Pilot Study of Pirfenidone in Pulmonary Fibrosis With Anti-myeloperoxydase Antibodies
Pilot Study of Pirfenidone in Pulmonary Fibrosis With Anti-myeloperoxydase Antibodies
The purpose of this study is to determine wether pirfenidone is safe and effective in the
 treatment of pulmonary fibrosis with anti-myeloperoxydase (MPO) antibodies or pulmonary
 fibrosis with anti-MPO associated vasculitis.
Pulmonary fibrosis can be associated with Anti-Neutrophil Cytoplasmic Antibody (ANCA)
 directed against MPO or with anti-MPO associated vasculitis, leading to increased disability
 and poor prognosis. The pathophysiology of this association remains unclear. Conventional
 therapies used for the treatment of vasculitis manifestations are often disappointing for the
 treatment of pulmonary fibrosis. The main cause of death in patients with anti-MPO ANCA
 associated vasculitis and associated pulmonary fibrosis is the progression of pulmonary
 fibrosis. No treatment has demonstrated efficacy to stabilize or improve pulmonary fibrosis
 associated with anti-MPO associated vasculitis.

 Previous studies showed that Pirfenidone improves survival and pulmonary function in patients
 with idiopathic pulmonary fibrosis (IPF) and that Pirfenidone treatment is safe and well
 tolerated in IPF. Patients with anti-MPO associated vasculitis (or anti-MPO antibodies
 without vasculitis) and associated pulmonary fibrosis might benefit from the use of
 Pirfenidone. However, the efficacy and safety of pirfenidone in patients with anti-MPO
 associated vasculitis and associated pulmonary fibrosis has not been evaluated. This study
 was designed to assess the efficacy and safety of pirfenidone in patients with pulmonary
 fibrosis and anti-MPO ANCA associated vasculitis or anti-MPO antibodies without vasculitis.
Inclusion Criteria:

 -  Age > 18 years

 -  Presence of anti-MPO antibody (ELISA) at inclusion or during pulmonary fibrosis
 follow-up and/or diagnosis of anti-MPO associated vasculitis according to the 2012
 Revised International Chapel Hill Consensus Conference definitions

 -  Definite or possible Usual Interstitial Pneumonia or Non Specific Interstitial
 Pneumonia based on high-resolution computed tomography

 -  Presence of pulmonary fibrosis, defined as a range of 50 to 90% of the %FVC and a
 range of 30 to 90% of the %DLCO

 -  Pulmonary fibrosis refractory (according to the investigator's judgment) to a
 conventional regimen used for anti-MPO associated vasculitis when a treatment against
 vasculitis has been used

 -  Have the ability to understand the requirements of the study, provide written informed
 consent (including consent for the use and disclosure of research-related health
 information) and comply with the study protocol procedures (including required study
 visits)

 -  Have affiliation with a mode of social security (profit our being entitled).

 Exclusion Criteria:

 -  Other type of systemic vasculitis;

 -  Active vasculitis defined by Birmingham Vasculitis Activity Score >3 (BVAS) ;

 -  Contraindication to Pirfenidone;

 -  Unable to perform pulmonary function test (PFT);

 -  Pregnancy or lactation. Women of childbearing capacity are required to have a negative
 serum pregnancy test before treatment and must agree to maintain highly effective
 contraception by practicing abstinence or by using an effective method of birth
 control from the date of consent through the end of the study : implants of
 levonorgestrel; injectable progesterone; any intrauterine device (IUD) with a
 documented failure rate of less than 1% per year; oral contraceptives (either combined
 or progesterone only); double barrier method (condom, cervical cap or diaphragm with
 spermicidal agent); transdermal contraceptive patch; male partner who is sterile prior
 to the female subject's entry into the study and is the sole sexual partner for the
 female subject;

 -  Any of the following liver function test criteria above specified limits: total
 bilirubin above 1,5 times the upper limit of normal (ULN), excluding patients with
 Gilbert's syndrome; aspartate (AST)/Glutamate Oxaloacétique Transaminase (SGOT) or
 alanine aminotransferase (ALT)/Glutamate Pyruvate Transaminase (SGPT), (AST/SGOT or
 ALT/SGPT) >3 × ULN; alkaline phosphatase >2.5 × ULN;

 -  Creatinine clearance (CrCl<30) mL/min, calculated using the Cockcroft-Gault formula at
 screening

 -  Current treatment with Nintedanib or past treatment with Nintedanib in the last 12
 months;

 -  Current treatment with Fluvoxamine or past treatment with Fluvoxamine in the last 28
 days before screening

 -  Prior use of Pirfenidone or known hypersensitivity to any of the components of study
 treatment;

 -  Expected to receive a lung transplant within 1 year from randomization or, on a lung
 transplant waiting list at randomization;

 -  Associated connective tissue disease (such as systemic sclerosis).;

 -  Electrocardiogram (ECG), with a heart-rate-corrected QT interval (corrected using
 Fridericia's formula, QTcF) ≥ 500 ms at Screening, or a family or personal history of
 long QT syndrome;

 -  Treatment with Cyclophosphamide in the last 3 months;

 -  Current smoking or past smoking in the last 3 months.