Efficacy of Fenofibrate for COVID-19: A phase II randomized controlled trial

PROJECT SUMMARYAging, obesity, diabetes, hypertension and other risk factors associated with abnormal lipid and carbohydratemetabolism are risk factors for death in Coronavirus disease 2019 (COVID-19).

Recent studies suggest thatCOVID-19 infection of human lung primary bronchial epithelial cells is dependent on metabolic mechanismsincluding a marked shift in cellular metabolism that leads to excessive intracellular lipid generation.

In this cellculture system, fenofibrate (a widely available low-cost generic drug approved by the FDA and multiple otherregulatory agencies around the world to treat dyslipidemias) at concentrations that can be achieved clinically,markedly inhibited SARS-CoV-2 viral replication. Fenofibrate also has immunomodulatory effects that may bebeneficial in the setting of COVID-19.

We propose an international multicenter randomized placebo-controlled trial to assess the impact offenofibrate on outcomes in patients with COVID-19.

We will administer fenofibrate (145 mg/d of Tricor or dose-equivalent preparations for 10 days, with dose adjustment in chronic kidney disease [CKD]) will be tested.

Ourprimary endpoint will be a global score that ranks patient outcomes according to 5 clinically important patient-centric outcomes.

Out hierarchical endpoint achieves high statistical power and thus maximized the likelihoodof productive phase II trials that can readily identify potential therapies for advance into phase III trials. We willassess various secondary and exploratory endpoints.

Finally, we aim to consolidate an international networkthat can rapidly execute phase II trials in COVID-19, leveraging established collaborations with COVID-19clinical researchers in Latin America. This network can readily execute this trial and support other NIH-fundedtrials.

Our proposal has the potential to advance a novel therapy (fenofibrate), a widely available, generic andinexpensive drug with a proven track record of safety. If fenofibrate is effective for COVID-19, our trial couldhave a major public health impact on the COVID-19 pandemic.