Prospective Study of Treatment with Ensitrelvir for COVID-19 in Patients Undergoing Hemodialysis (PROTECT-HD).

INTRODUCTION

Patients on hemodialysis (HD) are vulnerable to COVID-19 and often excluded from pivotal antiviral trials. Ensitrelvir, an oral SARS-CoV-2 3C-like protease inhibitor approved in Japan, remains unevaluated in patients undergoing HD. This study assesses the pharmacokinetics, antiviral activity, safety, and clinical effectiveness of ensitrelvir in participants with mild COVID-19 undergoing HD.

METHODS

In this prospective, single-arm, open-label study (December 2024-April 2025), participants with mild COVID-19 undergoing HD received ensitrelvir 375 mg on Day 1, followed by 125 mg once daily on Days 2-5. On Visit 2 (Day 3), plasma ensitrelvir concentrations were measured at three time points prior to ensitrelvir administration-before, during, and after dialysis. On Visit 3 (Day 5), blood samples were collected after dialysis and prior to ensitrelvir administration. Clinical outcomes, body temperature, SARS-CoV-2 viral load, and viral titers were monitored through Day 8. The primary endpoint was plasma concentration of ensitrelvir relative to dialysis; secondary endpoints included clinical outcomes, body temperature, and changes in viral load.

RESULTS

Eight participants were evaluated: mean age, 68.1 years; mean body weight, 58.0 kg; and mean body mass index, 24.1 kg/m2. Plasma ensitrelvir concentrations (geometric mean) remained stable, with similar levels before (18.0 µg/mL) and after dialysis (16.4 µg/mL). All participants were judged clinically effective by the investigator by Day 8. Body temperature normalized within 16.6-48.0 h in four participants, and in one participant after 59.2 h. SARS-CoV-2 viral load (mean ± standard deviation) declined by 2.85 ± 1.52 log10 copies/mL from baseline to Day 8. No treatment-emergent adverse events, hospitalizations, or severe COVID-19-related complications occurred.

CONCLUSION

No dose adjustment was required regardless of HD. In participants with mild COVID-19 undergoing HD, plasma ensitrelvir concentrations were similar to those previously reported in healthy individuals. Ensitrelvir showed favorable antiviral and clinical responses, supporting its safe use without dose adjustments.

TRIAL REGISTRATION: Japan Registry of Clinical Trials ID: jRCTs071240069.