The University of Alabama at Birmingham (UAB) and Mereo BioPharma Group plc (NASDAQ: MREO), today announced top-line data from a Phase 1b/2 clinical trial evaluating alvelestat, a novel, orally active Neutrophil Elastase (NE) inhibitor in hospitalized COVID-19 Respiratory Disease patients.
The COSTA Phase 1b/2 trial (NCT04539795) is an investigator-led, single-centre study (Principal Investigator Dr. James M Wells, Associate Professor in Pulmonary, Allergy and Critical Care Medicine, UAB). The trial is a double-blind, randomized, placebo-controlled study in adult patients (>18 years) with COVID-19 Respiratory Disease, evaluating the safety and tolerability of alvelestat on top of Standard of Care in patients hospitalised with proven COVID-19 lung disease. Patients requiring mechanical ventilation were excluded. Enrolled subjects received alvelestat or matched placebo, twice daily, for 5 days, with optional extension to 10 days per investigator judgement. Initial subjects underwent dose escalation to evaluate safety and tolerability for the population. The Primary Endpoint was Safety and Tolerability to Day 60, with mortality assessment at Day 90. Secondary Endpoints were clinical outcomes to Day 60. Biomarkers of inflammation, coagulopathy, were measured; biomarkers of neutrophil extracellular traps (NETs) were explored and desmosine was measured to the end of study drug treatment. The study was signal seeking and not powered for the secondary measures.
Fifteen patients were randomized (10 male, 5 female), and all completed the Primary Endpoint Safety assessment to Day 60 and the Day 90 final study assessment. The original design involved a 2:1 active to placebo ratio, however patients were enrolled 1:1 resulting in 8 patients on alvelestat and 7 patients on placebo. The mean age was 47.8 years; the most common co-morbidities were hypertension, sleep apnea, hypercholesterolemia, and Type 2 diabetes. At entry to the study, all patients were requiring supplemental oxygen, all had initiated dexamethasone and 14 were on antiviral treatment with remdesivir at baseline or initiated after randomization (7/7 on placebo and 7/8 on alvelestat). The majority of patients were WHO COVID-19 Ordinal Severity Scale Score 4 (hospitalized mild disease requiring supplemental oxygen) or 5 (hospitalized severe disease, requiring non-invasive ventilation or high flow oxygen) at entry to the study.