Periodic Reporting for period 2 - MPX-RESPONSE (A clinical research network to improve the management of Monkeypox virus disease)
Reporting period: 2023-08-05 to 2024-08-04
Mpox is an acute febrile rash illness caused by the mpox virus, often accompanied by symptoms such as fever, headache, or muscle aches.
Before 2022, travel-related cases outside Africa were rare, and onward transmission was limited. However, in May 2022, an unprecedented global outbreak led the World Health Organization (WHO) to declare mpox a Public Health Emergency of International Concern (PHEIC). Although cases outside of Africa declined rapidly by the end of summer 2022, cases continue to be reported in previously unaffected regions (i.e. South America, Europe), signaling a potential shift from an epidemic outbreak to an endemic worldwide presence of the virus. In Africa, the Democratic Republic of Congo (DRC) and neighboring countries continue to face a concerning number of cases, along with the emergence of a new clade. This situation prompted the WHO to re-declare mpox a PHEIC in August 2024. Continuous surveillance remains crucial.
The MPX-RESPONSE project aims to deepen our understanding of mpox, including its transmission patterns, and the evolution of the disease (MOSAIC cohort; WP2). The project will also assess the efficacy and safety of antiviral treatments through randomized clinical trials in three different regions of the world (UNITY, EPOXI and MOSA). Therefore, another important project’s outcome will be the validation (or not) of existing antiviral treatments for the mpox indication (WP3; WP4).
Finally, the project will contribute to enhance Europe’s preparedness for future health crisis. Several of our studies have served as test cases for evaluating Europe’s capacity to respond to health emergencies. Besides, the project is setting up innovative approaches to expedite the evaluation of treatment efficacy, in the context of future epidemic outbreaks, by facilitating data sharing between pandemic trials.
Before 2022, travel-related cases outside Africa were rare, and onward transmission was limited. However, in May 2022, an unprecedented global outbreak led the World Health Organization (WHO) to declare mpox a Public Health Emergency of International Concern (PHEIC). Although cases outside of Africa declined rapidly by the end of summer 2022, cases continue to be reported in previously unaffected regions (i.e. South America, Europe), signaling a potential shift from an epidemic outbreak to an endemic worldwide presence of the virus. In Africa, the Democratic Republic of Congo (DRC) and neighboring countries continue to face a concerning number of cases, along with the emergence of a new clade. This situation prompted the WHO to re-declare mpox a PHEIC in August 2024. Continuous surveillance remains crucial.
The MPX-RESPONSE project aims to deepen our understanding of mpox, including its transmission patterns, and the evolution of the disease (MOSAIC cohort; WP2). The project will also assess the efficacy and safety of antiviral treatments through randomized clinical trials in three different regions of the world (UNITY, EPOXI and MOSA). Therefore, another important project’s outcome will be the validation (or not) of existing antiviral treatments for the mpox indication (WP3; WP4).
Finally, the project will contribute to enhance Europe’s preparedness for future health crisis. Several of our studies have served as test cases for evaluating Europe’s capacity to respond to health emergencies. Besides, the project is setting up innovative approaches to expedite the evaluation of treatment efficacy, in the context of future epidemic outbreaks, by facilitating data sharing between pandemic trials.
The MOSAIC cohort (WP2) provides comprehensive insights into the clinical and virological characteristics of mpox caused by the clade IIb variant. The study underscores the need for continued research and forms the basis of a clinical characterization protocol for the new ongoing mpox outbreaks. To date, the work has involved establishing the cohort in four European Community countries (France, Italy, Spain and Belgium), as well as analyzing data from the entire cohort (Europe , UK, and Switzerland) and analyzing samples collected in France between July 2022 and the end of follow-up in January 2024.
EPOXI (WP3) is a RCT that aims at assessing the efficacy and safety of tecovirimat SIGA, against mpox. The goal is to secure marketing authorization from the EMA, if the treatment demonstrates positive results. Ethical authorizations to start the study in eight European countries has been secured in June 2024, and inclusion of mpox patients hast begun.
UNITY and MOSA (WP4) are two RTCs aims at assessing the efficacy and safety of existing antivirals, in different regions of the world. While UNITY focuses on Brazil, Argentina and Switzerland; MOSA is concentrating on Africa. In RP2, efforts have been made to establish and maintain the operational components of the UNITY trial, including data management, statistics and pharmacovigilance performed by the French ANRS MIE agency. In August 2024, UNITY is now almost halfway to reaching its recruitment target. Additionally, work has been done on facilitating data sharing both within the MPX-RESPONSE project, and with external trials. By the end of the period, the operational aspects of the MOSA trial have also been set up.
EPOXI (WP3) is a RCT that aims at assessing the efficacy and safety of tecovirimat SIGA, against mpox. The goal is to secure marketing authorization from the EMA, if the treatment demonstrates positive results. Ethical authorizations to start the study in eight European countries has been secured in June 2024, and inclusion of mpox patients hast begun.
UNITY and MOSA (WP4) are two RTCs aims at assessing the efficacy and safety of existing antivirals, in different regions of the world. While UNITY focuses on Brazil, Argentina and Switzerland; MOSA is concentrating on Africa. In RP2, efforts have been made to establish and maintain the operational components of the UNITY trial, including data management, statistics and pharmacovigilance performed by the French ANRS MIE agency. In August 2024, UNITY is now almost halfway to reaching its recruitment target. Additionally, work has been done on facilitating data sharing both within the MPX-RESPONSE project, and with external trials. By the end of the period, the operational aspects of the MOSA trial have also been set up.
MOSAIC offers important lessons for the clinical research community in terms of observational data collection and helped the consortium to adapt its standardized tools for the rapid and harmonized collection of data and biological samples that are made freely available and can now be applied to new ongoing Public Health Emergency of International Concern (PHEIC).
EPOXI is a test case for pandemic preparedness in the EU and globally. It will provide insight into the opportunities and bottlenecks of mounting a rapid scientific response to new outbreaks, and the possibilities for data sharing between pandemic trials. Furthermore, it will explore in-depth virological diagnostics by full sequencing of viral isolates and follow-up of immunological response in patient samples.
WP4: No results have yet been disseminated, since the UNITY trial has not yet finalized recruitment.
EPOXI is a test case for pandemic preparedness in the EU and globally. It will provide insight into the opportunities and bottlenecks of mounting a rapid scientific response to new outbreaks, and the possibilities for data sharing between pandemic trials. Furthermore, it will explore in-depth virological diagnostics by full sequencing of viral isolates and follow-up of immunological response in patient samples.
WP4: No results have yet been disseminated, since the UNITY trial has not yet finalized recruitment.