Management of Progressive Disease in Idiopathic Pulmonary Fibrosis

Inclusion Criteria:

• Patient aged ≥ 50 years.

• Patient with Idiopathic Pulmonary Fibrosis satisfying the ATS/ERS/JRS/ALATdiagnostic criteria (29) diagnosed.

In the absence of a surgical lung biopsy, high-resolution computed tomography (HRCT) must be "consistent with Usual Interstitial Pneumonia (UIP)" defined as meeting either criteria A, B, and C, or criteria A and C, or criteria B and C below:

A. Definite honeycomb lung destruction with basal and peripheral predominance. B. Presence of reticular abnormality and traction bronchiectasis consistent with fibrosis, with basal and peripheral predominance.

C. Atypical features are absent, specifically nodules and consolidation. Ground glass opacity, if present, is less extensive than reticular opacity pattern.

• Patient who fulfill at least 1 of the 4 criteria for IPF progression in the 12months (+/- one six months) before screening, despite antifibrotic treatment inclinical practice (if yes check the option(s)). These criteria are: 0 Relativedecline in FVC ≥10% predicted 0 Relative decline in FVC ≥5-<10% predicted andworsened respiratory symptoms 0 Relative decline in FVC ≥5-<10% predicted andincreased extent of fibrotic changes on chest imaging 0 Worsened respiratorysymptoms and increased extent of fibrotic changes on chest imaging

• Patient must have been on a stable dose of pirfenidone or nintedanib prescribed asfirst-line therapy for at least 6 months, with good tolerance of 1602 to 2403 mg perday of pirfenidone or 200 to 300 mg per day of nintedanib.

• Patient who has a FVC ≥ 45% of predicted.

• Patient who has a forced expiratory volume in 1 second (FEV1)/FVC ratio > 0.70.

• Patient who has a life expectancy of at least 9 months.

• Patient who has provided his written informed consent to participate in the study.

• Patient affiliated to a social insurance regimen.

Exclusion Criteria:

• Patients under judicial protection.

• Female patient who is pregnant or lactating, or is of child bearing potential (defined as a sexually mature woman not surgically sterilized or not post-menopausalfor at least 24 consecutive months if ≤ 55 years or 12 months if > 55 years) and whodid not agree to use highly effective methods of birth control throughout the study.

• Patient who is currently on both pirfenidone and nintedanib.

• Patient who has already received pirfenidone and nintedanib either concomitantly orsuccessively.

• Patient who has a contra-indication to pirfenidone or nintedanib.

• Patient who has emphysema > 15% on HRCT or the extent of emphysema is greater thanthe extent of fibrosis according to reported results from the most recent HRCT.

• Patient who had acute exacerbation of idiopathic pulmonary fibrosis within theprevious 3 months.

• Patient who has a history of cigarette smoking within the previous 3 months.

• Patient who has received experimental therapy for IPF within 4 weeks beforebaseline.

• Patient who is receiving systemic corticosteroids equivalent to prednisone > 15mg/day or equivalent within 2 weeks before baseline.

• Patient who received Immuno-suppressants (e.g. methotrexate, azathioprine,cyclophosphamide, cyclosporine, sirolimus, everolimus or other immunosuppressants)within 4 weeks before baseline.

• Patient who has a history of a malignancy within the previous 5 years, with theexception of basal cell skin neoplasms. In addition, a malignant diagnosis orcondition first occurring prior to 5 years must be considered cured, inactive, andnot under current treatment.

• Patient who, in the Investigator's opinion, is not able to perform home spirometryin accordance with the protocol.

• Patient who has any concurrent condition other than IPF that, in the Investigator'sopinion, is unstable and/or would impact the likelihood of survival for the studyduration or the subject's ability to complete the study as designed, or mayinfluence any of the safety or efficacy assessments included in the study.

• Patient who has baseline resting oxygen saturation of < 88% on room air orsupplemental oxygen.

• Patient who had lung transplantation or who is on a lung transplant list and theinvestigator anticipates the patient will not be able to complete the study prior totransplant.