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
Adult in-patients (≥18 years) at the time of screening.
Confirmed CCHF infection: Laboratory confirmed CCHF infection defined as positive polymerase chain reaction (PCR) test within 5 days prior to randomisation.
Ability to provide informed consent signed by study patient or legally acceptable representative (for illiterate individuals).
Women of childbearing potential (WOCBP) and male patients who are sexually active with WOCBP must agree to use a highly effective method of contraception (as outlined in Protocol section 5.4) from the first administration of trial treatment, throughout trial treatment and for the duration outlined.
Severe renal impairment: Stage 4 severe chronic kidney disease or requiring dialysis (i.e., estimated glomerular filtration (eGFR) rate <30 mL/min/1.73 m²).
Pregnant or breast feeding.
Anticipated transfer to another hospital which is not a study site within 72 hours.
Known Allergy to any study medication.
Parallel
Favipiravir
Drug6-fluoro-3-hydroxypyrazine-2-carboxamide, T-705
Ribavin
Drug1-3,4-dihydroxy-5-1,2,4-triazole-3-carboxamide
Optimised Standard of Care
Other interventionOptimised 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.
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)
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
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
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
To characterise virus, host immune response and viral resistance over time
Change in host immune response, CCHFV culture and sequencing related to study agent administration
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Liverpool School of Tropical Medicine
Lead sponsor
MEDEX
Collaborator
Medical Research Council
Collaborator
