Tecovirimat in Non-hospitalized Patients With Monkeypox

Monkeypox Clinical Trial

— PLATINUM-CAN  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05534165
• Other study ID #: CTN 338
• Status: Recruiting
• Phase: Phase 3
• Start date: August 14, 2023
• Est. completion date: March 2025

Study information

• Verified date: February 2024
• Source: McGill University Health Centre/Research Institute of the McGill University Health Centre
• Contact: Hansi Peiris
• Phone: 514-934-1934
• Email: hansi.peiris[@]muhc.mcgill.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: March 2025
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Monkeypox

Intervention

Drug:
• Tecovirimat
600 mg po BID
• Placebo
identical placebo 600 mg po BID

Locations

Country	Name	City	State
Canada	St. Michael's Hospital	Toronto	Ontario
Canada	Toronto General Hospital	Toronto	Ontario
Canada	St. Paul's Hospital, BC Centre for Excellence in HIV/AIDS	Vancouver	British Columbia

Sponsors (6)

Lead Sponsor	Collaborator
Marina Klein	CIHR Canadian HIV Trials Network, McGill University Health Centre/Research Institute of the McGill University Health Centre, Unity Health Toronto, University Health Network, Toronto, University of British Columbia

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	Throat swab monkeypox DNA levels	Change from baseline in monkeypox virus DNA concentration in throat swabs	day 7, 14, 21 and 28
Other	Hospitalization rates	Number (%) of patients admitted to hospital for a complication of monkeypox, overall and by type	study duration
Other	Time to sustained absence of use of analgesia	defined as time to consistently reporting no use of analgesia	Up to 28 days post randomization
Other	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
Other	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
Other	Rate of improvement in overall quality of well-being	Change in EuroQol- 5 Dimension (EQ-5D) Quality Of Life scale	28 days
Other	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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	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