UMIT-1: A Randomised Phase Ib Study to Determine the Phase II dose and to Evaluate the Safety and Efficacy of intravenous (IV) Favipiravir \& Ribavirin for the Treatment of CCHF
This will be a 2:1 randomised open-label phase I trial of IV Favipiravir and IV Favipiravir plus Ribavirin vs optimised standard of care in CCHF. The phase Ib will be carried out to test the safety and tolerability of IV Favipiravir in hospitalised patients. Following review of safety, tolerability and PK data from evaluated phase I doses, an IV Favipiravir doses will be selected to progress to phase II. virological efficacy.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
24
Small molecule antiviral
Small molecule antiviral
Ankara Oncology Training and Research Center
Ankara, Yenimahalle, Turkey (Türkiye)
RECRUITINGSafety objective To determine the safety and tolerability of multiple doses of IV Favipiravir in patients with CCHF
Adverse events and serious adverse events Dose limiting toxicities (Safety and Tolerability of IV Favipiravir and IV Favipiravir/Ribavirin- CTCAE v5 Grade ≥3 adverse events)
Time frame: Up to day 8
To determine the safety and tolerability of multiple doses of IV Favipiravir in combination with Ribavirin in patients with CCHF
Adverse events and serious adverse events Dose limiting toxicities (Safety and Tolerability of IV Favipiravir and IV Favipiravir/Ribavirin- CTCAE v5 Grade ≥3 adverse events)
Time frame: up to day 8
Pharmacokinetic objective: To characterise the plasma pharmacokinetics of multiple doses of IV Favipiravir and IV Favipiravir in combination with Ribavirin
Evaluation of favipiravir in VHFs is limited by the predicted high-pill burden (up to 30 tablets per day) required and uncertainty around dose and PK. Favipiravir injection (IV favipiravir) is a novel formulation of favipiravir for intravenous drip infusion, with Cmax levels 4-fold higher following administration of multiple doses in cynomolgus monkeys compared to oral (Toyama IB). The favipiravir activity is derived from the intracellular ribofuranosyl-5'-triphosphate (RTP) metabolite that has a longer half-life intracellularly than the parent drug in plasma. Therefore, transiently higher Cmax values are expected to translate into sustained higher intracellular RTP concentrations and thus activity.
Time frame: up to Day 8
Virologic objective
To investigate the effect of IV Favipiravir alone and in combination with Ribavirin on CCHF viral load
Time frame: Change from baseline over time, up to Day 29, in viral load
Clinical objective
To investigate the ability of IV Favipiravir and in combination with Ribavirin to reduce the duration of signs and symptoms of CCHF in-patients.
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Time frame: Mortality at Days 15 and 29
Clinical objective
To investigate the ability of IV Favipiravir and in combination with Ribavirin to reduce the duration of signs and symptoms of CCHF in-patients.
Time frame: Time from randomisation to death (up to day 29)