Clinical trial NCT05534165: Tecovirimat in Non-hospitalized Patients With Monkeypox
Official title: Placebo-controlled Randomized Trial of Tecovirimat in Non-hospitalized Patients With Monkeypox: Canadian Feasibility Study (PLATINUM-CAN)
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE3
Conditions: Monkeypox
Keywords: Tecovirimat
Randomized
Placebo-Controlled
Outpatients
Non-hospitalized
Feasibility
Lead sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre
Sponsor class: OTHER
Collaborators: name: McGill University Health Centre/Research Institute of the McGill University Health Centre
name: University Health Network, Toronto
name: Unity Health Toronto
name: University of British Columbia
name: CIHR Canadian HIV Trials Network
First posted: 2022-09-09
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized 1:1
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Time to active lesion resolution
timeFrame: Up to 28 days after randomization
measure: Feasibility and acceptability of conducting a pragmatic phase 3 interventional trial for outpatients with Monkeypox in Canada
timeFrame: 4 months
Secondary outcomes:
measure: Time to complete lesion resolution
timeFrame: Up to 28 days after randomization
measure: Time to negative throat swab viral culture
timeFrame: Days 7, 14, 21, and 28
measure: Time to negative skin or mucosa swab viral culture
timeFrame: Days 7, 14, 21, and 28
measure: Secondary feasibility outcomes
timeFrame: 4 months
Other outcomes:
measure: Clinical status
timeFrame: day 7, 14, 21 and 28
measure: Throat swab monkeypox DNA levels
timeFrame: day 7, 14, 21 and 28
measure: Hospitalization rates
timeFrame: study duration
measure: Time to sustained absence of use of analgesia
timeFrame: Up to 28 days post randomization
measure: Assessment of safety
timeFrame: Duration of study
measure: Time to resolution of pain
timeFrame: 28 days
measure: Rate of improvement in overall quality of well-being
timeFrame: 28 days
measure: Validation of self reported time to active lesion resolution
timeFrame: 28 days
Locations:
city: Vancouver
country: Canada
facility: St. Paul's Hospital, BC Centre for Excellence in HIV/AIDS
state: British Columbia
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
Study officials:
References: