Protocol of Tecopox study: a multicentre, open-label, double-arm trial to evaluate the efficacy and safety of oral tecovirimat therapy for patients with smallpox or monkeypox

INTRODUCTION: Monkeypox was originally endemic locally in West Africa; however, outbreaks in non-endemic countries have been recognised since May 2022. The effectiveness of tecovirimat has been estimated against smallpox, which belongs to the same Orthopoxvirus genus as monkeypox. Thus, tecovirimat is expected to be effective against monkeypox. This study aims to evaluate the efficacy and safety of oral tecovirimat therapy for patients with smallpox and monkeypox and to prepare a scheme for oral tecovirimat use in Japan. METHODS AND ANALYSIS: This nationwide, multicentre, non-randomised, open-label, double-arm study will involve viral examination of the blood, throat swabs, urine and skin lesions, performed periodically. Participants will freely decide whether to participate in an administered group (supportive treatment plus oral tecovirimat) or a non-administered group (only supportive treatment). Tecovirimat will be administered for 14 days. To ensure that financial problems do not preclude participation in the study, the research fund will cover the cost of tecovirimat and basic hospitalisation fees. The primary endpoint is the percentage of patients with negative PCR results (cycle threshold value ≥40) for skin lesion specimens at 14 days after inclusion in the study. Secondary endpoints include mortality at 14 and 30 days, viral load in each sample, duration of fever and adverse events. The sample size is estimated to be 50 patients with monkeypox or smallpox. ETHICS AND DISSEMINATION: Written informed consent will be obtained from all participants. This study was approved by the Certified Review Board of National Center for Global Health and Medicine and published in the Japan Registry of Clinical Trials. The results of this study will be published in peer-reviewed journals and/or in presentations at academic conferences. TRIAL REGISTRATION NUMBER: jRCTs031220169.