Cohort study of human mpox virus disease

The primary objective of this cohort study is to describe the **clinical outcomes** in patients with **monkeypox virus disease** who are treated and not treated with **tecovirimat** or other antiviral drugs. This objective is clinically relevant as it aims to evaluate the effectiveness of antiviral treatments in managing the disease, which can inform treatment protocols and improve patient care.

Secondary objectives include:

• Describing other clinical outcomes in patients with monkeypox virus disease treated and not treated with tecovirimat or other antiviral drugs.
• Describing virological outcomes in patients with monkeypox virus disease treated or not treated with tecovirimat or other antiviral drugs.
• Describing safety outcomes in patients with monkeypox virus disease treated with tecovirimat or other antiviral drugs.

The clinical trial involves a total of **600 participants** diagnosed with **Monkeypox virus disease**. The study population includes both male and female subjects, encompassing a diverse age range. Participants were selected based on either laboratory-confirmed diagnosis or pending laboratory confirmation while being managed as presumptive cases. Informed consent was a prerequisite for inclusion in the study. The trial population includes individuals from vulnerable groups, ensuring a comprehensive understanding of the disease's impact across different demographics. Lifestyle factors such as diet, physical activity, and habits were not specified by the sponsor. The study aims to evaluate clinical outcomes in patients treated and not treated with **tecovirimat** or other antiviral drugs.

The clinical trial is designed to evaluate the **clinical outcomes** in patients with **monkeypox virus disease**, both treated and untreated with **tecovirimat** or other antiviral drugs. This is a Phase IV, low-intervention cohort study, with an estimated recruitment start date of June 27, 2022, and an anticipated end date of January 31, 2024. The trial employs a randomized, double-blind, controlled design to ensure the reliability and validity of the results. Participants will be involved in the study for a maximum treatment period of 14 days, with the possibility of early termination if serious adverse events occur or if the participant withdraws consent.

The sequence of study visits begins with an inclusion (screening) visit, where eligibility is confirmed based on criteria such as laboratory-confirmed monkeypox virus disease or pending confirmation with presumptive management. Informed consent is required for participation. Follow-up visits are scheduled on days 4, 8, 14, and 28 to assess clinical and virological status, including changes in **monkeypox virus DNA** levels in throat, blood, and lesion swabs. The primary endpoint is the time to lesion resolution, defined as the first day all lesions are resorbed, scabbed, or desquamated, and mucosal ulcers healed, without serious complications, within 14 days of inclusion or treatment commencement.

Secondary endpoints include clinical status on days 14 and 28, evidence of recrudescence or relapse at days 60 and 180, and the number and type of serious adverse events within 28 days of enrollment. The end-of-study visit will evaluate the overall clinical status and virological outcomes, ensuring comprehensive data collection for analysis. Participants may be withdrawn from the study if they experience serious complications or if the study is terminated early for any reason. The trial aims to provide valuable insights into the management of monkeypox virus disease and the efficacy of **tecovirimat** as a treatment option.

The clinical trial involves the administration of **Tecovirimat SIGA 200 mg hard capsules** as the experimental medication. Tecovirimat is a chemical substance, and the pharmaceutical form is a hard capsule. The medication is administered orally. The maximum daily dose is 1200 mg, and the total maximum dose over the treatment period is 16800 mg. The treatment period is limited to a maximum of 14 days. The medication is manufactured by SIGA TECHNOLOGIES NETHERLANDS B.V. and is not a pediatric formulation. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the prescribed regimen.

In addition to the experimental treatment, the study may include non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments, as applicable. These treatments will be administered according to the standard protocols and guidelines relevant to the management of mpox virus disease. The trial aims to evaluate the clinical outcomes in patients with mpox virus disease who are treated with tecovirimat compared to those who are not treated with antiviral drugs. The study will ensure that all participants receive appropriate care and monitoring throughout the trial duration.

Efficacy in the clinical trial for human **mpox virus** disease will be assessed using both primary and secondary endpoints. The primary endpoint is the time to lesion resolution, which is defined from the date a positive test is collected or treatment is initiated, up to 14 days since inclusion or treatment commencement. Lesion resolution is characterized by all lesions being resorbed, scabbed, or desquamated, mucosal ulcers healed, and the absence of any serious complications.

Secondary endpoints include clinical status and virological status. Clinical status will be evaluated on days 14 and 28 using an ordinal scale assessed by a physician or study nurse, with categories ranging from all lesions resolved with no serious complications to death. Evidence of recrudescence or relapse will be assessed at days 60 and 180. Virological status will be determined by changes from baseline in mpox virus DNA levels in throat swabs and blood on days 4, 8, 14, and 28, as well as the presence of virus DNA in lesion swabs on the same days.

In the cohort receiving tecovirimat or other antivirals, the number and type of Serious Adverse Events (SAEs), Suspected Adverse Reactions (SARS), and Suspected Unexpected Serious Adverse Reactions (SUSARs) will be recorded within 28 days of enrollment. Additionally, the outcome of pregnancy in women who are pregnant will be monitored. These assessments will provide comprehensive data on the efficacy of the treatment regimen in managing mpox virus disease.