Systemic Sclerosis-Related Interstitial Lung Disease
Conditions
Interventions
Trade Name: Esbriet
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: PIRFENIDONE
CAS Number: 53179-13-8
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 267-
Sponsors
InterMune Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Eligible patients are to fulfill the preliminary criteria of the American College of Rheumatology for the classification of SSc (Masi 1980) and have a confirmed diagnosis of SSc-ILD based on pulmonary function testing and radiologic data. Patients who meet all of the following criteria are eligible to participate in the study: Demographic Characteristics: 1. Male and female patients, aged 18-70 years (inclusive) on Day 1 SSc- and SSc-ILD-Related Criteria: 2. Diagnosis of SSc confirmed by the investigator using the preliminary criteria of the American College of Rheumatology for the classification of systemic sclerosis (Masi 1980, Appendix B) a. Duration of diagnosis =65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: 1. Clinically significant pulmonary hypertension, based on any of the following criteria: a. Receiving treatment for pulmonary hypertension b. Or, if available, a previous right heart catheterization that demonstrates mean pulmonary artery pressure at rest of =25 mm Hg with concurrent wedge pressure of =15 mm Hg and pulmonary vascular resistance of >3 Wood units c. Or, Doppler echocardiography in the 6 months before D1 with an estimated systolic pulmonary arterial pressure (Ppa) of >36 mm Hg corresponding to a tricuspid regurgitant jet velocity of >2.8 m/sec 2. Evidence of right atrial or ventricular enlargement or significant left ventricular dysfunction 3. Known underlying liver disease (e.g., hepatitis or cirrhosis) 4. Clinical evidence of significant aspiration or uncontrolled gastroesophageal reflux (UCLA SCTC GIT 2.0 reflux score >1.00), as assessed by the investigator 5. Known achalasia, esophageal stricture, or esophageal dysfunction sufficient to limit the ability to swallow oral medication 6. Tobacco smoking within 3 months of screening or unwillingness to avoid smoking throughout the study 7. History of a clinically significant environmental exposure that is known to cause PF including, but not limited to, drugs (e.g., amiodarone), asbestos, beryllium, radiation, or domestic birds or other factors associated with hypersensitivity pneumonitis 8. History of clinically significant asthma as an adult or clinically significant chronic obstructive pulmonary disease, as assessed by the investigator 9. Clinical evidence of active infection including, but not limited to, bronchitis, pneumonia, sinusitis, or UTI. 10. Features supporting diagnosis of another connective-tissue disorder (e.g., RA or SLE) or another pulmonary disorder (e.g., emphysema, asthma, cancer) 11. Expected to have study participation interrupted for a foreseeable medical or surgical event (e.g., organ, stem cell, or bone marrow transplant). 12. Any clinical evidence of a malignancy that is likely to result in significant disability or likely to require significant medical or surgical intervention within the next 6 months (relative to D1). Excluded: minor surgical procedures for localized cancer (basal cell carcinoma). 13. Any condition (other than SSc-ILD) likely to result in the death of the patient within 12 months, as assessed by the investigator 14. History of unstable or deteriorating cardiac or pulmonary disease (other than SSc-ILD) within the previous 6 months (relative to D1) including, but not limited to unstable angina pectoris, myocardial infarction, congestive heart failure requiring hospitalization, uncontrolled clinically significant arrhythmia, pulmonary hypertension (see Exclusion Criterion 1) 15. Any condition that, as assessed by the investigator, might be significantly exacerbated by the known side effects associated with pirfenidone 16. Known or suspected peptic ulcer 17. Pregnancy or lactation: Positive pregnancy test; currently lactating; or for women of childbearing potential, an unwillingness to maintain highly effective contraception, as described in Inclusion Criterion 8 18. History of alcohol or substance abuse in the previous 2 years (relative to D1) 19. Family or personal history of long QT syndrome 20. Any of the following liver test criteria above the specified limit: a. Total bilirubin above ULN, except in patients with predominantly unconjugated hyperbilirubinemia (Gilbert’s syndrome) b. AST or ALT >2 × ULN
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the safety and tolerability of pirfenidone at 2403 mg/d when administered to patients with systemic sclerosis-related interstitial lung disease (SSc-ILD) ;Secondary Objective: To assess the safety and tolerability of two pirfenidone dose-titration schedules;Primary end point(s): - Evaluation of AEs and SAEs - Study treatment discontinuations - Treatment-emergent changes in clinical laboratory measures - Treatment emergent changes in ECGs - Patient responses on the UCLA SCTC GIT 2.0 questionnaire - Spirometry - DLCO - Disease status scales ;Timepoint(s) of evaluation of this end point: - AE and SAE monitoring through directed medical history: D-21 to 1, D1, D7, D14, D28, D42, D56, D70, D84, D98, D112 and 28-35 d post dosing - Study treatment discontinuations: D7, D14, D28, D42, D56, D70, D84, D98, D112 - Clinical lab measures (hematology, serum chemistry): D-21 to 1, D1, D14, D28, D56, D84, D112 - 12-lead ECG: D-21 to 1, D1, D14, D56, D112 - UCLA SCTC GIT 2.0: D-21 to 1, D1, D28, D56, D84, D112 - Spirometry: D-21 to 1, D112 - DLCO: D-21 to 1, D112 - Disease status scales: D1, D112 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Dose modifications and associated AE and SAEs;Timepoint(s) of evaluation of this end point: - Dose modifications: D7, D14, D28, D42, D56, D70, D84, D98, D112 | — |
Countries
Canada, Italy, United States
Contacts
Public ContactProject Management
Theorem Clinical Research GmbH
Outcome results
None listed