CCHF has a wide geographical distribution with cases mainly occurring in Asia, the Middle East, South-Eastern Europe and Africa. Since its emergence in 2002, Turkiye has been the epicentre of activity worldwide reporting up to more than 1000 cases annually. CCHF case management relies on the provision of optimised supportive care; therapeutic options lack a robust evidence base The UMIT-2 Trial (UMIT = 'Hope' in Turkish) will be the first large randomised controlled trial 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 allow early stopping for futility, efficacy, or safety
This will be a 1:1:1 randomised open-label phase 2b trial of Favipiravir (IV \& PO) and Ribavirin (IV \& PO) vs optimised standard of care in CCHF aimed at evaluating virological efficacy. This is an adaptive multi-arm Phase II platform for patients with CCHF. Key design features are: Treatment arms can be added or removed. Shared standard of care (SoC, control) arm so that a greater proportion of more patients receive experimental therapeutics. Eligibility to randomisation to specific treatment arms is based on treatment specific inclusion/exclusion criteria and all comparisons to SoC are within the same eligibility set and concurrent randomisation. Timing of interim analyses flexible to make use of the seasonality of CCHF to ensure they take place during low recruitment periods.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
378
6-fluoro-3-hydroxypyrazine-2-carboxamide, T-705
1-3,4-dihydroxy-5-1,2,4-triazole-3-carboxamide
Optimised standard of care will include treatment per national guidelines for CCHF case management in Turkiye and Iraq, and any other supportive medication or therapies as required.
Virologic objective: To compare CCHFV viral dynamics of investigational therapeutics relative to the control arm
Comparison of CCHFV viral load clearance by Day 5 for treatment arms compared to Standard of Care arm.
Time frame: Day 5 from treatment start
Safety Objective: To determine the safety and tolerability of investigational therapeutics relative to the control arm
Comparison of incidence of serious adverse events in treatment arms compared to standard of care arm. Comparison of the frequency and characterisation of clinically significant adverse events related to study agent administration (Safety and Tolerability of Favipiravir and Ribavirin CTCAE v5 Grade ≥3 adverse events)
Time frame: Day 29
Clinical Objective: To compare time to successful hospital discharge between participants receiving investigational therapeutics, relative to the control arm
Time from Randomisation to discharge from hospital
Time frame: Day 29
Antiviral Objective: To evaluate antiviral efficacy of investigational therapeutics (1)
Comparison of CCHFV viral load reduction between for treatment arms compared to Standard of Care arm
Time frame: Day 10
Antiviral Objective: To evaluate antiviral efficacy of investigational therapeutics (2)
Comparison of Viral load reduction by PCR test for treatment arms compared to Standard of Care arm
Time frame: Day 10
Safety Objective: To compare the overall mortality in patients with CCHF who receive different investigational therapeutics with those who receive the control arm
Mortality at Days 14 and 28 (time from date of randomisation to death) for treatment arms compared to Standard of Care arm
Time frame: Day 28
Safety Objective: To compare mortality rates among patients whose baseline predictors of disease place them in different categories for disease severity, who receive different investigational therapeutics.
Mortality at Days 14 and 28 (time from date of randomisation to death) in different SGS groups for treatment arms compared to Standard of Care arm
Time frame: Day 28
Pharmacokinetic objective:To characterise the plasma pharmacokinetics (PK) of therapeutics in CCHF
To investigate the exposure-response relationship of Favipiravir on CCHF viral dynamics by analysing concentrations of investigation therapeutics in plasma
Time frame: Day 29
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.