A phase 2a double-blind, placebo-controlled randomized trial of the SARS-CoV-2-specific monoclonal antibody AER002 in people with Long COVID

Long COVID is a disabling chronic illness with no proven treatments. Persistence of SARS-CoV-2 has been proposed as a biological driver of the disease. We conducted a placebo-controlled, double-blind, 2:1 randomized mechanistic trial of the SARS-CoV-2-specific monoclonal antibody AER002 in 36 participants who met the World Health Organization case definition of Long COVID. After baseline characterization, participants received a single infusion and were followed for 360 days. The primary endpoint was the PROMIS-29 Physical Health Summary Score (PHSS) at 90 days; secondary and exploratory endpoints included patient-reported and objective measures of physical, cognitive, and neurologic function as well as blood-, imaging-, and tissue-based biomarkers. While AER002 was safe and well tolerated, no significant differences in physical health, quality of life, objective measures of physical function or cognition, or blood-based biomarkers were demonstrated between the treatment and control arms. In a post-hoc analysis, participants with a lower baseline SARS-CoV-2 antibody level and higher drug exposure were more likely to express a perceived treatment benefit based on the Patient Global Impression of Change scale (p<0.05 for anti-S, S1, and RBD). Although AER002 was not efficacious in this proof-of-concept study of people with broadly defined Long COVID, our findings could inform recruitment or dosing strategies employed in future trials using monoclonal antibodies to target viral persistence as a driver of Long COVID.