Research project The rapid spread and severity of Covid-19, and lack of effective drugs is a global medical emergency. Can a drug commonly used to treat prostate cancer be used to reduce the severity of Covid-19?
COVIDENZA is a multi-centre randomized clinical trial investigating if enzalutamide may be beneficial in COVID-19. Men have higher risk of severe symptoms of COVID-19, the reason is unknown, but may be due to the androgens, male sex steroids. Studies, both epidemiological and experimental, support our hypothesis that the antiandrogen drug Enzalutamide may limit the severity of Covid-19 symptoms.
There are millions of cases of the new corona virus disease COVID-19 in the world, resulting in hundreds of thousands of deaths and a huge strain on global health services. Despite a similar apparent infection rate, men account for the majority of serious cases and deaths (74% of ICU cases in Sweden, 1373 of 1853, Folkhälsomyndigheten, 18/5/2020). This trend is seen globally which suggests factors other than cultural or behavioural in action.
The more severe disease pattern among men may be related to testosterone and androgen receptor signalling. An enzyme called transmembrane protease, serine 2 (TMPRSS2) is regulated by the androgen receptor and is upregulated in prostate cancer. As TMPRSS2 was recently demonstrated to be involved in the mechanism by which Sars-CoV-2 virus enters cells, this could be affected by the androgen receptor. It is also known that androgens affect the immune system, which may impact COVID-19 morbidity.
The basis for this study is the hypothesis that the widely used anti-androgen drug Enzalutamide may reduce androgen driven morbidity in COVID-19, e.g. by reduction of Sars-CoV-2 entry into cells. Androgen signaling is also present in females and a therapeutic effect by androgen inhibition may therefore also be beneficial in women.
Hospitalized COVID-19 patients (over 50 yrs of age) will be randomized 2:1 between 5 days enzalutamide + standard of care (experimental arm) or standard of care (control arm). Disease severity (7-point ordinal scale, length of hospital stay, requirement for oxygen, adverse events, and laboratory parameters) will be monitored. The trial will have two interim analyses, at 45 and 100 included patients for safety and power calculations, respectively. The trial is designed to be able to include up to 600 patients.
Trial start is planned for the 8th of June.
Karin Welén, Gothenburg
Magnus Gisslen, Gothenburg
Johan Stranne, Gothenburg
Karlis Pauksens, Uppsala
Anna Bill Axelsson, Uppsala
Olof Akre, Stockholm
Tobias Nordstrom, Stockholm
David Robinsson, Jönköping
Anna Jonsson Henningsson, Jönköping
Anders Bjartell, Malmö
Anna Nilsson, Malmö
Eva Freyhult, Uppsala/Umeå
Johan Styrke, Sundsvall
Johanna Repo, Sundsvall
Cecilia Ryden, Helsingborg
Magnus Wagenius, Helsingborg
Camilla Thellenberg, Umeå
Astellas Pharma Europe ltd. support the trial with unconditional grants, and have no influcene on the protocol, managment of the trial, or future analysis. Wallenberg Center for Molecular Medicine support the trial.