Infinitix-BOS Trial: Multi-Center, Randomised, Double-Blind Placebo-Controlled Trial of Nintedanib in Lung Transplant Recipients with Bronchiolitis Obliterans Syndrome (BOS) Grade 0-p and Grade 1-2.

Lung transplantation (TxP) is now a validated treatment of end-stage pulmonary diseases, but long-term survival are still hampered by the development of chronic allograft dysfunction (CLAD) affecting> 50% of patients. Bronchiolitis obliterans syndrome/obliterative bronchiolitis (BOS/OB) is the most common manifestation of CLAD. Survival after onset of BOS is poor (<50% at 3 years). OB is thought to arise from repeated injury to graft epithelial cells, leading to fibrous scarring and obliteration of the small airway lumen. The crucial role of a dysregulated fibrotic repair demonstrated in BOS strongly suggests the potential role of tyrosine kinase inhibitors (TKI) that target these growth factors involved in OB. The TKI Nintedanib, demonstrated as effective in the treatment of idiopathic pulmonary fibrosis (IPF) appears as a candidate molecule. Hence, we started a Nintedanib trial in LTx recipients with BOS because of : (i) High unmet medical need in BOS; (ii) fibrotic pathway involved in BOS; (iii) efficacy of nintedanib in IPF. A phase III clinical randomized trial to assess the efficacy of Nintedanib in LTx recipients with BOS. Inclusion criteria: n=80 LTx recipients with BOS 0p-1-2, with a decline of FEV1> 200ml within the previous year. Primary Objective : to assess Nintedanib efficacy in the reduction of the rate of decline of FEV1 (forced expiratory volume in 1 sec) at a dose of 150 mg twice daily (bid) compared to placebo over 6 months. Secondary Objectives : to assess Nintedanib efficacy and tolerance in the treatment of BOS 0p-1-2, based on the change over 6 months of : 6WT, QOL, BOS grade/graft failure, O2 saturation, KL-6, SPD, VEGF, PDGF parameters, and tolerance. The trial was started in December 2019 among 8 french LTx centers (Hôpital Foch, Bichat, HEGP/Cochin, Marie-Lannelongue, Marseille, Bordeaux, Strasbourg, and Grenoble), for a total duration of inclusion anticipated at 36 months. On October 15th 2020, 14 patients were already included. Infinitix-BOS is the first therapeutic randomized trial testing the efficacy of nintedanib in LTx recipients with BOS. In case of demonstrated effectiveness of Nintedanib, the benefit for LTx patients with BOS seems high in terms of stabilization of lung function and enhancement of survival. [ABSTRACT FROM AUTHOR]