Bovhyaluronidase azoximer for long-term pulmonary sequelae of COVID-19: a randomized, double-blind, placebo-controlled trial

BackgroundHyaluronan is an emerging target for COVID-19 and lung fibrosis. In an open-label study the hyaluronidase bovhyaluronidase azoximer (BA) was associated with improved pulmonary function and exercise tolerance in patients with pulmonary sequelae of COVID-19. In this randomized, double-blind, placebo-controlled trial we evaluated the effect of BA on patients up to 12 months after COVID-19, characterized by reduced pulmonary function, dyspnea, and decreased oxygen saturation. MethodsPatients (n=392) were randomized 1:1 to receive BA (3000U) or placebo every 5 days for 71 days. Percent of predicted forced vital capacity (ppFVC), respiratory symptoms, and exercise tolerance indicators were assessed at baseline and on days 71 and 180. The primary endpoint was a change from baseline in ppFVC by Day 71. ResultsOn Day 71, BA was associated with a significant reduction in the proportion of patients with exertional desaturation (OR=0.35, p=0.0051) and dyspnea (OR=0.62, p=0.043). There were no significant intergroup differences in the ppFVC growth rate. Analysis of sub-populations revealed that by Day 180, BA was associated with increased ppFVC in patients with cardiovascular comorbidities (diff=3.31%, p=0.042) and those with earlier SARS-CoV-2 infection (diff=4.17%, p=0.021). BA was generally safe and well-tolerated. ConclusionIn patients with long-term pulmonary sequelae of COVID-19, BA was associated with increased exercise tolerance. There was evidence of shorter pulmonary function recovery time following BA in patients with cardiovascular comorbidities and those with earlier COVID-19 disease.