Clinical trial NCT01335464: Safety and Efficacy of BIBF 1120 at High Dose in Idiopathic Pulmonary Fibrosis Patients
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: 515
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 of FVC (% Predicted) by Categories Over 52 Weeks - 5% Threshold
timeFrame: Baseline and 52 weeks
measure: Absolute Categorical Change 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: 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 Symptoms 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: Birmingham
country: United States
facility: 1199.32.10007 Boehringer Ingelheim Investigational Site
state: Alabama
city: Jasper
country: United States
facility: 1199.32.10029 Boehringer Ingelheim Investigational Site
state: Alabama
city: Phoenix
country: United States
facility: 1199.32.10013 Boehringer Ingelheim Investigational Site
state: Arizona
city: Los Angeles
country: United States
facility: 1199.32.10005 Boehringer Ingelheim Investigational Site
state: California
city: Danbury
country: United States
facility: 1199.32.10022 Boehringer Ingelheim Investigational Site
state: Connecticut
city: Newark
country: United States
facility: 1199.32.10025 Boehringer Ingelheim Investigational Site
state: Delaware
city: Weston
country: United States
facility: 1199.32.10023 Boehringer Ingelheim Investigational Site
state: Florida
city: Council Bluffs
country: United States
facility: 1199.32.10001 Boehringer Ingelheim Investigational Site
state: Iowa
city: Wichita
country: United States
facility: 1199.32.10028 Boehringer Ingelheim Investigational Site
state: Kansas
city: Minneapolis
country: United States
facility: 1199.32.10016 Boehringer Ingelheim Investigational Site
state: Minnesota
city: New Brunswich
country: United States
facility: 1199.32.10024 Boehringer Ingelheim Investigational Site
state: New Jersey
city: New York
country: United States
facility: 1199.32.10019 Boehringer Ingelheim Investigational Site
state: New York
city: Cincinnati
country: United States
facility: 1199.32.10004 Boehringer Ingelheim Investigational Site
state: Ohio
city: Portland
country: United States
facility: 1199.32.10020 Boehringer Ingelheim Investigational Site
state: Oregon
city: Pittsburgh
country: United States
facility: 1199.32.10002 Boehringer Ingelheim Investigational Site
state: Pennsylvania
city: Pittsburgh
country: United States
facility: 1199.32.10033 Boehringer Ingelheim Investigational Site
state: Pennsylvania
city: Providence
country: United States
facility: 1199.32.10008 Boehringer Ingelheim Investigational Site
state: Rhode Island
city: Nashville
country: United States
facility: 1199.32.10015 Boehringer Ingelheim Investigational Site
state: Tennessee
city: Shelbyville
country: United States
facility: 1199.32.10034 Boehringer Ingelheim Investigational Site
state: Tennessee
city: Dallas
country: United States
facility: 1199.32.10009 Boehringer Ingelheim Investigational Site
state: Texas
city: McKinney
country: United States
facility: 1199.32.10018 Boehringer Ingelheim Investigational Site
state: Texas
city: Falls Church
country: United States
facility: 1199.32.10021 Boehringer Ingelheim Investigational Site
state: Virginia
city: Lynchburg
country: United States
facility: 1199.32.10003 Boehringer Ingelheim Investigational Site
state: Virginia
city: Tacoma
country: United States
facility: 1199.32.10038 Boehringer Ingelheim Investigational Site
state: Washington
city: Camperdown
country: Australia
facility: 1199.32.61001 Boehringer Ingelheim Investigational Site
state: New South Wales
city: Concord
country: Australia
facility: 1199.32.61002 Boehringer Ingelheim Investigational Site
state: New South Wales
city: Daw Park
country: Australia
facility: 1199.32.61003 Boehringer Ingelheim Investigational Site
state: South Australia
city: Frankston
country: Australia
facility: 1199.32.61005 Boehringer Ingelheim Investigational Site
state: Victoria
city: Prahran
country: Australia
facility: 1199.32.61004 Boehringer Ingelheim Investigational Site
state: Victoria
city: Bruxelles
country: Belgium
facility: 1199.32.32004 Boehringer Ingelheim Investigational Site
city: Jette
country: Belgium
facility: 1199.32.32005 Boehringer Ingelheim Investigational Site
city: Leuven
country: Belgium
facility: 1199.32.32001 Boehringer Ingelheim Investigational Site
city: Yvoir
country: Belgium
facility: 1199.32.32002 Boehringer Ingelheim Investigational Site
city: Beijing
country: China
facility: 1199.32.86001 Boehringer Ingelheim Investigational Site
city: Beijing
country: China
facility: 1199.32.86002 Boehringer Ingelheim Investigational Site
city: Changsha
country: China
facility: 1199.32.86005 Boehringer Ingelheim Investigational Site
city: Chengdu
country: China
facility: 1199.32.86004 Boehringer Ingelheim Investigational Site
city: Nanchang
country: China
facility: 1199.32.86003 Boehringer Ingelheim Investigational Site
city: Xi'An
country: China
facility: 1199.32.86006 Boehringer Ingelheim Investigational Site
city: Prague 4
country: Czech Republic
facility: 1199.32.42003 Boehringer Ingelheim Investigational Site
city: Prague 8
country: Czech Republic
facility: 1199.32.42002 Boehringer Ingelheim Investigational Site
city: Usti nad Labem
country: Czech Republic
facility: 1199.32.42001 Boehringer Ingelheim Investigational Site
city: Bobigny
country: France
facility: 1199.32.33002 Boehringer Ingelheim Investigational Site
city: Nice Cedex 1
country: France
facility: 1199.32.33003 Boehringer Ingelheim Investigational Site
city: Paris Cedex 15
country: France
facility: 1199.32.33006 Boehringer Ingelheim Investigational Site
city: Paris Cedex 18
country: France
facility: 1199.32.33001 Boehringer Ingelheim Investigational Site
city: Paris cedex 20
country: France
facility: 1199.32.33005 Boehringer Ingelheim Investigational Site
city: Reims cedex
country: France
facility: 1199.32.33007 Boehringer Ingelheim Investigational Site
city: Rennes Cedex 9
country: France
facility: 1199.32.33004 Boehringer Ingelheim Investigational Site
city: Bamberg
country: Germany
facility: 1199.32.49008 Boehringer Ingelheim Investigational Site
city: Donaustauf
country: Germany
facility: 1199.32.49005 Boehringer Ingelheim Investigational Site
city: Essen
country: Germany
facility: 1199.32.49001 Boehringer Ingelheim Investigational Site
city: Freiburg/Breisgau
country: Germany
facility: 1199.32.49002 Boehringer Ingelheim Investigational Site
city: Gießen
country: Germany
facility: 1199.32.49006 Boehringer Ingelheim Investigational Site
city: Großhansdorf
country: Germany
facility: 1199.32.49003 Boehringer Ingelheim Investigational Site
city: Heidelberg
country: Germany
facility: 1199.32.49007 Boehringer Ingelheim Investigational Site
city: Mainz
country: Germany
facility: 1199.32.49004 Boehringer Ingelheim Investigational Site
city: Ahmedabad
country: India
facility: 1199.32.91003 Boehringer Ingelheim Investigational Site
city: Coimbatore
country: India
facility: 1199.32.91002 Boehringer Ingelheim Investigational Site
city: Jaipur
country: India
facility: 1199.32.91006 Boehringer Ingelheim Investigational Site
city: Kolkatta
country: India
facility: 1199.32.91005 Boehringer Ingelheim Investigational Site
city: Mumbai
country: India
facility: 1199.32.91001 Boehringer Ingelheim Investigational Site
city: Dublin
country: Ireland
facility: 1199.32.35301 Boehringer Ingelheim Investigational Site
city: Haifa
country: Israel
facility: 1199.32.97004 Boehringer Ingelheim Investigational Site
city: Petah Tiqwa
country: Israel
facility: 1199.32.97001 Boehringer Ingelheim Investigational Site
city: Rehovot
country: Israel
facility: 1199.32.97002 Boehringer Ingelheim Investigational Site
city: Catania
country: Italy
facility: 1199.32.39012 Boehringer Ingelheim Investigational Site
city: Chieti Scalo
country: Italy
facility: 1199.32.39004 Boehringer Ingelheim Investigational Site
city: Forli'
country: Italy
facility: 1199.32.39008 Boehringer Ingelheim Investigational Site
city: Milano
country: Italy
facility: 1199.32.39005 Boehringer Ingelheim Investigational Site
city: Modena
country: Italy
facility: 1199.32.39001 Boehringer Ingelheim Investigational Site
city: Monza
country: Italy
facility: 1199.32.39007 Boehringer Ingelheim Investigational Site
city: Napoli
country: Italy
facility: 1199.32.39011 Boehringer Ingelheim Investigational Site
city: Padova
country: Italy
facility: 1199.32.39002 Boehringer Ingelheim Investigational Site
city: Pisa
country: Italy
facility: 1199.32.39006A Boehringer Ingelheim Investigational Site
city: Pisa
country: Italy
facility: 1199.32.39006B Boehringer Ingelheim Investigational Site
city: Roma
country: Italy
facility: 1199.32.39010 Boehringer Ingelheim Investigational Site
city: Siena
country: Italy
facility: 1199.32.39009 Boehringer Ingelheim Investigational Site
city: Bunkyo-ku,Tokyo
country: Japan
facility: 1199.32.81005 Boehringer Ingelheim Investigational Site
city: Bunkyo-ku,Tokyo
country: Japan
facility: 1199.32.81006 Boehringer Ingelheim Investigational Site
city: Kiyose, Tokyo
country: Japan
facility: 1199.32.81007 Boehringer Ingelheim Investigational Site
city: Kumagaya, Saitama
country: Japan
facility: 1199.32.81004 Boehringer Ingelheim Investigational Site
city: Minato-ku, Tokyo
country: Japan
facility: 1199.32.81009 Boehringer Ingelheim Investigational Site
city: Naka-gun, Ibaraki
country: Japan
facility: 1199.32.81003 Boehringer Ingelheim Investigational Site
city: Ota-ku, Tokyo
country: Japan
facility: 1199.32.81011 Boehringer Ingelheim Investigational Site
city: Sendai, Miyagi
country: Japan
facility: 1199.32.81001 Boehringer Ingelheim Investigational Site
city: Shibuya-ku, Tokyo
country: Japan
facility: 1199.32.81010 Boehringer Ingelheim Investigational Site
city: Shimotsuke,Tochigi
country: Japan
facility: 1199.32.81002 Boehringer Ingelheim Investigational Site
city: Shinjuku-ku, Tokyo
country: Japan
facility: 1199.32.81008 Boehringer Ingelheim Investigational Site
city: Yokohama, Kanagawa
country: Japan
facility: 1199.32.81012 Boehringer Ingelheim Investigational Site
city: Aberdeen
country: United Kingdom
facility: 1199.32.44006 Boehringer Ingelheim Investigational Site
city: Birmingham
country: United Kingdom
facility: 1199.32.44003 Boehringer Ingelheim Investigational Site
city: Birmingham
country: United Kingdom
facility: 1199.32.44005 Boehringer Ingelheim Investigational Site
city: Leeds
country: United Kingdom
facility: 1199.32.44009 Boehringer Ingelheim Investigational Site
city: Liverpool
country: United Kingdom
facility: 1199.32.44004 Boehringer Ingelheim Investigational Site
city: London
country: United Kingdom
facility: 1199.32.44002 Boehringer Ingelheim Investigational Site
city: Oxford
country: United Kingdom
facility: 1199.32.44008 Boehringer Ingelheim Investigational Site
city: Westbury on Trym
country: United Kingdom
facility: 1199.32.44001 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Glaspole I, Bonella F, Bargagli E, Glassberg MK, Caro F, Stansen W, Quaresma M, Orsatti L, Bendstrup E. Efficacy and safety of nintedanib in patients with idiopathic pulmonary fibrosis who are elderly or have comorbidities. Respir Res. 2021 Apr 26;22(1):125. doi: 10.1186/s12931-021-01695-y.
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citation: Rinciog C, Watkins M, Chang S, Maher TM, LeReun C, Esser D, Diamantopoulos A. A Cost-Effectiveness Analysis of Nintedanib in Idiopathic Pulmonary Fibrosis in the UK. Pharmacoeconomics. 2017 Apr;35(4):479-491. doi: 10.1007/s40273-016-0480-2.
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