NCT04907682

Brief Summary

This exploratory, prospective, controlled, multisite, open label, randomized clinical trial with two treatment arms aims to compare favipiravir, a new treatment candidate for Lassa fever (LF), with the current standard of care, ribavirin. The primary endpoints of this research are (1) the description of classical pharmacokinetic parameters of favipiravir in comparison with ribavirin standard treatment in patients suffering from LF and (2) the safety and tolerability of both study drugs in the investigated regimens.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
40

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Jul 2021

Shorter than P25 for phase_2

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 6, 2021

Completed
26 days until next milestone

First Posted

Study publicly available on registry

June 1, 2021

Completed
2 months until next milestone

Study Start

First participant enrolled

July 30, 2021

Completed
1.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 10, 2022

Completed
7 days until next milestone

Study Completion

Last participant's last visit for all outcomes

November 17, 2022

Completed
Last Updated

February 8, 2023

Status Verified

November 1, 2022

Enrollment Period

1.3 years

First QC Date

May 6, 2021

Last Update Submit

February 7, 2023

Conditions

Keywords

RibavirinFavipiravirviral hemorrhagic fever

Outcome Measures

Primary Outcomes (5)

  • Pharmacokinetic parameter of favipiravir: Maximum plasma concentration (Cmax)

    Maximum plasma concentration (Cmax) of favipiravir

    Day 1, Day 2, Day 4, Day 6, Day 7, Day 8 and Day 10 of the study conduct

  • Pharmacokinetic parameter of favipiravir: Time to maximum concentration (Tmax)

    Time to maximum concentration (Tmax) of favipiravir

    Day 1, Day 2, Day 4, Day 6, Day 7, Day 8 and Day 10 of the study conduct

  • Pharmacokinetic parameter of favipiravir: Area under the concentration-time curve (AUC)

    Area under the concentration-time curve (AUC) of favipiravir

    Day 1, Day 2, Day 4, Day 6, Day 7, Day 8 and Day 10 of the study conduct

  • Pharmacokinetic parameter of favipiravir: Half life (T1/2)

    Half life (T1/2) of favipiravir

    Day 1, Day 2, Day 4, Day 6, Day 7, Day 8 and Day 10 of the study conduct

  • Proportion of drug related AEs and SAEs of both study treatments

    Safety and tolerability of ribavirin and favipiravir in investigated regimens by investigating the proportion of drug related AEs and SAEs

    throughout study completion (10 days per participant)

Secondary Outcomes (7)

  • Mutagenicity

    10 days

  • Change from baseline in Viral RNA loads

    Day of enrollment - Day 10

  • Change from baseline in Lassa virus titers

    Day of enrollment - Day 10

  • Change from baseline in Lassa virus serological status

    10 days

  • Pharmacokinetic (PK) modelling and simulations

    Day 1, Day 2, Day 4, Day 6, Day 7, Day 8 and Day 10 of the study conduct

  • +2 more secondary outcomes

Study Arms (2)

Intravenous ribavirin

ACTIVE COMPARATOR

standard treatment: Irrua regimen * 100 mg/kg Day 1 (dose is divided: 2/3 stat, 1/3 8 hours later, maximum dose is 7g/day) * 25 mg/kg days 2-7 * 12.5 mg/kg days 8-10

Drug: Ribavirin iv

Oral favipiravir

EXPERIMENTAL

Oral favipiravir * Day 1 2400mg(H0)-2400mg(H8)-1200mg(H16) * Day 2-10 1200mg twice daily (BD)

Drug: Favipiravir

Interventions

100 mg/kg Day 1 (dose is divided: 2/3 stat, 1/3 8 hours later, maximum dose is 7g/day), then 25 mg/kg days 2-7, 12.5 mg/kg days 8-10

Also known as: Irrua regimen
Intravenous ribavirin

Day 1 2400mg(H0)-2400mg(H8)-1200mg(H16), Day 2-10 1200mg twice daily

Also known as: Avigan
Oral favipiravir

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age ≥ 18 years
  • LF confirmed by RT-PCR (reverse-transcription polymerase chain reaction)
  • Written informed consent

You may not qualify if:

  • Inability to give consent (e.g. unconscious patients/ cognitively impaired patients)
  • Pregnancy/lactation (evidenced by negative urine pregnancy test in women of child-bearing potential)
  • Women who plan to get pregnant within the upcoming 6 months
  • Severe malnutrition (BMI\<16)
  • Known intolerance to ribavirin or favipiravir
  • History of hemoglobinopathies (i.e., sickle-cell anaemia or thalassemia major) and/or haemophilia
  • Organ failure as evidenced by:
  • Creatinine ≥ 3x upper limit of normal (ULN)
  • Aspartate aminotransferase (AST/GOT) \> 150 IU/l
  • Alert, confusion, voice, pain, unresponsive (ACVPU) score = V or P or U (corresponds to Glasgow Coma Scale (GCS) ≤ 12)
  • Severe central nervous system features (e.g. seizures, restlessness, confusion and coma)
  • O2 Saturation \< 90%
  • Hematocrit \<30 %
  • Severe anaemia requiring blood transfusion
  • Inability to take oral drug (e.g. encephalopathy, severe vomiting)
  • +1 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Irrua Specialist Teaching Hospital

Irrua, Edo, Nigeria

Location

Federal Medical Center of Owo

Owo, Ondo State, Nigeria

Location

MeSH Terms

Conditions

Lassa FeverHemorrhagic Fevers, Viral

Interventions

favipiravir

Condition Hierarchy (Ancestors)

Arenaviridae InfectionsRNA Virus InfectionsVirus DiseasesInfections

Study Officials

  • Peter Akhideno, Dr

    ISTH

    PRINCIPAL INVESTIGATOR
  • Sylvanus Okogbenin, Prof

    ISTH

    PRINCIPAL INVESTIGATOR
  • Oluwafemi Ayodeji, Dr

    FMCO

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: Exploratory, prospective, controlled, multisite, open label, randomized clinical trial with two arms
Sponsor Type
OTHER GOV
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 6, 2021

First Posted

June 1, 2021

Study Start

July 30, 2021

Primary Completion

November 10, 2022

Study Completion

November 17, 2022

Last Updated

February 8, 2023

Record last verified: 2022-11

Data Sharing

IPD Sharing
Will share

In line with the funding conditions, individual participant data (IPD) is to be shared. However, this will be de-identified IPD that used to generate the results reported (text, tables, figures and appendices). IPD sharing will begin after publication of primary results and will be available for a period which is aligned with the data sharing agreements approved by the research ethics committees of the counties/sites participating in the trial. The IPD shall be made available via a request and evaluation process to investigators whose proposed research has received IRB approval. All investigators to whom this IPD is made available will be required to be part of the execution of a data use agreement.

Shared Documents
STUDY PROTOCOL, ICF, CSR
Time Frame
From the time of publication and for a period which is aligned with the data sharing agreements approved by the research ethics committees of the counties/sites participating in the trial.
Access Criteria
This IPD shall be made available via a request and evaluation process to investigators whose proposed research has received inistitutional review board (IRB) approval. All investigators to whom this IPD is made available will be required to be part of the execution of a data use agreement. The data shall be made available through a governed data access process which includes a transparent, accountability and decision-making process: Completion of data request form Evaluation by a data access committee Data sharing Agreement Secure transfer of data

Locations