PT  - JOURNAL ARTICLE
AU  - Gerald Smaldone
AU  - Jie Yang
AU  - Rany Condos
TI  - Treatment of IPF with inhaled IFN-γ; planning for a clinical trial
DP  - 2014 Sep 01
TA  - European Respiratory Journal
PG  - P775
VI  - 44
IP  - Suppl 58
4099  - http://erj.ersjournals.com/content/44/Suppl_58/P775.short
4100  - http://erj.ersjournals.com/content/44/Suppl_58/P775.full
SO  - Eur Respir J2014 Sep 01; 44
AB  - Objectives:In a recent safety study we analyzed the effect of inhaled interferon-γ (IFN-γ) on pulmonary function before and after therapy. We tested the power of our data to predict an endpoint for a controlled clinical trial.Methods:Ten patients with IPF received inhaled IFN-γ 100µg 3x/week for 80-130 weeks delivered with I-neb (Philips Respironics). Full PFTs were measured 20-50 weeks before Rx and monthly during Rx. Linear mixed models were used to test the PFT change over time. Autoregressive dependence structure (order one) was the best to model the intra-patient correlation over time. 89 observations were used to build models. PFT with significant changes before and after Rx were used as the primary endpoint to define potential placebo-controlled phase 3 studiesResults:All patients tolerated at least 80 weeks of inhaled IFN-γ well, with no systemic side effects. After initiation of inhaled IFN-γ, there was a marked change in slope of the DLCO curve from negative to positive indicating an improvement in this parameter. The change over time in DLCO was significantly different before and after interferon treatment (p-value=0.03). Changes in TLC, FRC, RV and FVC were not significant.Power calculations were performed for different sample sizes based on 1000 simulation runs for each sample size. For a sample size of 60, a placebo controlled, randomized trial has a 90% power to detect a significant difference in the change rate of DLCO.Conclusions:Inhaled IFN-γ is safe with no systemic side effects in IPF over many months of therapy. DLCO appears to be a sensitive index of response to inhaled IFN-γ. As a result of this response, a relatively small sample size for a placebo-controlled trial is possible.