UMIT-2 - Adaptive Phase IIb Platform Trial to Determine the Efficacy and Safety of Therapeutics for CCHF

NCT06860334 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: 25-013
• Study Type: interventional
• Target: 378
• Locations: 0 countries
• Sites: N/A

Brief Summary

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

Conditions

Crimean-Congo Hemorrhagic Fever

Keywords

CCHF; Favipiravir; Ribavirin; Crimean Congo Hemorrhagic Fever

Outcome Measures

Primary Outcomes (1)

• 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.

  Day 5 from treatment start

Secondary Outcomes (7)

• Safety Objective: To determine the safety and tolerability of investigational therapeutics relative to the control arm

  Day 29

• Clinical Objective: To compare time to successful hospital discharge between participants receiving investigational therapeutics, relative to the control arm

  Day 29

• Antiviral Objective: To evaluate antiviral efficacy of investigational therapeutics (1)

  Day 10

• Antiviral Objective: To evaluate antiviral efficacy of investigational therapeutics (2)

  Day 10

• Safety Objective: To compare the overall mortality in patients with CCHF who receive different investigational therapeutics with those who receive the control arm

  Day 28

Other Outcomes (1)

• To characterise virus, host immune response and viral resistance over time

  Day 29

Study Arms (3)

Optimised standard of care (oSOC)

ACTIVE COMPARATOR

Optimised 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. The standard of care arm will exclude any medicine defined as investigation arms of this study. Any supportive medication or therapies will be recorded on the patient CRFs.

Other: Optimised Standard of Care

Arm B: Favipiravir

ACTIVE COMPARATOR

Day 1 (First 24 hours): IV Favipiravir 2600 mg twice daily (BD) Day 2 (24-48 hours): IV Favipiravir 1200 mg twice daily (BD) Day 3 -7 (Post 48 hours): Oral (PO) Favipiravir 1200 mg twice daily (BD)1 until hospital discharge up to 7 days (14 doses) whichever is soonest. Plus any additional supportive care deemed necessary by the study investigator

Drug: Favipiravir

Arm C: Ribavirin

ACTIVE COMPARATOR

Day 1 (First 24 hours): IV Ribavirin (33mg/kg) loading dose followed by IV Ribavirin 16mg/kg every 6 hours Day 2 (24-48 hours): IV Ribavirin 16mg/kg four times daily (QDS) Days 3-5: Oral (PO) Ribavirin 16mg/kg four times daily (QDS) Days 6 -7: Oral (PO) Ribavirin 8mg/kg four times daily (QDS) until hospital discharge Plus any additional supportive care deemed necessary by the study investigator

Drug: Ribavin

Interventions

Favipiravir DRUG

6-fluoro-3-hydroxypyrazine-2-carboxamide, T-705

Arm B: Favipiravir

Ribavin DRUG

1-3,4-dihydroxy-5-1,2,4-triazole-3-carboxamide

Arm C: Ribavirin

Optimised Standard of Care OTHER

Optimised 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.

Optimised standard of care (oSOC)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult in-patients (≥18 years)
• Laboratory confirmed CCHF infection by positive polymerase chain reaction (PCR) test within 5 days prior to randomisation
• Capacity 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 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
• Willingness to participate in the full protocol
• Requirement to be hospitalised for treatment-

You may not qualify if:

• 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.
• Previous intolerance of Favipiravir or Ribavirin
• Any participants deemed not suitable, based on investigators opinion.
• Patients taking the drugs listed below within 30 days or 5 times the half-life (whichever is longer) of enrolment:
• Pyrazinamide: Pyrazinamide administration with favipiravir examined possible renal urate transporter interactions. Pyrazinamide increased blood uric acid levels 2 to 9 mg/dL over baseline. The addition of favipiravir increased blood uric acid levels 4 to 11 mg/dL over baseline, indicating a moderate additive effect.
• Repaglinide: Favipiravir administration with repaglinide, an anti-diabetic agent that is extensively metabolized by CYP2C8 and CYP3A4, increased repaglinide plasma AUC 30 to 50% due to inhibition of CYP2C8.
• Theophylline: Theophylline administration with favipiravir increases plasma Cmax and AUC of favipiravir through xanthine oxidase (XO) interaction. The primary metabolite of theophylline is known to be metabolized by XO which is partially involved in metabolism of favipiravir.
• Famciclovir, Sulindac: Famciclovir and Sulindac are converted to active metabolite by Aldehyde Oxidase (AO). Favipiravir inhibits AO and decrease the concentration of active metabolite of Famciclovir and Sulindac.
• Paracetamol: Coadministration of paracetamol (650 mg once daily) and favipiravir (1200 mg twice daily or 800 mg twice daily) increased paracetamol Cmax and AUC by 3% and 16% (1200 mg doses) and by 8% and 14% (800 mg doses). In the UMIT-2 trial after screening and randomisation the daily dose of paracetamol in adults should be no more than 3000 mg/day (rather than 4000 mg/day) -

Sponsors & Collaborators

• Liverpool School of Tropical Medicine: lead

MeSH Terms

Conditions

Hemorrhagic Fever, Crimean

Interventions

favipiravir

Condition Hierarchy (Ancestors)

Arbovirus Infections; Vector Borne Diseases; Infections; Tick-Borne Diseases; Virus Diseases; Bunyaviridae Infections; RNA Virus Infections; Hemorrhagic Fevers, Viral

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 1:1:1 randomised open-label phase 2b trial

Study Record Dates

• First Submitted: February 13, 2025
• First Posted: March 6, 2025
• Study Start: July 1, 2025
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): August 31, 2028
• Last Updated: March 6, 2025

Record last verified: 2025-02