NCT05597735.

Study name	UNITY
Methods	Study setting: mixed, most participants will be managed at home or in the community. Study design: randomized, placebo‐controlled trial Dates of recruitment: not yet recruiting Inclusion criteria Adults and adolescents (14 years old and older) with laboratory‐confirmed (PCR if available) or highly suspected mpox virus infection of any duration At least one visible active skin or mucosal lesion Reachable via smartphone (for video calls) for outpatient participants Signed informed consent Exclusion criteria Current or planned use of another investigational drug at any point during study participation. Ongoing treatment which cannot be interrupted and for which a major interaction has been described with tecovirimat People who, in the judgement of the investigator, will be at significantly increased risk as a result of participation in the study (for example: if the investigator judges that an antiviral treatment is indicated in the framework of compassionate therapeutic access in Switzerland). Hypersensitivity to tecovirimat Length of follow‐up: 60 days Loss to follow‐up: not stated, ongoing Adherence to assigned treatment: not stated, ongoing
Participants	Number of participants: 150 Sex: male and female Disease severity: any severity, must have at least one active lesion Vaccination status: not stated, ongoing Concurrent treatments: not stated, ongoing Pregnancy: not stated, ongoing Comorbidities: not stated, ongoing
Interventions	Intervention Therapeutic: tecovirimat Route of administration: immediate‐release oral capsules containing tecovirimat monohydrate Dosage, frequency and timing: 200 mg, dosed on weight: 25 kg to < 40 kg: 400 mg (two tecovirimat 200 mg capsules) every 12 hours for 14 consecutive days. 40 kg and above: 600 mg (three tecovirimat 200 mg capsules) every 12 hours for 14 consecutive days. 6 to < 13 kg: half the contents of a capsule twice daily (total daily tecovirimat dose: 200 mg) 3 to < 6 kg: one quarter of the contents of a capsule twice daily (total daily tecovirimat dose: 100 mg) Duration of treatment: 14 days Duration of follow‐up: 28 days follow‐up and long‐term assessment at 60 days Control Route of administration: oral capsule Dosage, frequency and timing: to match intervention group Duration of treatment: 14 days Duration of follow‐up: 28 days follow‐up and long‐term assessment at 60 days
Outcomes	Primary Time to all visible lesion resolution (up to day 28) defined as time for all visible lesions (skin, mucosal) to heal with a new fresh layer of skin re‐epithelialization (i.e. resurfacing of a wound with a new epithelium layer). For skin lesions, typically this means the lesion has scabbed, desquamated and new layer of skin has been formed. For mucosal lesions, the phase of scabbing and desquamation is absent, and healing with new layer of skin ensues. Secondary All‐cause mortality within the first 28 days (applies to all participants) (up to day 28) All‐cause unplanned admission to hospital within first 28 days (applies to outpatients) Occurrence of participants with a complication within first 28 days (applies to all participants who did not already have a complication at baseline) Time to resolution of symptoms and signs within first 28 days (applies to all participants) Viral clearance up to 28 days after randomization Frequency of adverse events and serious adverse events for specific therapeutics (applies to all participants) (up to day 60)
Starting date	Registered 1 November 2022
Contact information
Notes	Authors: Study director Yazdan Yazdapanah, Pr. ANRS, Emerging Infectious Diseases Alexandra Calmy alexandra.calmy@hcuge.ch Olivier Segeral olivier.segeral@hcuge.ch Title: Assessment of the Efficacy and Safety of Tecovirimat in Patients with Monkeypox Virus Disease (UNITY) Country: Brazil, Switzerland Date(s) of study: estimated primary completion January 2024 Estimated actual completion: January 2025 Funding details: Calmy Alexandra, Oswaldo Cruz Foundation, ANRS, Emerging Infectious Diseases CoI statement: not stated

CoI: conflict of interest; PCR: polymerase chain reaction