The classic website will no longer be available as of June 25, 2024. Please use the modernized ClinicalTrials.gov.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05940545
Recruitment Status : Recruiting
First Posted : July 11, 2023
Last Update Posted : October 5, 2023
Sponsor:
Information provided by (Responsible Party):
Liverpool School of Tropical Medicine

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated 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
Actual Study Start Date : July 12, 2023
Estimated Primary Completion Date : September 30, 2023
Estimated Study Completion Date : December 31, 2023

Resource links provided by the National Library of Medicine

Drug Information available for: Ribavirin

Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Safety objective To determine the safety and tolerability of multiple doses of IV Favipiravir in patients with CCHF [ Time Frame: 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)


  2. To determine the safety and tolerability of multiple doses of IV Favipiravir in combination with Ribavirin in patients with CCHF [ Time Frame: 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 :
  1. Pharmacokinetic objective: To characterise the plasma pharmacokinetics of multiple doses of IV Favipiravir and IV Favipiravir in combination with Ribavirin [ Time Frame: 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.


  2. Virologic objective [ Time Frame: 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

  3. Clinical objective [ Time Frame: 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.

  4. Clinical objective [ Time Frame: 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:
  1. Pharmacokinetic objective: To investigate the exposure-response relationship of IV Favipiravir on CCHF viral dynamics. [ Time Frame: At End of study (6 Months) ]
    Change in host immune response

  2. Pharmacokinetic objective: To investigate the exposure-response relationship of IV Favipiravir on CCHF viral dynamics. [ Time Frame: At End of study (6 Months) ]
    Change in CCHFV culture and sequencing

  3. Pharmacokinetic objective: To characterise virus and host immune response. [ Time Frame: At End of study (6 Months) ]
    Change in host immune response

  4. Pharmacokinetic objective: To characterise virus and host immune response. [ Time Frame: At End of study (6 Months) ]
    Change in CCHFV culture and sequencing

  5. Measure immune response by aldehyde oxidase (AO) / xanthine oxidase (XO) activity. [ Time Frame: 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
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05940545


Contacts
Layout table for location contacts
Contact: Lucy Read +447743438383 lucy.read@lstmed.ac.uk
Contact: Umit-1 Study umit@lstmed.ac.uk

Locations
Layout table for location information
Turkey
Ankara Oncology Training and Research Center Recruiting
Ankara, Yenimahalle, Turkey, 06200
Contact: Mustafa Ertek       ertekmustafa@hotmail.com   
Contact: Mehmet Yildiz       mehmet.yildiz@medex-smo.com   
Sponsors and Collaborators
Liverpool School of Tropical Medicine
Investigators
Layout table for investigator information
Study Director: Lucy E Read, PhD, MRCP Liverpool School of Tropical Medicine
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Layout table for additonal information
Responsible Party: Liverpool School of Tropical Medicine
ClinicalTrials.gov Identifier: NCT05940545    
Other Study ID Numbers: 22-021
First Posted: July 11, 2023    Key Record Dates
Last Update Posted: October 5, 2023
Last Verified: June 2023

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Ribavirin
Favipiravir
Antimetabolites
 Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents