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Lassa FeverPhase 2SAFARINCT04907682

Pharmacokinetics, Tolerability and Safety of Favipiravir Compared to Ribavirin for the Treatment of Lassa Fever

A Phase 2 study testing Ribavirin iv and Favipiravir in people with Lassa Fever, run by Bernhard Nocht Institute for Tropical Medicine at 2 sites in Nigeria.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Lassa Fever
What is being tested?
Ribavirin iv and Favipiravir
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
2 sitesNigeria
Study dates
30 Jul 2021to 17 Nov 2022
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

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

Who cannot join

  • 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
Show all 16Show fewer
  • 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)
  • Patients who already received ribavirin or favipiravir within the preceding 7 days

Trial locations and contacts

2 sites in 1 country.

Nigeria2 sites

  • Irrua Specialist Teaching Hospital

    Irrua, Edo

  • Federal Medical Center of Owo

    Owo, Ondo State

Other trials in Nigeria

About this study

Official title: Pharmacokinetics, Tolerability and Safety of Favipiravir Compared to Ribavirin for the Treatment of Lassa Fever: A Randomized Controlled Open Label Phase II Clinical Trial

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.

Read the detailed description

The currently used antiviral for the treatment of LF, which is also recommended by the World Health Organization (WHO) and the Nigeria Center for Disease Control, is ribavirin. However, evidence for ribavirin efficacy in LF patients adds up to the results of a single study with serious limitations. A promising new treatment candidate that showed efficacy against LF in preclinical studies is Favipiravir. It has further been evaluated for the treatment of Ebola Virus disease during the West-African Ebola outbreak and is approved for treatment of pandemic influenza virus infections in Japan.

The study will be conducted at two study sites in Nigeria: the Irrua Specialist Teaching Hospital (ISTH) and the Federal Medical Center of Owo (FMCO). Lassa fever patients of 18 years and older with LF confirmed by reverse-transcription polymerase chain reaction (RT-PCR) hospitalized at either ISTH or FMCO will be asked to participate in this study. A total of 40 evaluable participants will be randomized to two treatment arms (20 participants per arm): intravenous ribavirin standard of care treatment (Irrua regimen), oral favipiravir. Patients will be included in the study after giving written informed consent and if all inclusion criteria and no exclusion criteria are met. Multiple blood draws with the purpose of virologic, serologic and immunological analyses, hematological and biochemical analyses as well as pharmacokinetic analyses will be performed throughout the study duration of ten days. Adverse events (AEs), serious adverse events (SAEs) and pregnancy will be captured, monitored and followed-up. A medical monitor will be available for study investigators to assist with any clinical and safety related questions. An external data safety monitoring board (DSMB) will conduct periodic safety reviews.

Data will be captured on source documents and electronic case report forms (eCRFs). Informed consent forms will be stored in a lockable cabinet. Participants data will only be linked to the unique identifier to ensure pseudonymity.

Statistical analysis of study endpoints and pharmacokinetic parameters will be performed descriptively. Missing data will be treated as such, no imputation will be applied.

The study will be conducted in compliance with the protocol, the Declaration of Helsinki, the International Conference on Harmonisation-Good Clinical Practice (ICH-GCP) guideline and the Nigerian National Code for Health Research Ethics, in particular concerning the submission to the ethics committees and the protection of personal data as well as other national and regulatory requirements.

Conditions
Lassa Fever
Being tested
Ribavirin iv, Favipiravir
Keywords
Ribavirin, Favipiravir, viral hemorrhagic fever
Medical subject headings
Lassa Fever, Hemorrhagic Fevers, Viral

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Ribavirin ivDrug

    Also called Irrua regimen

    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

  • FavipiravirDrug

    Also called Avigan

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

Study groups in NCT04907682
Study groupRoleWhat they receive
Intravenous ribavirinActive comparatorstandard 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
Receives: Drug: Ribavirin iv
Oral favipiravirExperimentalOral favipiravir * Day 1 2400mg(H0)-2400mg(H8)-1200mg(H16) * Day 2-10 1200mg twice daily (BD)
Receives: Drug: Favipiravir

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Pharmacokinetic parameter of favipiravir: Maximum plasma concentration (Cmax)

    Maximum plasma concentration (Cmax) of favipiravir

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

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

    Time to maximum concentration (Tmax) of favipiravir

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

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

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

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

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

    Half life (T1/2) of favipiravir

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

  5. 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

    Measured: throughout study completion (10 days per participant)

Secondary outcomes (7)

  1. Mutagenicity

    Mutagenicity of ribavirin and favipiravir measured via nucleotide exchange rate in individual Lassa virus genomes

    Measured: 10 days

  2. Change from baseline in Viral RNA loads

    Description of viral loads during treatment Relative Lassa virus RNA concentrations in RNA copies per milliliters (RNA copies/ml).

    Measured: Day of enrollment - Day 10

  3. Change from baseline in Lassa virus titers

    Description of infectious titers during treatment. Infectious titers expressed as focus forming units per milliliters or FFU/ml using immuno-focus assay for Lassa virus.

    Measured: Day of enrollment - Day 10

  4. Change from baseline in Lassa virus serological status

    Description of antibody response during treatment. To evaluate the presence or absence of Lassa virus immunoglobulin M (IgM) and G (IgG) antibodies; qualitative results

    Measured: 10 days

  5. Pharmacokinetic (PK) modelling and simulations

    Dosing regimen (mg/frequency/day) resulting in optimal PK/PD target attainment

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

  6. Correlation between drug exposure and different parameters

    Correlation between drug exposure (AUC, Cl/F) and i. Viral elimination dynamics (elimination rate constant), including time to viral clearance (time to negative RT-PCR blood for Lassa virus), regression analysis of viral loads in function of time ii. Length of hospital stay: duration of hospitalization as defined by the enrollment date to discharged data iii. Number of deaths: mortality records iv. Blood component therapy use as concomittant medication

    Measured: 10 days

  7. Co-variates impacting on drug exposure

    Co-variates impacting on drug exposure: demographices, biological, clinical and virologic data captured in patient case files and sources documents may be assessed as convariates on drug exposure

    Measured: 10 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Jun 2021
  2. Study start30 Jul 2021
  3. Primary completion10 Nov 2022
  4. Study completion17 Nov 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Exploratory, prospective, controlled, multisite, open label, randomized clinical trial with two arms
Masking
None (open label)
Enrolment
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04907682
Sponsor's protocol ID
SAFARI
Other IDs
PACTR202010817169062
Acronym
SAFARI
Status last verified
Nov 2022
First submitted
6 May 2021
Last updated
8 Feb 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: 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.

Publications

  • Erameh C, Okwaraeke K, Kleist C, Edeawe O, Adedosu N, Ekata E, Abejegah C, Owhin S, Babatunde F, Omansen T, Meneguim A, Duvignaud A, Mischlinger J, Ithete N, Oestereich L, Hinzmann J, Ahmed L, Duraffour S, Eifedyi R, Okogbenin S, Akhideno P, Ayodeji OO, Gunther S, Wicha SG, Jaspard M, Pahlmann M, Ramharter M, Groger M. Favipiravir for Lassa fever: an open-label, randomized controlled phase 2 trial. Nat Med. 2026 Jul;32(7):2522-2532. doi: 10.1038/s41591-026-04402-w. Epub 2026 May 15.

    PubMed 42141199

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ribavirin iv and Favipiravir in people with Lassa Fever, run by Bernhard Nocht Institute for Tropical Medicine at 2 sites in Nigeria.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Nigeria. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pharmacokinetic parameter of favipiravir: Maximum plasma concentration (Cmax) (time frame: Day 1, Day 2, Day 4, Day 6, Day 7, Day 8 and Day 10 of the study conduct). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04907682, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Feb 2023.

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