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Camostat Does Not Relieve COVID
Symptoms or Clear Virus in Placebo Trial
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2022 CROI, February 12-16 and 22-24, 2022
Mark Mascolini
Despite strong lab data indicating that camostat can prevent SARS-CoV-2 infection of calls, this coronavirus protease inhibitor failed to lower viral load or improve COVID symptoms in a study of 215 outpatients with mild to moderate COVID [1].
Transmembrane protease serine 2 (TMPRSS2) is an enzyme essential to SARS-CoV-2 entry into target cells [2]. Camostat, a serine protease inhibitor, blocks the action of TMPRSS2 in cell studies and thus became a prime candidate for treating SARS-CoV-2 infection in humans [2]. In Japan and Korea, camostat has a good safety record when used in humans to treat postoperative reflux esophagitis and flares of chronic pancreatitis.
Researchers tested camostat in the ACTIV-2/A5401 platform trial, which can pit multiple agents against SARS-CoV-2 and compare them to a pooled placebo group. The phase 2 study enrolled adult outpatients with COVID-19 symptoms within the past 10 days. Participants took camostat at an oral dose of 200 mg every 6 hours for 7 days. Primary outcomes were nasal swab-collected virus below the lower limit detection on days 3, 7, and 14 and time to symptom resolution.
Of 224 people enrolled from February through April 2021, 215 received treatment and made up the modified intention-to-treat population. The 108 people randomized to camostat and the 107 randomized to placebo had median ages of 37 and 39, 57% and 51% were female at birth, 4% and 14% were black, and 56% and 46% were Hispanic. Almost half in each group, 47% and 46%, had symptoms that began within the past 5 days. About one quarter of each group, 27% and 24%, were judged at high risk for COVID progression.
Rates of grade 3 or worse adverse events did not differ substantially between the camostat group and the placebo group (7.4% and 6.5%); serious adverse event rates were also similar (5.6% and 4.7%).
On days 3, 7, 14, and 28, the camostat group and the placebo group did not differ in nasopharyngeal viral clearance (a primary endpoint) or viral decay. Nor did camostat takers differ from placebo takers in the other primary endpoint, time to "all targeted symptoms improved." The curves and box plots for these outcomes virtually overlapped for camostat and placebo.
Cumulative hospital admission numbers were nearly identical for camostat and placebo (108 and 107), as were deaths (6, 5.6% with camostat versus 5, 4.7% with placebo).
Camostat did not meet virologic or clinical criteria to enter phase 3 trials. This protease inhibitor "is safe but did not show clinical or virologic efficacy in outpatients with COVID-19 highlighting the critical importance of randomized controlled trials," the researchers concluded.
References
1. Jilg N, Chew KW, Giganti M, et al. Camostat is not effective for mild-moderate COVID-19 in a phase II trial of ACTIV-2. 2022 CROI, February 12-16 and 22-24, 2022. Abstract 105.
2. Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 202;181:271-280.e8.doi: 10.1016/j.cell.2020.02.052. https://www.cell.com/cell/fulltext/S0092-8674(20)30229-4
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