Tecovirimat in Non-hospitalized Patients With Monkeypox (PLATINUM-CAN)

Placebo-controlled Randomized Trial of Tecovirimat in Non-hospitalized Patients With Monkeypox: Canadian Feasibility Study (PLATINUM-CAN)

PLATINUM-CAN is a parallel collaborative trial linked with the sister trial PLATINUM led by Oxford University. PLATINUM-CAN is a multi-centre, randomized, placebo-controlled trial of Tecovirimat in non-hospitalized patients with presumptive or PCR confirmed monkeypox infection. The study will provide evidence on the efficacy and safety of Tecovirimat for laboratory-confirmed monkeypox in outpatients with monkeypox infection and determine the feasibility of conducting interventional monkeypox trials in Canada.

Study Overview

• Status: Suspended
• Conditions: Monkeypox
• Intervention / Treatment: Drug: Tecovirimat; Drug: Placebo

Detailed Description

In order to generate needed therapeutic efficacy evidence rapidly, international collaboration is essential. PLATINUM-CAN is a parallel collaborative trial linked with the sister trial PLATINUM led by Oxford University. Given the rapidly evolving epidemic and important differences in healthcare contexts and public health systems between countries that could impact the number of cases and access to diagnosis and treatment, a Canadian study is warranted to assess the feasibility and acceptability of conducting large scale interventional monkeypox trials in Canada. Such a focused trial also allows for the opportunity to explore a number of secondary objectives that can address concerns raised during consultation with Canadian community members (e.g., resolution of pain, quality of life) and validate use of self-assessed primary outcomes using blinded photography assessment.

The trial is pragmatic and minimizes number of visits, tests performed and contacts with the healthcare system through use of self-assessment diaries and self-testing. Lesion and/or throat swabs taken as part of standard care will be sent for detection of monkeypox virus DNA by PCR to local public health/provincial laboratories for initial screening (using panorthopox DNA testing) and confirmation with monkeypox specific PCR either locally or by National Microbiology Laboratory. The protocol allows for a broad range of patients to be enrolled. The trial has been designed so that it can accommodate patients who may be assessed in a variety of medical settings (e.g., hospital emergency rooms, outpatient HIV and infectious diseases clinics, community sexual health clinics, primary care, or through public health services). Similarly, we will ensure our trial design is able to contribute to global efforts such as the core protocol for the evaluation of treatments for human monkeypox (led by the Institut National de Recherche Biomédicale (INRB)/ANRS/NIAID in collaboration with WHO) and the AIDS Clinical Trials Group (ACTG) STOMP protocol.

As a feasibility study, PLATINUM CAN is underpowered for evaluating a primary endpoint of time to active lesion resolution. To achieve full study power, results will be combined with the sister study, PLATINUM-UK (n=500), being conducted at Oxford University, UK of similar design using a pre-planned individual patient meta-analysis. In addition to feasibility outcomes, the trial will evaluate the correlation between the time to active and complete resolution of lesions between self-report and blinded photographic validation from an adjudication committee, in consenting participants.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 1Y6
      • St. Paul's Hospital, BC Centre for Excellence in HIV/AIDS
  • Ontario
    • Toronto, Ontario, Canada, M5B 1W8
      • St. Michael's Hospital
    • Toronto, Ontario, Canada, M5G 2N2
      • Toronto General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Any sex, ≥ 18 years of age inclusive at the time of signing informed consent.
2. Weight ≥ 40 kg

3. Laboratory-confirmed or presumptive monkeypox infection:

   Laboratory-confirmed monkeypox 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 monkeypox 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 monkeypox infection. Presence of active skin or mucosal lesion(s).
4. Appropriate to be managed without hospitalization.
5. The participant (or legally acceptable representative) has provided documented informed consent and comply to the require procedures for the study.

Exclusion Criteria:

1. Weight < 40 kg
2. Current or past use of tecovirimat
3. Inability to provide informed consent
4. The patient's own doctor considers there to be either a definite indication or a definite contraindication to the patient receiving tecovirimat
5. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tecovirimat; Tecovirimat (TPOXX®) Capsules, 200 mg (as tecovirimat monohydrate) administered as 600 mg (three 200 mg capsules) taken twice daily orally, every 12 hours, within 30 minutes after a full meal of moderate or high fat (approximately 25 g of fat) for 14 days	Drug: Tecovirimat; 600 mg po BID; Other Names: TPOXX
Placebo Comparator: Placebo; Identical placebo supplied by SIGA Technologies Inc.	Drug: Placebo; identical placebo 600 mg po BID

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to active lesion resolution	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 Monkeypox in Canada	Number of eligible patients per month and proportion randomized	4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to complete lesion resolution	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)	Up to 28 days after randomization
Time to negative throat swab viral culture	Defined as time to consistently negative culture for monkeypox virus on throat swab	Days 7, 14, 21, and 28
Time to negative skin or mucosa swab viral culture	Defined as time to consistently negative culture for monkeypox virus on swab of most recent active skin or mucosa	Days 7, 14, 21, and 28
Secondary feasibility outcomes	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	4 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical status	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.	day 7, 14, 21 and 28
Throat swab monkeypox DNA levels	Change from baseline in monkeypox virus DNA concentration in throat swabs	day 7, 14, 21 and 28
Hospitalization rates	Number (%) of patients admitted to hospital for a complication of monkeypox, overall and by type	study duration
Time to sustained absence of use of analgesia	defined as time to consistently reporting no use of analgesia	Up to 28 days post randomization
Assessment of safety	Number (%) of patients suffering serious adverse events (overall and by type) up to 28 days of randomization; Number (%) of patients suffering adverse events of special interest (overall and by type) up to 28 days of randomization; Number (%) of patients suffering death, overall and by cause	Duration of study
Time to resolution of pain	Time to resolution of pain using an assessment for proctitis (rectal) and/or lesional pain comparing tecovirimat relative to placebo	28 days
Rate of improvement in overall quality of well-being	Change in EuroQol- 5 Dimension (EQ-5D) Quality Of Life scale	28 days
Validation of self reported time to active lesion resolution	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	28 days

Collaborators and Investigators

• Sponsor: Marina Klein
• Collaborators: University Health Network, Toronto; University of British Columbia; McGill University Health Centre/Research Institute of the McGill University Health Centre; Unity Health Toronto; CIHR Canadian HIV Trials Network

Study record dates

Study Major Dates

• Study Start (Actual): August 14, 2023
• Primary Completion (Actual): March 13, 2025
• Study Completion (Estimated): March 31, 2026

Study Registration Dates

• First Submitted: September 2, 2022
• First Submitted That Met QC Criteria: September 7, 2022
• First Posted (Actual): September 9, 2022

Study Record Updates

• Last Update Posted (Actual): March 4, 2026
• Last Update Submitted That Met QC Criteria: March 3, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Feasibility; Randomized; Outpatients; Placebo-Controlled; Non-hospitalized; Tecovirimat
• Additional Relevant MeSH Terms: Infections; Virus Diseases; Poxviridae Infections; DNA Virus Infections; Animal Diseases; Primate Diseases; Rodent Diseases; Mpox, Monkeypox; Anti-Infective Agents; Antiviral Agents; tecovirimat
• Other Study ID Numbers: CTN 338

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No