🇷Dijon Cedex, France
1199.34.33003 Boehringer Ingelheim Investigational Site
🇫🇷Lille Cedex, France
1199.34.33002 Boehringer Ingelheim Investigational Site
🇫🇷Montpellier cedex 5, France
1199.34.49005 Boehringer Ingelheim Investigational Site
🇩🇪Coswig, Germany
1199.34.49001 Boehringer Ingelheim Investigational Site
🇩🇪Essen, Germany
1199.34.49007 Boehringer Ingelheim Investigational Site
🇩🇪Greifswald, Germany
1199.34.49006 Boehringer Ingelheim Investigational Site
🇩🇪München, Germany
1199.34.49011 Boehringer Ingelheim Investigational Site
🇩🇪Köln, Germany
1199.34.30005 Boehringer Ingelheim Investigational Site
🇬🇷Athens, Greece
1199.34.30001 Boehringer Ingelheim Investigational Site
🇬🇷Heraklion, Greece
1199.34.30004 Boehringer Ingelheim Investigational Site
🇬🇷Larisa, Greece
1199.34.30002 Boehringer Ingelheim Investigational Site
🇬🇷Maroussi, Athens, Greece
1199.34.91053 Boehringer Ingelheim Investigational Site
🇮🇳Banglore, India
1199.34.91051 Boehringer Ingelheim Investigational Site
🇮🇳Ahmedabad, India
1199.34.30003 Boehringer Ingelheim Investigational Site
🇬🇷Nikaia, Greece
1199.34.91056 Boehringer Ingelheim Investigational Site
🇮🇳Jaipur, India
1199.34.91054 Boehringer Ingelheim Investigational Site
🇮🇳Pune, India
1199.34.91055 Boehringer Ingelheim Investigational Site
🇮🇳Pune, India
1199.34.81059 Boehringer Ingelheim Investigational Site
🇯🇵Himeji, Hyogo, Japan
1199.34.81063 Boehringer Ingelheim Investigational Site
🇯🇵Kawasaki, Kanagawa, Japan
1199.34.81060 Boehringer Ingelheim Investigational Site
🇯🇵Kobe, Hyogo, Japan
1199.34.81051 Boehringer Ingelheim Investigational Site
🇯🇵Minato-ku, Tokyo, Japan
1199.34.81054 Boehringer Ingelheim Investigational Site
🇯🇵Nagoya, Aichi, Japan
1199.34.81058 Boehringer Ingelheim Investigational Site
🇯🇵Osaka-Sayama, Osaka, Japan
1199.34.81053 Boehringer Ingelheim Investigational Site
🇯🇵Seto, Aichi, Japan
1199.34.81055 Boehringer Ingelheim Investigational Site
🇯🇵Ogaki, Gifu, Japan
1199.34.81057 Boehringer Ingelheim Investigational Site
🇯🇵Sakai, Osaka, Japan
1199.34.81052 Boehringer Ingelheim Investigational Site
🇯🇵Shinjuku-ku, Tokyo, Japan
1199.34.81056 Boehringer Ingelheim Investigational Site
🇯🇵Tenri, Nara, Japan
1199.34.81062 Boehringer Ingelheim Investigational Site
🇯🇵Tokushima, Tokushima, Japan
1199.34.81061 Boehringer Ingelheim Investigational Site
🇯🇵Yonago, Tottori, Japan
1199.34.82002 Boehringer Ingelheim Investigational Site
🇰🇷Bucheon, Korea, Republic of
1199.34.82003 Boehringer Ingelheim Investigational Site
🇰🇷Seoul, Korea, Republic of
1199.34.82006 Boehringer Ingelheim Investigational Site
🇰🇷Seoul, Korea, Republic of
1199.34.82007 Boehringer Ingelheim Investigational Site
🇰🇷Seoul, Korea, Republic of
1199.34.52001 Boehringer Ingelheim Investigational Site
🇲🇽Mexico DF, Mexico
1199.34.31002 Boehringer Ingelheim Investigational Site
🇳🇱Amsterdam, Netherlands
1199.34.31001 Boehringer Ingelheim Investigational Site
🇳🇱Nieuwegein, Netherlands
1199.34.35105 Boehringer Ingelheim Investigational Site
🇵🇹Coimbra, Portugal
1199.34.31003 Boehringer Ingelheim Investigational Site
🇳🇱Rotterdam, Netherlands
1199.34.35107 Boehringer Ingelheim Investigational Site
🇵🇹Amadora, Portugal
1199.34.35102 Boehringer Ingelheim Investigational Site
🇵🇹Lisboa, Portugal
1199.34.35103 Boehringer Ingelheim Investigational Site
🇵🇹Lisboa, Portugal
1199.34.35101 Boehringer Ingelheim Investigational Site
🇵🇹Porto, Portugal
1199.34.35106 Boehringer Ingelheim Investigational Site
🇵🇹Vila Nova de Gaia, Portugal
1199.34.07003 Boehringer Ingelheim Investigational Site
🇷🇺St. Petersburg, Russian Federation
1199.34.07001 Boehringer Ingelheim Investigational Site
🇷🇺Kazan, Russian Federation
1199.34.34001 Boehringer Ingelheim Investigational Site
🇪🇸Barcelona, Spain
1199.34.34005 Boehringer Ingelheim Investigational Site
🇪🇸Hospitalet de Llobregat, Spain
1199.34.34004 Boehringer Ingelheim Investigational Site
🇪🇸Barcelona, Spain
1199.34.34003 Boehringer Ingelheim Investigational Site
🇪🇸Barcelona, Spain
1199.34.34009 Boehringer Ingelheim Investigational Site
🇪🇸Madrid, Spain
1199.34.34008 Boehringer Ingelheim Investigational Site
🇪🇸Sevilla, Spain
1199.34.90005 Boehringer Ingelheim Investigational Site
🇹🇷Istanbul, Turkey
1199.34.90003 Boehringer Ingelheim Investigational Site
🇹🇷Ankara, Turkey
1199.34.90002 Boehringer Ingelheim Investigational Site
🇹🇷Izmir, Turkey
1199.34.90004 Boehringer Ingelheim Investigational Site
🇹🇷Izmir, Turkey
1199.34.10092 Boehringer Ingelheim Investigational Site
🇺🇸Jamaica, New York, United States
1199.34.49009 Boehringer Ingelheim Investigational Site
🇩🇪Immenhausen, Germany
1199.34.82004 Boehringer Ingelheim Investigational Site
🇰🇷Incheon, Korea, Republic of