UMIT-1 Trial Favipiravir & Ribavirin for the Treatment of CCHF

Sponsor

Liverpool School of Tropical Medicine (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05940545

Collaborator

(none)

Enrollment

Arms

5.4

Anticipated Duration (Months)

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
CCHF	Drug: Favipiravir Drug: Ribavirin	Phase 1/Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

24 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Jul 20, 2023

Anticipated Primary Completion Date :

Sep 30, 2023

Anticipated Study Completion Date :

Dec 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Cohort 1 6 patients will be randomised to starting dose of favipiravir 1800 mg BD (day 1), then 800mg BD Day 2 to 10, or standard of care.	Drug: Favipiravir Small molecule antiviral
Active Comparator: Cohort 2 6 patients will be randomised to starting dose of favipiravir 2600 mg BD (day 1), then 1200mg BD day 2 to 10, or standard of care.	Drug: Favipiravir Small molecule antiviral
Active Comparator: Cohort 3 6 patients will be randomised to starting dose of favipiravir 1800 mg BD (day 1), then 800mg BD Day 2 to 10 plus Ribavirin, or standard of care.	Drug: Favipiravir Small molecule antiviral Drug: Ribavirin Small molecule antiviral
Active Comparator: Cohort 4 6 patients will be randomised to starting dose of favipiravir 2600mg BD (day 1), then 1200mg BD day 2 to 10 plus Ribavirin, or standard of care.	Drug: Favipiravir Small molecule antiviral Drug: Ribavirin Small molecule antiviral

Outcome Measures

Primary Outcome Measures

Safety objective To determine the safety and tolerability of multiple doses of IV Favipiravir in patients with CCHF [Up to day 8]
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)
To determine the safety and tolerability of multiple doses of IV Favipiravir in combination with Ribavirin in patients with CCHF [up to day 8]
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)

Secondary Outcome Measures

Pharmacokinetic objective: To characterise the plasma pharmacokinetics of multiple doses of IV Favipiravir and IV Favipiravir in combination with Ribavirin [up to Day 8]
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.
Virologic objective [Change from baseline over time, up to Day 29, in viral load]
To investigate the effect of IV Favipiravir alone and in combination with Ribavirin on CCHF viral load
Clinical objective [Mortality at Days 15 and 29]
To investigate the ability of IV Favipiravir and in combination with Ribavirin to reduce the duration of signs and symptoms of CCHF in-patients.
Clinical objective [Time from randomisation to death (up to day 29)]
To investigate the ability of IV Favipiravir and in combination with Ribavirin to reduce the duration of signs and symptoms of CCHF in-patients.

Other Outcome Measures

Pharmacokinetic objective: To investigate the exposure-response relationship of IV Favipiravir on CCHF viral dynamics. [At End of study (6 Months)]
Change in host immune response
Pharmacokinetic objective: To investigate the exposure-response relationship of IV Favipiravir on CCHF viral dynamics. [At End of study (6 Months)]
Change in CCHFV culture and sequencing
Pharmacokinetic objective: To characterise virus and host immune response. [At End of study (6 Months)]
Change in host immune response
Pharmacokinetic objective: To characterise virus and host immune response. [At End of study (6 Months)]
Change in CCHFV culture and sequencing
Measure immune response by aldehyde oxidase (AO) / xanthine oxidase (XO) activity. [At End of study (6 Months)]
To investigate the exposure-response relationship of IV Favipiravir and IV Favirpiravir/Ribavirin on CCHF viral dynamics (Favipiravir inhibits AO and XO is partially involved in metabolism of favipiravir)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Adult in-patients (≥18 years) with laboratory confirmed CCHF infection by positive polymerase chain reaction (PCR) test.
Ability to provide informed consent signed by study patient or legally acceptable representative
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.
Severity Grading System (SGS) for CCHF - mild/moderate.
Less than or equal to 7 days from onset of CCHF symptoms

Exclusion Criteria:

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
Patients participating in another clinical trial of an investigational medicinal product (CTIMP) within the last 30 days.
Positive COVID-19 PCR
Previous intolerance of Favipiravir or Ribavirin
Haemoglobinopathies
Unstable cardiac diseases within 6 months
Any participants deemed not suitable, based on investigators opinion.
Patients taking the drugs listed in section 8.11 within 30 days or 5 times the half-life (whichever is longer) of enrolment

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

Liverpool School of Tropical Medicine

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Liverpool School of Tropical Medicine

ClinicalTrials.gov Identifier:

NCT05940545

Other Study ID Numbers:

22-021

First Posted:

Jul 11, 2023

Last Update Posted:

Jul 11, 2023

Last Verified:

Jun 1, 2023

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Additional relevant MeSH terms:

Ribavirin

Favipiravir

Study Results

No Results Posted as of Jul 11, 2023