A Phase-2 Exploratory Randomized Controlled Trial of INOpulse in Patients with Fibrotic Interstitial Lung Disease Requiring Oxygen.

RATIONALE Patients with fibrotic interstitial lung disease often progress to the point of requiring supplemental oxygen. This is invariably accompanied by an impaired quality of life and limitations on activities of daily living. OBJECTIVE This study aimed to assess the improvement in physical activity in patients with interstitial lung disease requiring supplemental oxygen treated with pulsed inhaled nitric oxide (iNO) via INOpulse. Additionally, it sought to explore the safety and clinical benefits of INOpulse on multiple patient reported outcomes. METHODS Ambulatory fibrotic lung disease patients on supplemental oxygen were randomized in a 2:1 ratio to iNO at 45 µg/kg ideal body weight (IBW)/hr (iNO45) or placebo for four months (3 months post-baseline) of blinded treatment. The study assessed multiple exploratory efficacy endpoints including moderate-to vigorous physical activity (MVPA) as measured by actigraphy and patient reported outcomes using the UCSD Shortness of Breath Questionnaire (UCSD SOBQ) and the St. George's Respiratory Questionnaire (SGRQ). RESULTS 44 patients (30 iNO45, 14 placebo) were enrolled. A placebo-corrected clinical benefit of 12.3-minutes per day increase in MVPA was observed in the iNO45 group. Clinically meaningful beneficial trends were observed for the UCSD SOBQ (6.05 points) and the SGRQ Total (3.75) scores, as well as the SGRQ activity (5.84), and SGRQ Impact (6.30) domains. CONCLUSIONS INOpulse was well tolerated and associated with maintenance of physical activity and improved symptomatology in patients with interstitial lung disease who require supplemental oxygen. Further validation of this beneficial effect warrants further study in a phase 3 trial that is currently underway. Clinical Trial Registration with ClinicalTrials.gov: NCT03267108 Primary Source of Funding: Bellerophon Therapeutics.