Periodic Reporting for period 1 - MPX-RESPONSE (A clinical research network to improve the management of Monkeypox virus disease)
Okres sprawozdawczy: 2022-08-05 do 2023-08-04
The mpox disease is an acute febrile rash illness caused by the mpox virus, and often accompanied by symptoms such as fever, headache or muscle aches. Since the 1970’s-1980’s, the disease is endemic in West or Central Africa, including sporadic outbreaks that usually resulted from contact with wildlife reservoirs, in particular rodents.
Until recently, there had been very few travel-associated cases in non-African countries, with limited onward transmission. In May 2022, an unprecedented number of cases have been simultaneously reported in countries outside of Africa. This outbreak was unique in scale and cases and was declared a public health emergency of international concern by the World Health Organization (WHO) on 23th July 2022. Since October 2022, the number of cases has decreased but the potential of re-emergence of mpox outside endemic Africa exists.
To date, many questions about the mpox disease remain unanswered and particularly concerning the management of patients. The MPX-RESPONSE project aims to increase our knowledge of the mpox virus disease, to improve its therapeutic management and to further inform public health policies and guidelines through four Work Packages (WP).
MPX-RESPONSE will endeavour to:
(i) assess clinical and virological outcomes of Monkeypox patients, in Europe, treated or not with antiviral drugs (MOSAIC study; WP2)
(ii) determine the effect of different treatments and management options on the clinical outcomes of human mpox infection through three sister randomized controlled trials in different geographical regions of the world that will mostly target mild and moderate patients.
The trials will be conducted at the global level (UNITY trial, WP4), at sub-Saharan Africa (MOSA, WP4) and at the European level (EPOXI trial, WP3), first with Tecovirimat, which is currently the most promising antiviral therapy against mpox. In EPOXI, additional pharmacological, immunological and virological outcomes will be collected to fulfil EMA requirements for treatment authorisation.
Finally, the project will make sure that acquired knowledge is integrated into public health policies and guidelines and that adequate messages are shared with the general public and high-risk populations with the help of patients’ representatives and associations (WP1). To accomplish these objectives, MPX-RESPONSE will build on the expertise and networks of multiples partners including ECRAID and EU-RESPONSE and will reinforce and broaden Europe’s capacity to respond rapidly to public health emergencies
Until recently, there had been very few travel-associated cases in non-African countries, with limited onward transmission. In May 2022, an unprecedented number of cases have been simultaneously reported in countries outside of Africa. This outbreak was unique in scale and cases and was declared a public health emergency of international concern by the World Health Organization (WHO) on 23th July 2022. Since October 2022, the number of cases has decreased but the potential of re-emergence of mpox outside endemic Africa exists.
To date, many questions about the mpox disease remain unanswered and particularly concerning the management of patients. The MPX-RESPONSE project aims to increase our knowledge of the mpox virus disease, to improve its therapeutic management and to further inform public health policies and guidelines through four Work Packages (WP).
MPX-RESPONSE will endeavour to:
(i) assess clinical and virological outcomes of Monkeypox patients, in Europe, treated or not with antiviral drugs (MOSAIC study; WP2)
(ii) determine the effect of different treatments and management options on the clinical outcomes of human mpox infection through three sister randomized controlled trials in different geographical regions of the world that will mostly target mild and moderate patients.
The trials will be conducted at the global level (UNITY trial, WP4), at sub-Saharan Africa (MOSA, WP4) and at the European level (EPOXI trial, WP3), first with Tecovirimat, which is currently the most promising antiviral therapy against mpox. In EPOXI, additional pharmacological, immunological and virological outcomes will be collected to fulfil EMA requirements for treatment authorisation.
Finally, the project will make sure that acquired knowledge is integrated into public health policies and guidelines and that adequate messages are shared with the general public and high-risk populations with the help of patients’ representatives and associations (WP1). To accomplish these objectives, MPX-RESPONSE will build on the expertise and networks of multiples partners including ECRAID and EU-RESPONSE and will reinforce and broaden Europe’s capacity to respond rapidly to public health emergencies
WP2: This initial period was devoted to organising and coordinating the MOSAIC cohort, obtaining regulatory authorisations and enrolling patients. To date, the cohort enrolled 620 patients were included in 6 countries (UK, Switzerland, France, Italy, Belgium, Spain).
WP3: A study team was formed at ECRAID and UMCU in July 2022, connecting with the European scientific community and with other international trial initiatives. A study protocol was designed and a submission package compiled was submitted in CTIS, where EPOXI trial was granted conditional approval in seven countries through an expedited review procedure. Funding was applied for and granted, study sites and relevant vendors were selected, and contracting was initiated. Currently a major revision of the protocol is being prepared for submission in CTIS, adapted to the changed epidemiology of mpox.
WP4: The UNITY study governance was set up, including a DSMB common to UNITY, MOSA, and EPOXI. This, in coordination with the active work of study co-sponsors, allowed for the trial to be launched in March 2023. To date, 37 patients have been enrolled in Brazil and two patients in switzerland. The database was set up by Olso University Hospital, and agreements to share data were signed by parties. The eCRF and first version of data management plan were produced. Safety monitoring activities started, safety SOPs and working instructions were produced, and a safety database was setup at ANRS-MIE/Inserm.
MOSA’s investigator meeting was conducted in Senegal with 10 countries to present the project. Protocol, ICF and SOPs were developed and finalized with local experts according to African specificities. Pre-study visits were conducted in Democratic Republic of Congo (DRC) and Cameroon. Submission in DRC was done, AVAREF submission is delayed independently from PANTHER request. Agreement with SIGA for Tecovirimat provision is finalized. Subcontractors were selected and contracted for study management, monitoring and for IMP management.
WP3: A study team was formed at ECRAID and UMCU in July 2022, connecting with the European scientific community and with other international trial initiatives. A study protocol was designed and a submission package compiled was submitted in CTIS, where EPOXI trial was granted conditional approval in seven countries through an expedited review procedure. Funding was applied for and granted, study sites and relevant vendors were selected, and contracting was initiated. Currently a major revision of the protocol is being prepared for submission in CTIS, adapted to the changed epidemiology of mpox.
WP4: The UNITY study governance was set up, including a DSMB common to UNITY, MOSA, and EPOXI. This, in coordination with the active work of study co-sponsors, allowed for the trial to be launched in March 2023. To date, 37 patients have been enrolled in Brazil and two patients in switzerland. The database was set up by Olso University Hospital, and agreements to share data were signed by parties. The eCRF and first version of data management plan were produced. Safety monitoring activities started, safety SOPs and working instructions were produced, and a safety database was setup at ANRS-MIE/Inserm.
MOSA’s investigator meeting was conducted in Senegal with 10 countries to present the project. Protocol, ICF and SOPs were developed and finalized with local experts according to African specificities. Pre-study visits were conducted in Democratic Republic of Congo (DRC) and Cameroon. Submission in DRC was done, AVAREF submission is delayed independently from PANTHER request. Agreement with SIGA for Tecovirimat provision is finalized. Subcontractors were selected and contracted for study management, monitoring and for IMP management.
WP2: The MOSAIC observational study already contributed to provide crucial information to characterise the disease and inform practice in infectious disease outbreaks An interim analysis has been done for the Conference on Retroviruses and Opportunistic Infections (CROI) on 122 first prospective cases (21 Tecovirimat-treated, 101 not treated). The results told that lesions and symptoms resolved within 28 days in most uncomplicated cases. Some patients still had positive virology samples at day 14 (even in plasma) although they no longer had active lesions.
WP3: This project will assist the ECRAID foundation in acquiring relevant experience and developing standard operating procedures concerning the organization and execution of clinical trials in settings of medical emergencies. This will facilitate responses in case of future health emergencies of infectious nature, increasing European readiness.
WP4: N/A
WP3: This project will assist the ECRAID foundation in acquiring relevant experience and developing standard operating procedures concerning the organization and execution of clinical trials in settings of medical emergencies. This will facilitate responses in case of future health emergencies of infectious nature, increasing European readiness.
WP4: N/A