1.Fibrotic NSIP., 2.Chronic Hypersensitivity Pneumonitis 3. Lung fibrosis associated with collagen / vascular diseases, 4.Asbestos-induced lung fibrosis MedDRA version: 20.0 Level: LLT Classification code 10022612 Term: Interstitial lung fibrosis System Organ Class: 100000004855 MedDRA version: 20.0 Level: LLT Classification code 10035754 Term: Pneumonitis hypersensitivity System Organ Class: 100000004855 MedDRA version: 20.0 Level: LLT Classification code 10025088 Term: Lung fibrosis System
Conditions
Interventions
Trade Name: Esbriet® (Pirfenidon)
Product Name: Esbriet® (Pirfenidon)
Product Code: PZN 8881655(RochePharma AG)
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: PIRFENIDONE
CAS Number: 53179-1
Sponsors
Justus Liebig Universität Giessen
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Confident diagnosis of progressive, non-IPF lung fibrosis due to ALF, CVDLF, chronic HP or fNSIP: 1. Clinical symptoms consistent with ALF, CVDLF, chronic HP or fNSIP, including the insidious onset of otherwise unexplained dyspnea on exertion prior to diagnosis 2. Diagnosis of either ALF, CVDLF, chronic HP or fNSIP based on diagnostic criteria outlined in Table 1, at least 9 months before randomization 3. Women of childbearing capacity are required to have a negative serum pregnancy test before treatment and must agree to maintain highly effective methods of contraception by practicing abstinence or by using at least two methods of birth control from the date of consent through the end of the study. If abstinence is not practiced, then one of the two methods of birth control should be an oral contraceptive (e.g., oral contraception and a spermicide) Table 1 Diagnostic criteria for ALF, CVDLF, chronic HP and fNSIP (patients need to fulfil all of the listed diagnostic criteria within one of the categories) Asbestos-induced lung fibrosis • Existence of asbestos-specific pleural changes in HRCT (pleural plaques) • Reticular changes in HRCT and restrictive lung function pattern • History of asbestos exposure • Absence of an alternative explanation for fibrotic lung disease • Absence of extensive pleural plaques and/or effusion Lung fibrosis associated with collagen / vascular diseases • Diagnosis of progressive systemic sclerosis (PSS), mixed connective tissue disease (MCTD), rheumatoid arthritis (RA), Sjörgen’s syndrome, polymyositis/dermatomyositis on the basis of extrapulmonary symptoms and corresponding proof of auto-antibodies • Reticular changes in HRCT and restrictive lung function pattern • Absence of an alternative explanation for fibrotic lung disease Chronic Hypersensitivity Pneumonitis • Previous or current respiratory symptoms (dyspnea, coughing) with a temporal or spatial relation to a causative antigen exposure • Proof of precipitating antibody and/or lymphocytic alveolitis (>30%) • HRCT consistent with chronic HP • Restrictive lung function pattern • Absence of an alternative explanation for fibrotic lung disease Fibrotic NSIP • Histological diagnosis of a fibrotic NSIP pattern by open lung biopsy or cryobiopsy • HRCT consistent with fibrotic NSIP • Restrictive lung function pattern • Absence of an alternative explanation for fibrotic lung disease, especially no clinical suspicion of CVD 4. 18 = Age = 80 years Disease Severity and Progression: 5. Progressive disease in absence of a particular treatment (ALF) or despite a previous or concomitant treatment as outlined in protocol chapter 7.11. Progression prior to study entry must be proven by calculating the slope of a set of at least 3 previous FVC measurements within at least 6 months and at maximum 24 months before screening, showing a (eventually extrapolated) FVC decline of at least 5% (abs. pred.) per year 6. Percent predicted FVC =40%, but 83% on = 6L/min of O2 Informed Consent and Protocol Adherence: 9. Able to understand and sign a written informed consent form 10. Able to understand the importance of adherence to study treatment and the study protocol, including the concomitant medication restricti
Exclusion criteria
Exclusion criteria: 1. Not a suitable candidate for enrolment or unlikely to comply with the requirements of this study, in the opinion of the investigator 2. May not survive the study period, in the opinion of the investigator 3. Premature withdrawal from a randomized clinical trial in the previous 2 years for any reason other than Sponsor decision or current participation in a clinical drug trial 4. Obvious additional obstructive lung disease, as evident from a) forced expiratory volume in the first second (FEV1)/FVC ratio 140% of predicted (before administration of bronchodilator) 5. Other explanation for interstitial lung disease, including but not limited to radiation, sarcoidosis, bronchiolitis obliterans organizing pneumonia, human immunodeficiency virus (HIV), viral hepatitis and cancer 6. Clinical evidence of active infection, including but not limited to bronchitis, pneumonia, sinusitis, urinary tract infection, or cellulitis 7. In the clinical opinion of the investigator, the patient is expected to need and be eligible for a lung transplant within 52 weeks after randomization 8. Unable to undergo pulmonary function testing Medical Exclusions: 9. Any history of malignancy likely to result in death or significant disability or likely to require significant medical or surgical intervention within the next 2 years. This does not include minor surgical procedures for localized carcinoma (e.g. basal cell carcinoma) 10. Any condition other than lung fibrosis which, in the opinion of the investigator, is likely to result in the death of the patient within the next 2 years 11. History of advanced cirrhosis or clinically significant liver disease 12. History of unstable or deteriorating cardiac or pulmonary disease (other than IPF) within the previous 6 months, including but not limited to the following: • Myocardial infarction, unstable angina pectoris, coronary artery bypass surgery, or coronary angioplasty • Congestive heart failure requiring hospitalization • Uncontrolled arrhythmias • Asthma or chronic bronchitis requiring hospitalization in the last 6 months 13. Any condition, which, in the opinion of the investigator, might be significantly exacerbated by the known side effects associated with the administration of pirfenidone 14. Poorly controlled diabetes (defined by glycosylated hemoglobin [HbA1C] >10 %) 15. Pregnancy or lactation 16. History of alcohol or substance abuse in the past 2 years 17. History of any condition or habit associated with altered consciousness and a risk of aspiration in the past 2 years 18. Family or personal history of long QT Syndrome 19. Treatment with either one of the following medications: fluvoxamine (any time), any investigational drug; Stable treatment with PH-specific medication for less than 12 weeks. For individual cases, exemptions can be made after consultation with the Coordination Investigator (LKP) and/or the deputy Coordinating Investigator. 20. Severe pulmonary hypertension with PVR values > 900 dyn 21. Smoking Laboratory Exclusions: 22. Any of the following liver function test criteria above specified limits: total bilirubin >2.5 upper limit of normal (ULN); aspartate or alanine aminotransferase (AST/SGOT or ALT/S
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective will be to investigate the treatment effect on the absolute change in percent predicted FVC from baseline to week 48 in the pirfenidone and placebo group. ;Secondary Objective: Secondary objectives include time to worsening, progression-free survival as well as selected measures of pulmonary function, quality of life questionnaires and safety parameters. ;Primary end point(s): Primary efficacy endpoint: The absolute change in percent predicted FVC from baseline to week 48 in the pirfenidone and placebo group. ;Timepoint(s) of evaluation of this end point: from visit 1 to week 48 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key secondary endpoints: Time to disease worsening, progression-free survival as well as selected measures of pulmonary function, quality of life questionnaires and safety parameters. ;Timepoint(s) of evaluation of this end point: from visit 1 to week 48 | — |
Countries
Germany
Contacts
Public ContactKKS-Marburg
Koordinierungszentrum für Klinische Studien der Philipps-Universität Marburg
Outcome results
None listed