NCT05534165.

Study name	PLATINUM‐CAN
Methods	Study setting: community ‐ non‐hospitalized patients (including hospital emergency rooms, outpatient HIV and infectious diseases clinics, community sexual health clinics, primary care, or through public health services) Study design: multicentre, randomized (1:1), placebo‐controlled trial. Quadruple masking: participant, care provider, investigator, outcomes assessor Dates of recruitment: not yet recruiting (as of 29 September 2022) Eligibility criteria Inclusion criteria Any sex ≥ 18 years of age inclusive at the time of signing informed consent. Weight ≥ 40 kg Laboratory‐confirmed or presumptive mpox infection Laboratory‐confirmed mpox infection is defined as determined by PCR, culture, or antigen test obtained from a sample collected from blood, oropharynx, anal or skin lesion within 4 days of randomization OR Presumptive diagnosis: skin lesion(s), mucosal lesion(s) or proctitis consistent with a high probability of mpox infection in the opinion of the site investigator AND sexual contact with 1 or more persons in the 21 days prior to symptom onset or any person with known close exposure to another person known to be infected with mpox infection. Presence of active skin or mucosal lesion(s). Appropriate to be managed without hospitalization. The participant (or legally acceptable representative) has provided documented informed consent and comply to the required procedures for the study. Exclusion criteria Weight < 40 kg Current or past use of tecovirimat Inability to provide informed consent The patient's own doctor considers there to be either a definite indication or a definite contraindication to the patient receiving tecovirimat Participated in an interventional clinical study < 28 days prior to the day of first IP administration (Day 0) or plans to do so while enrolled in this study. Length of follow‐up: 28 days Loss to follow‐up: not applicable, ongoing Adherence to assigned treatment: not applicable, ongoing
Participants	Number of participants: 120 Source of participants: not stated Age: 18 years and older Sex: any Disease severity: not stated but non‐hospitalized patients so unlikely to be severe disease. Inclusion criteria state "able to be managed without hospitalisation". Vaccination status: not stated Concurrent treatments: not stated Pregnancy: not stated Comorbidities: not stated
Interventions	Intervention Therapeutic: tecovirimat Route of administration: oral capsule Dosage: 600 mg (administered as three 200 mg capsules) Timing: every 12 hours, 30 min after a meal Frequency: twice daily Duration of treatment: 14 days Duration of follow‐up: 28 days Control Type: identical placebo Route of administration: oral capsule Dosage: 600 mg (administered as three 200 mg capsules) Timing: every 12 hours, 30 min after a meal Frequency: twice daily Duration of treatment: 14 days Duration of follow‐up: 28 days
Outcomes	Primary Time (days) to active lesion resolution, defined as the first day on which all skin lesions are scabbed or desquamated (and mucosal lesions healed) up to 28 days after randomization. Feasibility and acceptability of conducting a pragmatic phase 3 interventional trial for outpatients with mpox in Canada, measured as the number of eligible patients per month and proportion randomized (up to 4 months). Secondary 1Time to complete lesion resolution (up to 28 days after randomization), defined as the time (days) to complete lesion resolution, defined as the first day on which all lesions are completely resolved (all scabs dropped off, and intact skin remains underneath, mucosal lesions healed). Time to negative throat swab viral culture (days 7, 14, 21, and 28), defined as time to consistently negative culture for mpox virus on throat swab Time to negative skin or mucosa swab viral culture (days 7, 14, 21, and 28), defined as time to consistently negative culture for mpox virus on swab of most recent active skin or mucosa. Secondary feasibility outcomes (4 months), defined as the proportion who adhere to at least 85% of daily questionnaires and self‐sampling, and the proportion of participants who are able to complete all protocol procedures. Other outcomes Clinical status (days 7, 14, 21 and 28). The ordinal scale is a) all lesions completely resolved (all scabs dropped off, and intact skin remains underneath, mucosal lesions healed), b) all active lesions resolved (all lesions scabbed, or desquamated, mucosal lesions healed), c) active lesions persist but no new lesions, d) new active lesions. Throat swab mpox DNA levels (days 7, 14, 21 and 28). Change from baseline in mpox virus DNA concentration in throat swabs Hospitalization rates (study duration). Number (%) of participants admitted to hospital for a complication of mpox, overall and by type Time to sustained absence of use of analgesia (up to 28 days postrandomization), defined as time to consistently reporting no use of analgesia. Assessment of safety (duration of study). Number (%) of participants suffering serious adverse events (overall and by type) up to 28 days of randomization. Number (%) of participants suffering adverse events of special interest (overall and by type) up to 28 days of randomization. Number (%) of participants suffering death, overall and by cause. Time to resolution of pain (28 days). Time to resolution of pain using an assessment for proctitis (rectal) and/or lesional pain comparing tecovirimat relative to placebo. Rate of improvement in overall quality of well‐being (28 days). Change in EuroQol‐ 5 Dimension (EQ‐5D) Quality Of Life scale. Validation of self‐reported time to active lesion resolution (28 days). Correlation between the time to active and complete resolution of lesions, in consenting participants, between self‐report and blinded photographic validation from an adjudication committee.
Starting date	Registered 9 September 2022
Contact information
Notes	Authors: Marina Klein, McGill University Title: Tecovirimat in Non‐hospitalized Patients with Monkeypox (PLATINUM‐CAN). Official titile: Placebo‐controlled Randomized Trial of Tecovirimat in Non‐hospitalized Patients with Monkeypox: Canadian Feasibility Study (PLATINUM‐CAN) Publication date: Ongoing, estimated completion date January 2023 Country: Canada Funding details: sponsors and collaborators: McGill University Health Centre/Research Institute of the McGill University Health Centre, University Health Network Toronto, Unity Health Toronto, University of British Columbia, CIHR Canadian HIV Trials Network CoI statement: not stated