Phase 3
N=551
Safety and Efficacy of BIBF 1120 at High Dose in Idiopathic Pulmonary Fibrosis Patients II
Pulmonary Fibrosis
Bottom Line
View on ClinicalTrials.gov: NCT01335477 ↗Enrolled (actual)
551
Serious AEs
31.0%
Results posted
Feb 2015
Primary outcome: Primary: Annual Rate of Decline in Forced Vital Capacity (FVC) Over 52 Weeks. — -207.32; -113.59 mL/year — p=0.0002
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- placebo (Drug); BIBF 1120 (Drug)
- Age
- Adult, Older Adult · 40+ yrs
- Sex
- All
- Sponsor
- Boehringer Ingelheim
- Primary completion
- Oct 2013
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Annual Rate of Decline in Forced Vital Capacity (FVC) Over 52 Weeks. |
-207.32; -113.59 | 0.0002 sig |
| SECONDARY Change From Baseline in Saint George's Respiratory Questionnaire (SGRQ) Total Score at 52 Weeks |
5.48; 2.80 | 0.0197 sig |
| SECONDARY Time to First Acute Idiopathic Pulmonary Fibrosis (IPF) Exacerbation |
9.6; 3.6; 90.4; 96.4 | 0.0050 sig |
| SECONDARY Absolute Change From Baseline in Forced Vital Capacity (FVC) Over 52 Weeks |
-205.03; -95.26 | <0.0001 sig |
| SECONDARY Relative Change From Baseline in Forced Vital Capacity (FVC) Over 52 Weeks |
-8.14; -3.90 | <0.0001 sig |
| SECONDARY Absolute Change From Baseline in Forced Vital Capacity (FVC) (% Predicted) Over 52 Weeks |
-6.15; -3.09 | <0.0001 sig |
| SECONDARY Relative Change From Baseline in Forced Vital Capacity (FVC) (% Predicted) Over 52 Weeks |
-8.13; -3.92 | <0.0001 sig |
| SECONDARY Absolute Categorical Change From Baseline of FVC (% Predicted) by Categories Over 52 Weeks - 5% Threshold |
52.2; 34.9; 45.0; 50.2; 2.8; 14.9 | — |
| SECONDARY Absolute Categorical Change From Baseline of FVC (% Predicted) by Categories Over 52 Weeks - 10% Threshold |
22.2; 14.9; 77.2; 80.7; 0.6; 4.5 | — |
| SECONDARY FVC Responders Using 10% Threshold at 52 Weeks |
63.93; 69.60 | 0.1833 |
| SECONDARY Proportion of FVC Responders Using 5% Threshold at 52 Weeks |
39.27; 53.19 | 0.0011 sig |
| SECONDARY Proportion of SGRQ Responders at 52 Weeks: Patient Reported Outcomes (PROs) |
16.89; 25.23 | 0.0218 sig |
| SECONDARY Change From Baseline in SGRQ Symptom Score at 52 Weeks (Points): Patient Reported Outcomes (PROs) |
3.43; 2.03 | 0.4019 |
| SECONDARY Change From Baseline in SGRQ Impact Score at 52 Weeks (Points): Patient Reported Outcomes (PROs) |
5.93; 2.85 | 0.0220 sig |
| SECONDARY Change From Baseline in SGRQ Activity Score at 52 Weeks (Points): Patient Reported Outcomes (PROs) |
7.20; 3.89 | 0.0152 sig |
| 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) |
5.84; 2.72 | 0.0089 sig |
| SECONDARY Change From Baseline in Shortness of Breath Questionnaire (SOBQ) at 52 Weeks: Patient Reported Outcomes (PROs) |
9.07; 6.69 | 0.1587 |
| 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) |
-2.38; -0.33 | 0.2326 |
| 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) |
-4.39; -2.58 | 0.2475 |
| SECONDARY Proportion of Patient's Global Impression of Change (PGI-C) Responders at 52 Weeks: Patient Reported Outcomes (PROs) |
53.88; 61.70 | 0.0690 |
| SECONDARY Change From Baseline in EuroQol 5-Dimensional Quality of Life Questionnaire (EQ-5D) Health State up to 52 Weeks : Patient Reported Outcomes (PROs) |
-1.48; -0.57; -4.86; -1.10; -5.60; -2.52 | — |
| SECONDARY Risk of an Acute IPF Exacerbation Over 52 Weeks |
10.2; 3.9 | 0.0070 sig |
| SECONDARY Time to Death Over 52 Weeks |
9.1; 6.7; 90.9; 93.3 | 0.2995 |
| SECONDARY Time to Death Due to Respiratory Cause Over 52 Weeks (Adjudicated) |
5.0; 4.3; 95.0; 95.7 | 0.6654 |
| SECONDARY Time to On-treatment Death |
7.8; 4.9; 92.2; 95.1 | 0.2209 |
| SECONDARY Time to Death or Lung Transplant Over 52 Weeks |
10.0; 6.7; 90.0; 93.3 | 0.1664 |
| SECONDARY Time to Death or Lung Transplant or Qualifying for Lung Transplant Over 52 Weeks. |
23.7; 19.5; 76.3; 80.5 | 0.2123 |
| SECONDARY Change From Baseline in SpO2 (Oxygen Saturation, Expressed in Percent) at Rest up Over 52 Weeks |
-0.66; -0.39 | 0.2032 |
| SECONDARY Change From Baseline in Carbon Monoxide Diffusion Capacity (DLCO) at Rest Over 52 Weeks |
-0.400; -0.286 | 0.2600 |
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
- Age >= 40 years;
- 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;
- 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
- Dlco (corrected for Hb): 30%-79% predicted of normal; 5.FVC>= 50% predicted of normal
Exclusion criteria
- Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) > 1.5 x Upper Limit of Normal (ULN)
- Bilirubin > 1.5 x ULN;
- Relevant airways obstruction (i.e. pre-bronchodilator FEV1/FVC 2, prolongation of prothrombin time (PT) and partial thromboplastin time (PTT) by > 50% of institutional ULN);
- N-ACetyl Cystein, prednisone > 15mg/day or equivalent received within 2 weeks of visit 1;
- Pirfenidone, azathioprine, cyclophosphamide, cyclosporine A received within 8 weeks of visit 1;
Data sourced from ClinicalTrials.gov (NCT01335477). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.