Research question
Does Tecoviramat reduce the duration of infectiousness in patients with confirmed monkeypox infection when compared to usual care?
- Patient group: Patients diagnosed with confirmed monkeypox, not being managed in hospital.
- Intervention: Usual care plus Tecoviramat, dose and regimen to be defined in conjunction with UKHSA colleagues.
- Comparator: Usual care, applicants to define and justify.
- Primary outcome: Duration of infectiousness. Applicants should define and justify the robust method by which this will be measured
- Other important outcomes: Duration of symptoms; adverse events.
- Setting: Outpatient settings managing patients with monkeypox. Current likely settings include sexual health clinics, but applicants must demonstrate that they can alter their recruitment strategy should the epidemiology of the disease change.
- Study design: open label 2-Arm parallel group individually randomised controlled trial, with the potential to pause should patient numbers drop.
- Minimum duration of follow-up: Minimum 28 days.
Rationale
Historically, monkeypox has been rare outside west and central Africa, An outbreak has started in early May 2022, initially in the UK, but now with cases appearing in other atypical countries. In the UK, community transmission has been noted in London, particularly in men who have sex with men. The variety currently circulating in the UK is the West African clade, which is expected to have a case fatality rate of less than 3%.
There are two drugs which may be considered for treatment of monkeypox, brincidofovir and tecoviramat. Tecoviramat (a.k.a. ST-246) is a novel antiviral which inhibits the function of VP37 envelope protein of orthopoxviruses and thereby prevents the virus from leaving the infected cell. As tecoviramat is licensed in the EU and USA, with good orally bioavailablity, it is a suitable candidate treatment for outpatients. Brincidofovir has weaker efficacy data derived from primate models, and so is not being considered as a treatment agent in the UK at this time.
NIHR therefore wishes to commission a phase 2 study to investigate the efficacy of tecoviramat for the management of monkeypox in a non-hospitalised population. The study would need to be efficient, with the study sample size compatible with likely available patient numbers.
Call specific notes
The proposed study is expected to be able to be responsive to changes in the epidemiology of the disease. This might involve the affected populations becoming larger, or alternatively the number of cases might diminish, possibly to the point where the study might need to be hibernated to be reactivated should disease incidence increase. Applicants should demonstrate that their proposed team has both managerial and clinical expertise to deal with these possibilities.
Randomisation processes should take into account patient vaccine status, particularly whether they have received Imvanex (or other licensed orthopoxvirus vaccine)
Due to the need to inform service commissioners, NIHR expects the successful team to be able to randomise patients within 14 days of a funding decision, subject to rapid approvals processes with HRA and MHRA, and procurement.
DHSC is arranging for supply of tecovirimat for both treatment and research purposes. The study team will have access to this supply to provide study drug and will need to arrange for drug distribution to participants.
NIHR expects to see appropriate attention given to PPIE, and a clear strategy to engage the affected populations, and this will be assessed by the funding committee.
Applicants are requested not to include UKHSA co-applicants. The UKHSA will work with the successful applicants to deliver the study, and UKHSA investigator and researcher involvement should be costed appropriately. Proposals can be discussed with Meera Chand (cei@phe.gov.uk) at the UKHSA before submission.
Due to the rapid development of this call in a rapidly evolving area, if further relevant information becomes available from stakeholders the brief may be updated in the next 24 hours. If you are considering applying please start an application on the Management Information System or email eme@nihr.ac.uk and we will provide you with details of any updates.