EPOXI: European randomised clinical trial in mPOX Infection

In 2022, a global outbreak of mpox occurred. It was spread by human-to-human transmission and particularly affected communities of men who have sex with men (MSM). Previously, the disease had been largely confined to Africa, where it primarily caused disease in rural communities and children, following contact with infected animals. Despite the significant decline of the epidemic outside of Africa, cases continue to be reported worldwide, including in Europe.

The mpox outbreak in Europe in 2022 emphasised the urgent need for effective treatments to reduce the impact on individuals and population health, as there is currently a lack of high-level evidence for antiviral treatment of mpox.

What is mpox?

Mpox is an acute febrile rash illness caused by the monkeypox virus, which has a fatality ratio reported between 3 and 6%. Human-to-human transmission can occur through various means, including close contact with infected individuals (such as sexual contact, exposure to respiratory secretions, and contact with skin lesions, etc) or recently contaminated objects.

To date, no data from randomised clinical trials are yet available for antiviral treatment of mpox.

EPOXI trial

The European randomised clinical trial in mPOX Infection (EPOXI) is an EU-funded clinical trial to determine the efficacy of tecovirimat, an antiviral drug, for the treatment of mpox. It is a Phase IV randomised placebo controlled double-blind interventional trial. The trial will take place in Belgium, France, Germany, Italy, the Netherlands, Norway, Portugal and Spain.

Patients who test positive for mpox infection will be randomly assigned in a 2:1 ratio to receive either a 14-day treatment of tecovirimat or a placebo, alongside standard care practices.

Eligibility and dosage

Adults 18 years or older with laboratory confirmed mpox. They may be (temporarily) hospitalised or treated as outpatients.
Adults with body weight ≥40kg will receive three capsules twice a day for 14 days (total daily tecovirimat dose: 1200 mg)
Pregnant or lactating women will be excluded.

Enrolment process

1. After the patient has been tested positive for mpox, the healthcare professional will inform the patient about their diagnosis and self-isolation requirements.

2. The healthcare professional will then provide information about the trial, with details on the participating centres and clinics. [option to hyperlink to the table below]

3. Following the patient’s verbal consent, the healthcare professional will share the patient’s contact details with the local study team.

4. The local EPOXI study team will contact the patient to discuss participation and answer questions about the trial.

5. If the patient wishes to join the trial, the study team will plan an in-person eligibility screening meeting to explain the study procedures.

6. If the patient is eligible and wishes to participate in the trial, they will be asked to sign an informed consent form.

“The recent mpox outbreak has underscored the potential global threat posed by this and the urgent need for randomised clinical trials to establish effective treatments. The data we gather from the EPOXI trial will be combined with data from other global mpox trials to achieve the required statistical power within a shorter timeframe.”
Principal Investigator Miquel Ekkelenkamp, UMC Utrecht, the Netherlands

Participating centres

Below you can find a list of the research centres and clinics participating in the EPOXI trial. The list will be expanded as additional sites join the trial.

Country	Hospital	Contact information
Belgium	Cliniques Universitaires Saint-Luc Brussels
Belgium	Institute of Tropical Medicine
France	APHP St Louis
Germany	Universitatsklinikum Bonn
Italy	Azienda Ospedaliera Universitaria Integrata Verona
Italy	Hospital Luigi Sacco
Netherlands	Amsterdam UMC - AMC
Norway	Oslo University Hospital
Portugal	Centro Hospitalar de Lisboa Central
Spain	Hospital Universitario Virgen Macarena
Spain	Hospital Clinico San Carlos
Spain	Hospital Universitario La Paz

About tecovirimat

Tecovirimat is an antiviral drug, with demonstrated activity in vitro and in animal models against several orthopox viruses, including smallpox, vaccinia, mpox and cowpox. Both the European Medicines Agency (EMA) and the Medicines and Healthcare products Regulatory Agency (MHRA) have granted tecovirimat marketing authorisation for the treatment of smallpox, cowpox and mpox, under an exceptional circumstances rule.

Based on preclinical data, tecovirimat may be effective in the treatment of mpox infection in humans. It works by inhibiting the cytopathic effect of monkeypox virus on cell cultures and has been found to protect non-human primates against lethal doses of monkeypox virus. (Siegrist 2022, Smith 2009, Jordan 2009). Safety studies with tecovirimat have been performed in healthy volunteers, and observational data on its use in mpox patients are available. However, data from randomised trials are still lacking.

MPX-RESPONSE

The EPOXI trial is part of the MPX-RESPONSE project which has received funding from the European Union’s Horizon Europe Research and Innovation programme under grant agreement No. 101115188.

Project duration: 5 August 2022 to 4 August 2026 (48 months)

Main trial endpoints: The primary clinical efficacy endpoint is the time to complete resolution of lesions, assessed until Day 28 (both cutaneous and mucosal lesions).

Project sponsor: University Medical Center Utrecht, the Netherlands

Collaborators: Ecraid, Erasmus University (the Netherlands), University of Antwerp (Belgium), Servicio Madrileño de Salud (Spain)

EUCT no. 2022-501979-10-00
Clinicaltrials.gov ID: NCT06156566

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