UMIT-2 A randomized controlled adaptive multi-arm platform trial for patients with CCHF
Lead Research Organisation:
Liverpool School of Tropical Medicine
Department Name: Clinical Sciences
Abstract
Viral Haemorrhagic fevers (VHFs) are life-threatening acute viral infections that can spread from person-to-person. They often have high case fatality rates (CFR) but severely limited treatment options. Crimean-Congo Haemorrhagic Fever (CCHF) is a VHF and major emerging infectious diseases threat, with Turkiye and Iraq currently the epicentres of worldwide activity. At present, CCHF case management relies on the provision of optimised supportive care with antiviral treatment options lacking a robust evidence base. As VHFs generally emerge in under-resourced regions, funding for CCHF research has been neglected and economic incentives to invest in such research are not readily apparent. Recognising CCHF's wide and expanding geographical distribution, together with the lack of treatment options or vaccines, WHO has designated CCHFV one of the ten high-priority pathogens identified in the WHO R&D Blueprint for Action to Prevent Epidemics.
The UMIT-2 Trial (UMIT = 'Hope' in Turkish) will be the first large randomised controlled evaluation of novel therapeutics in CCHF, undertaken in multiple trial sites in Turkiye and Iraq. It uses an efficient adaptive platform design (Phase IIb), focussed on antiviral efficacy with interim monitoring to introduce new arms and will allow early stopping for futility, efficacy, or safety. UMIT-2 will provide key efficacy data, including generating a Bayesian probability of study success (POSS) for arms in later Phase III trials. The primary endpoint, design and power calculations for UMIT-2 are based on the ability of therapeutics to demonstrate improved CCHFV viral load reduction and clearance compared to standard of care. CCHFV viral load has been consistently shown to be the most important prognostic indicator of outcome (in accordance with other VHFs), with severe/fatal cases having higher and more prolonged duration of viraemia.
The UMIT-2 team provide world-class expertise in designing and running platform trials, particularly in anti-viral therapeutics and pandemic responses. We are committed to delivering practical solutions to global health challenges and inequities including neglected priority diseases such as CCHF. We undertake high-quality global research, which is diverse, promotes multi-disciplinarity and strengthens global health security research capacity. International collaborations with LMICs are essential to develop capacity in addressing global health challenges such as VHFs. We are committed to developing long-term equitable partnerships with a clearly defined shared leadership approach across the UMIT partners. The clear translational aims of UMIT-2, combined with research outcomes that are patient-centred and achievable, will enable a strong partnership to develop and drive the group to equitable success.
The UMIT-2 Trial (UMIT = 'Hope' in Turkish) will be the first large randomised controlled evaluation of novel therapeutics in CCHF, undertaken in multiple trial sites in Turkiye and Iraq. It uses an efficient adaptive platform design (Phase IIb), focussed on antiviral efficacy with interim monitoring to introduce new arms and will allow early stopping for futility, efficacy, or safety. UMIT-2 will provide key efficacy data, including generating a Bayesian probability of study success (POSS) for arms in later Phase III trials. The primary endpoint, design and power calculations for UMIT-2 are based on the ability of therapeutics to demonstrate improved CCHFV viral load reduction and clearance compared to standard of care. CCHFV viral load has been consistently shown to be the most important prognostic indicator of outcome (in accordance with other VHFs), with severe/fatal cases having higher and more prolonged duration of viraemia.
The UMIT-2 team provide world-class expertise in designing and running platform trials, particularly in anti-viral therapeutics and pandemic responses. We are committed to delivering practical solutions to global health challenges and inequities including neglected priority diseases such as CCHF. We undertake high-quality global research, which is diverse, promotes multi-disciplinarity and strengthens global health security research capacity. International collaborations with LMICs are essential to develop capacity in addressing global health challenges such as VHFs. We are committed to developing long-term equitable partnerships with a clearly defined shared leadership approach across the UMIT partners. The clear translational aims of UMIT-2, combined with research outcomes that are patient-centred and achievable, will enable a strong partnership to develop and drive the group to equitable success.
