Clinical trial NCT05940545: UMIT-1 Trial Favipiravir & Ribavirin for the Treatment of CCHF
Official title: UMIT-1 Trial: Favipiravir & Ribavirin Phase IB A Randomised Phase Ib Study to Determine the Phase II Dose and to Evaluate the Safety and Efficacy of Intravenous (IV) Favipiravir & Ribavirin
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: CCHF
Lead sponsor: Liverpool School of Tropical Medicine
Sponsor class: OTHER
First posted: 2023-07-11
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Adult in-patients (≥18 years) with laboratory confirmed CCHF infection by positive polymerase chain reaction (PCR) test.
2. Ability to provide informed consent signed by study patient or legally acceptable representative
3. 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 section 5.4 below) from the first administration of trial treatment, throughout trial treatment and for the duration outlined in trial protocol as well as addition 14 days for women and 7 days for men after the last dose of trial treatment.
4. Severity Grading System (SGS) for CCHF - mild/moderate.
5. Less than or equal to 7 days from onset of CCHF symptoms

Exclusion Criteria:

1. Stage 4 severe chronic kidney disease or requiring dialysis (i.e., estimated glomerular filtration (eGFR) rate \<30 mL/min/1.73 m2)
2. Pregnant or breast feeding
3. Anticipated transfer to another hospital which is not a study site within 72 hours
4. Known Allergy to any study medication
5. Patients participating in another clinical trial of an investigational medicinal product (CTIMP) within the last 30 days.
6. Positive COVID-19 PCR
7. Previous intolerance of Favipiravir or Ribavirin
8. Haemoglobinopathies
9. Unstable cardiac diseases within 6 months
10. Any participants deemed not suitable, based on investigators opinion.
11. Patients taking the drugs listed in section 8.11 within 30 days or 5 times the half-life (whichever is longer) of enrolment

Primary outcomes:
measure: Safety objective To determine the safety and tolerability of multiple doses of IV Favipiravir in patients with CCHF
timeFrame: Up to day 8
measure: To determine the safety and tolerability of multiple doses of IV Favipiravir in combination with Ribavirin in patients with CCHF
timeFrame: up to day 8
Secondary outcomes:
measure: Pharmacokinetic objective: To characterise the plasma pharmacokinetics of multiple doses of IV Favipiravir and IV Favipiravir in combination with Ribavirin
timeFrame: up to Day 8
measure: Virologic objective
timeFrame: Change from baseline over time, up to Day 29, in viral load
measure: Clinical objective
timeFrame: Mortality at Days 15 and 29
measure: Clinical objective
timeFrame: Time from randomisation to death (up to day 29)
Other outcomes:
measure: Pharmacokinetic objective: To investigate the exposure-response relationship of IV Favipiravir on CCHF viral dynamics.
timeFrame: At End of study (6 Months)
measure: Pharmacokinetic objective: To investigate the exposure-response relationship of IV Favipiravir on CCHF viral dynamics.
timeFrame: At End of study (6 Months)
measure: Pharmacokinetic objective: To characterise virus and host immune response.
timeFrame: At End of study (6 Months)
measure: Pharmacokinetic objective: To characterise virus and host immune response.
timeFrame: At End of study (6 Months)
measure: Measure immune response by aldehyde oxidase (AO) / xanthine oxidase (XO) activity.
timeFrame: At End of study (6 Months)
Locations:
city: Ankara
country: Turkey
facility: Ankara Oncology Training and Research Center
state: Yenimahalle
Study officials:
affiliation: Liverpool School of Tropical Medicine
name: Lucy E Read, PhD, MRCP
role: STUDY_DIRECTOR
References: