Clinical trial NCT01335477: Safety and Efficacy of BIBF 1120 at High Dose in Idiopathic Pulmonary Fibrosis Patients II
Official title: A 52 Weeks, Double Blind, Randomized, Placebo-controlled Trial Evaluating the Effect of Oral BIBF 1120, 150 mg Twice Daily, on Annual Forced Vital Capacity Decline, in Patients With Idiopathic Pulmonary Fibrosis (IPF)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pulmonary Fibrosis
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2011-04-14
Enrollment: 551
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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;

Primary outcomes:
measure: Annual Rate of Decline in Forced Vital Capacity (FVC) Over 52 Weeks.
timeFrame: 52 weeks
Secondary outcomes:
measure: Change From Baseline in Saint George's Respiratory Questionnaire (SGRQ) Total Score at 52 Weeks
timeFrame: Baseline and 52 weeks
measure: Time to First Acute Idiopathic Pulmonary Fibrosis (IPF) Exacerbation
timeFrame: 52 weeks
measure: Absolute Change From Baseline in Forced Vital Capacity (FVC) Over 52 Weeks
timeFrame: Baseline and 52 weeks
measure: Relative Change From Baseline in Forced Vital Capacity (FVC) Over 52 Weeks
timeFrame: Baseline and 52 weeks
measure: Absolute Change From Baseline in Forced Vital Capacity (FVC) (% Predicted) Over 52 Weeks
timeFrame: Baseline and 52 weeks
measure: Relative Change From Baseline in Forced Vital Capacity (FVC) (% Predicted) Over 52 Weeks
timeFrame: Baseline and 52 weeks
measure: Absolute Categorical Change From Baseline of FVC (% Predicted) by Categories Over 52 Weeks - 5% Threshold
timeFrame: Baseline and 52 weeks
measure: Absolute Categorical Change From Baseline of FVC (% Predicted) by Categories Over 52 Weeks - 10% Threshold
timeFrame: Baseline and 52 weeks
measure: FVC Responders Using 10% Threshold at 52 Weeks
timeFrame: 52 weeks
measure: Proportion of FVC Responders Using 5% Threshold at 52 Weeks
timeFrame: 52 weeks
measure: Proportion of SGRQ Responders at 52 Weeks: Patient Reported Outcomes (PROs)
timeFrame: baseline and 52 weeks
measure: Change From Baseline in SGRQ Symptom Score at 52 Weeks (Points): Patient Reported Outcomes (PROs)
timeFrame: baseline and 52 weeks
measure: Change From Baseline in SGRQ Impact Score at 52 Weeks (Points): Patient Reported Outcomes (PROs)
timeFrame: baseline and 52 weeks
measure: Change From Baseline in SGRQ Activity Score at 52 Weeks (Points): Patient Reported Outcomes (PROs)
timeFrame: baseline and 52 weeks
measure: Change From Baseline in Idiopathic Pulmonary Fibrosis (IPF) Specific Version of SGRQ (SGRQ-I) Total Score at 52 Weeks (Points): Patient Reported Outcomes (PROs)
timeFrame: baseline and 52 weeks
measure: Change From Baseline in Shortness of Breath Questionnaire (SOBQ) at 52 Weeks: Patient Reported Outcomes (PROs)
timeFrame: baseline and 52 weeks
measure: Change From Baseline in Cough Symptom Score of the Cough and Sputum Assessment Questionnaire (CASA-Q) Score at 52 Weeks: Patient Reported Outcomes (PROs)
timeFrame: baseline and 52 weeks
measure: Change From Baseline in Cough Impact Score of the Cough and Sputum Assessment Questionnaire (CASA-Q) Score at 52 Weeks: Patient Reported Outcomes (PROs)
timeFrame: baseline and 52 weeks
measure: Proportion of Patient's Global Impression of Change (PGI-C) Responders at 52 Weeks: Patient Reported Outcomes (PROs)
timeFrame: 52 weeks
measure: Change From Baseline in EuroQol 5-Dimensional Quality of Life Questionnaire (EQ-5D) Health State up to 52 Weeks : Patient Reported Outcomes (PROs)
timeFrame: baseline, 12 weeks, 24 weeks and 52 weeks
measure: Risk of an Acute IPF Exacerbation Over 52 Weeks
timeFrame: 52 weeks
measure: Time to Death Over 52 Weeks
timeFrame: 52 weeks
measure: Time to Death Due to Respiratory Cause Over 52 Weeks (Adjudicated)
timeFrame: 52 weeks
measure: Time to On-treatment Death
timeFrame: 52 weeks
measure: Time to Death or Lung Transplant Over 52 Weeks
timeFrame: 52 weeks
measure: Time to Death or Lung Transplant or Qualifying for Lung Transplant Over 52 Weeks.
timeFrame: 52 weeks
measure: Change From Baseline in SpO2 (Oxygen Saturation, Expressed in Percent) at Rest up Over 52 Weeks
timeFrame: baseline and 52 weeks
measure: Change From Baseline in Carbon Monoxide Diffusion Capacity (DLCO) at Rest Over 52 Weeks
timeFrame: baseline and 52 weeks
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: 1199.34.10078 Boehringer Ingelheim Investigational Site
state: Arizona
city: San Francisco
country: United States
facility: 1199.34.10086 Boehringer Ingelheim Investigational Site
state: California
city: Santa Barbara
country: United States
facility: 1199.34.10093 Boehringer Ingelheim Investigational Site
state: California
city: Stanford
country: United States
facility: 1199.34.10077 Boehringer Ingelheim Investigational Site
state: California
city: Torrance
country: United States
facility: 1199.34.10083 Boehringer Ingelheim Investigational Site
state: California
city: Stamford
country: United States
facility: 1199.34.10080 Boehringer Ingelheim Investigational Site
state: Connecticut
city: South Miami
country: United States
facility: 1199.34.10087 Boehringer Ingelheim Investigational Site
state: Florida
city: Austell
country: United States
facility: 1199.34.10100 Boehringer Ingelheim Investigational Site
state: Georgia
city: Chicago
country: United States
facility: 1199.34.10075 Boehringer Ingelheim Investigational Site
state: Illinois
city: Olathe
country: United States
facility: 1199.34.10069 Boehringer Ingelheim Investigational Site
state: Kansas
city: Lexington
country: United States
facility: 1199.34.10090 Boehringer Ingelheim Investigational Site
state: Kentucky
city: Rochester
country: United States
facility: 1199.34.10079 Boehringer Ingelheim Investigational Site
state: Minnesota
city: Chesterfield
country: United States
facility: 1199.34.10067 Boehringer Ingelheim Investigational Site
state: Missouri
city: Lebanon
country: United States
facility: 1199.34.10066 Boehringer Ingelheim Investigational Site
state: New Hampshire
city: Albany
country: United States
facility: 1199.34.10085 Boehringer Ingelheim Investigational Site
state: New York
city: Jamaica
country: United States
facility: 1199.34.10092 Boehringer Ingelheim Investigational Site
state: New York
city: Durham
country: United States
facility: 1199.34.10074 Boehringer Ingelheim Investigational Site
state: North Carolina
city: Toledo
country: United States
facility: 1199.34.10088 Boehringer Ingelheim Investigational Site
state: Ohio
city: Portland
country: United States
facility: 1199.34.10070 Boehringer Ingelheim Investigational Site
state: Oregon
city: Philadelphia
country: United States
facility: 1199.34.10064 Boehringer Ingelheim Investigational Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: 1199.34.10089 Boehringer Ingelheim Investigational Site
state: Pennsylvania
city: Charleston
country: United States
facility: 1199.34.10082 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Longview
country: United States
facility: 1199.34.10095 Boehringer Ingelheim Investigational Site
state: Texas
city: San Antonio
country: United States
facility: 1199.34.10060 Boehringer Ingelheim Investigational Site
state: Texas
city: Salt Lake City
country: United States
facility: 1199.34.10084 Boehringer Ingelheim Investigational Site
state: Utah
city: Colchester
country: United States
facility: 1199.34.10101 Boehringer Ingelheim Investigational Site
state: Vermont
city: Madison
country: United States
facility: 1199.34.10073 Boehringer Ingelheim Investigational Site
state: Wisconsin
city: Calgary
country: Canada
facility: 1199.34.02001 Boehringer Ingelheim Investigational Site
state: Alberta
city: Halifax
country: Canada
facility: 1199.34.02003 Boehringer Ingelheim Investigational Site
state: Nova Scotia
city: Hamilton
country: Canada
facility: 1199.34.02002 Boehringer Ingelheim Investigational Site
state: Ontario
city: Santiago de Chile
country: Chile
facility: 1199.34.56001 Boehringer Ingelheim Investigational Site
city: Beijing
country: China
facility: 1199.34.86056 Boehringer Ingelheim Investigational Site
city: Shanghai
country: China
facility: 1199.34.86052 Boehringer Ingelheim Investigational Site
city: Shanghai
country: China
facility: 1199.34.86054 Boehringer Ingelheim Investigational Site
city: Shanghai
country: China
facility: 1199.34.86055 Boehringer Ingelheim Investigational Site
city: Shanghai
country: China
facility: 1199.34.86058 Boehringer Ingelheim Investigational Site
city: Shenyang
country: China
facility: 1199.34.86051 Boehringer Ingelheim Investigational Site
city: Shenyang
country: China
facility: 1199.34.86053 Boehringer Ingelheim Investigational Site
city: Yinchuan
country: China
facility: 1199.34.86057 Boehringer Ingelheim Investigational Site
city: Helsinki
country: Finland
facility: 1199.34.35801 Boehringer Ingelheim Investigational Site
city: Dijon Cedex
country: France
facility: 1199.34.33004 Boehringer Ingelheim Investigational Site
city: Lille Cedex
country: France
facility: 1199.34.33003 Boehringer Ingelheim Investigational Site
city: Lyon Cedex
country: France
facility: 1199.34.33005 Boehringer Ingelheim Investigational Site
city: Marseille
country: France
facility: 1199.34.33007 Boehringer Ingelheim Investigational Site
city: Montpellier cedex 5
country: France
facility: 1199.34.33002 Boehringer Ingelheim Investigational Site
city: Toulouse cedex 9
country: France
facility: 1199.34.33006 Boehringer Ingelheim Investigational Site
city: Bad Berka
country: Germany
facility: 1199.34.49003 Boehringer Ingelheim Investigational Site
city: Berlin-Buch
country: Germany
facility: 1199.34.49010 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 1199.34.49002 Boehringer Ingelheim Investigational Site
city: Coswig
country: Germany
facility: 1199.34.49005 Boehringer Ingelheim Investigational Site
city: Essen
country: Germany
facility: 1199.34.49001 Boehringer Ingelheim Investigational Site
city: Greifswald
country: Germany
facility: 1199.34.49007 Boehringer Ingelheim Investigational Site
city: Immenhausen
country: Germany
facility: 1199.34.49009 Boehringer Ingelheim Investigational Site
city: Köln
country: Germany
facility: 1199.34.49011 Boehringer Ingelheim Investigational Site
city: München
country: Germany
facility: 1199.34.49006 Boehringer Ingelheim Investigational Site
city: Münster
country: Germany
facility: 1199.34.49004 Boehringer Ingelheim Investigational Site
city: Athens
country: Greece
facility: 1199.34.30005 Boehringer Ingelheim Investigational Site
city: Heraklion
country: Greece
facility: 1199.34.30001 Boehringer Ingelheim Investigational Site
city: Larisa
country: Greece
facility: 1199.34.30004 Boehringer Ingelheim Investigational Site
city: Maroussi, Athens
country: Greece
facility: 1199.34.30002 Boehringer Ingelheim Investigational Site
city: Nikaia
country: Greece
facility: 1199.34.30003 Boehringer Ingelheim Investigational Site
city: Ahmedabad
country: India
facility: 1199.34.91051 Boehringer Ingelheim Investigational Site
city: Banglore
country: India
facility: 1199.34.91053 Boehringer Ingelheim Investigational Site
city: Jaipur
country: India
facility: 1199.34.91056 Boehringer Ingelheim Investigational Site
city: Pune
country: India
facility: 1199.34.91054 Boehringer Ingelheim Investigational Site
city: Pune
country: India
facility: 1199.34.91055 Boehringer Ingelheim Investigational Site
city: Himeji, Hyogo
country: Japan
facility: 1199.34.81059 Boehringer Ingelheim Investigational Site
city: Kawasaki, Kanagawa
country: Japan
facility: 1199.34.81063 Boehringer Ingelheim Investigational Site
city: Kobe, Hyogo
country: Japan
facility: 1199.34.81060 Boehringer Ingelheim Investigational Site
city: Minato-ku, Tokyo
country: Japan
facility: 1199.34.81051 Boehringer Ingelheim Investigational Site
city: Nagoya, Aichi
country: Japan
facility: 1199.34.81054 Boehringer Ingelheim Investigational Site
city: Ogaki, Gifu
country: Japan
facility: 1199.34.81055 Boehringer Ingelheim Investigational Site
city: Osaka-Sayama, Osaka
country: Japan
facility: 1199.34.81058 Boehringer Ingelheim Investigational Site
city: Sakai, Osaka
country: Japan
facility: 1199.34.81057 Boehringer Ingelheim Investigational Site
city: Seto, Aichi
country: Japan
facility: 1199.34.81053 Boehringer Ingelheim Investigational Site
city: Shinjuku-ku, Tokyo
country: Japan
facility: 1199.34.81052 Boehringer Ingelheim Investigational Site
city: Tenri, Nara
country: Japan
facility: 1199.34.81056 Boehringer Ingelheim Investigational Site
city: Tokushima, Tokushima
country: Japan
facility: 1199.34.81062 Boehringer Ingelheim Investigational Site
city: Yonago, Tottori
country: Japan
facility: 1199.34.81061 Boehringer Ingelheim Investigational Site
city: Bucheon
country: Korea, Republic of
facility: 1199.34.82002 Boehringer Ingelheim Investigational Site
city: Incheon
country: Korea, Republic of
facility: 1199.34.82004 Boehringer Ingelheim Investigational Site
city: Seoul
country: Korea, Republic of
facility: 1199.34.82001 Boehringer Ingelheim Investigational Site
city: Seoul
country: Korea, Republic of
facility: 1199.34.82003 Boehringer Ingelheim Investigational Site
city: Seoul
country: Korea, Republic of
facility: 1199.34.82006 Boehringer Ingelheim Investigational Site
city: Seoul
country: Korea, Republic of
facility: 1199.34.82007 Boehringer Ingelheim Investigational Site
city: Mexico DF
country: Mexico
facility: 1199.34.52001 Boehringer Ingelheim Investigational Site
city: Amsterdam
country: Netherlands
facility: 1199.34.31002 Boehringer Ingelheim Investigational Site
city: Nieuwegein
country: Netherlands
facility: 1199.34.31001 Boehringer Ingelheim Investigational Site
city: Rotterdam
country: Netherlands
facility: 1199.34.31003 Boehringer Ingelheim Investigational Site
city: Amadora
country: Portugal
facility: 1199.34.35107 Boehringer Ingelheim Investigational Site
city: Coimbra
country: Portugal
facility: 1199.34.35105 Boehringer Ingelheim Investigational Site
city: Lisboa
country: Portugal
facility: 1199.34.35102 Boehringer Ingelheim Investigational Site
city: Lisboa
country: Portugal
facility: 1199.34.35103 Boehringer Ingelheim Investigational Site
city: Porto
country: Portugal
facility: 1199.34.35101 Boehringer Ingelheim Investigational Site
city: Vila Nova de Gaia
country: Portugal
facility: 1199.34.35106 Boehringer Ingelheim Investigational Site
city: Kazan
country: Russian Federation
facility: 1199.34.07001 Boehringer Ingelheim Investigational Site
city: St. Petersburg
country: Russian Federation
facility: 1199.34.07003 Boehringer Ingelheim Investigational Site
city: Barcelona
country: Spain
facility: 1199.34.34001 Boehringer Ingelheim Investigational Site
city: Barcelona
country: Spain
facility: 1199.34.34003 Boehringer Ingelheim Investigational Site
city: Barcelona
country: Spain
facility: 1199.34.34004 Boehringer Ingelheim Investigational Site
city: Hospitalet de Llobregat
country: Spain
facility: 1199.34.34005 Boehringer Ingelheim Investigational Site
city: Madrid
country: Spain
facility: 1199.34.34009 Boehringer Ingelheim Investigational Site
city: Sevilla
country: Spain
facility: 1199.34.34008 Boehringer Ingelheim Investigational Site
city: Ankara
country: Turkey
facility: 1199.34.90003 Boehringer Ingelheim Investigational Site
city: Istanbul
country: Turkey
facility: 1199.34.90001 Boehringer Ingelheim Investigational Site
city: Istanbul
country: Turkey
facility: 1199.34.90005 Boehringer Ingelheim Investigational Site
city: Izmir
country: Turkey
facility: 1199.34.90002 Boehringer Ingelheim Investigational Site
city: Izmir
country: Turkey
facility: 1199.34.90004 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
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