A Phase 2/3 interventional study of Favipiravir and Ribavirin in Lassa Fever, sponsored by Irrua Specialist Teaching Hospital. Recruiting at 4 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-02-04.
Sponsored by Irrua Specialist Teaching Hospital · Phase 2/3, Interventional, and Treatment
Lassa fever (LF) is a viral haemorrhagic fever responsible of 5000 deaths per year in West Africa, with in-hospital mortality at 12%. Transmission to humans occurs mainly via direct or indirect exposure to excreta from the rodent reservoir, mainly made up of Mastomys natalensis . Less frequently, LASV may also be transmitted from human to human and cause nosocomial outbreaks. Ribavirin is the only treatment available with worrying toxicity, questionable efficacy and low access because of its high cost. Consequently, there is an urgent need for new drugs to treat LF patients. The Research and Development (R\&D) Blueprint of the World Health Organization (WHO) has included LF in the list of priority diseases for urgent research and development.
The INTEGRATE consortium is an unprecedented international collaboration on Lassa fever of 15 partners from 10 countries across West Africa, Europe and North America and across several disciplines (epidemiological researchers, social scientists, medical health facility professionals, humanitarian actors, etc.).
The INTEGRATE study is a platform, multinational, multicentre, sequential, seamless phase II-III, controlled, randomised, superiority trial in open-label parallel arms. Three arms will be assessed and compared to the SCD. Its primary objective is to compare the efficacy of each Investigational Medical Product (IMP) to Standard of Care Drug (SCD) to prevent death or organ failure in hospitalized patients with confirmed LF. Secondary objectives will be i) to compare the safety and tolerability of each IMP and SCD, ii) to compare the efficacy of each IMP and SCD on clinical, virological and biological parameters, iii) to describe the pharmacokinetics of each IMP and iv) to develop a pharmacokinetics / pharmacodynamics model for each IMP informing about optimal dosing regimens and dose-response relationship.
Objectives
1.1 Primary objective The primary objective of the trial is to compare the efficacy of each IMP and SCD to prevent death or organ failure in hospitalized participants with confirmed LF.
1.2. Secondary objectives
Design
Sample size:
In the current version of the protocol (if all sub-protocols start at once):
Duration
38 studies on the registry are indexed under Hemorrhagic Fevers, Viral; 6 are open to participants now.
This study's planned enrollment of 1,755 is above the median of 98 across 29 interventional studies indexed under Hemorrhagic Fevers, Viral.
Browse Hemorrhagic Fevers, Viral studies →This is the only study on the registry with Irrua Specialist Teaching Hospital as lead sponsor.
Counted across the registry records on this site, refreshed daily.
General
Inclusion criteria
Exclusion criteria
Sub-protocols
2.1 Favipiravir high dose sub-protocol
Inclusion criteria • Age ≥ 18 years old
Exclusion criteria • Pregnancy (evidenced by positive urine pregnancy test in women of )
2.2. Favipiravir-Ribavirin sub-protocol
Inclusion criteria
Exclusion criteria
2.3. Dexamethasone sub-protocol
Inclusion criteria • Age ≥ 12 years old
Exclusion criteria
2.4 ARN-75039 subprotocols
Exclusion criteria • History of severe gastrointestinal disease
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
QT and QTc
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Excipients
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Oral favipiravir: 2400 mg BID D1; 1600 mg BID D2-D10
Drug: Favipiravir
Intravenous ribavirin (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 single dose days 2-7, 12.5 mg/kg single dose days 8-10).
Drug: Favipiravir
Oral favipiravir: 2400 mg BID D1; 1200 mg BID D2-D10 Intravenous ribavirin (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 single dose days 2-7, 12.5 mg/kg single dose days 8-10).
Drug: Favipiravir · Drug: Ribavirin
IV ribavirin, Irrua regimen IV or oral dexamethasone 6mg/day (For the first 48 hours, dexamethasone will be given intravenously (i. Afterwards, a switch to oral dexamethasone (same dosage) is permitted at the discretion of the study physician.)
Drug: Ribavirin · Drug: Dexamethasone
• ARN-75039 high dose * D1: 300mg (morning), 200mg (evening) * D2: 200mg BID * D3-10: 100mg BID
Drug: ARN-75039 high dose
• ARN-75039 low dose * D1: 150mg (morning), 100mg (evening) * D2: 100mg BID * D3-10: 50mg BID
Drug: ARN-75039 low dose
Interventional Medicinal Product (IMP)
Control arm
Also known as: Standard of care
Interventional Medicinal Product (IMP)
Investigational Medicinal Product
Investigational Medicinal Product
Death
Proportion of participants death definition by Y/N measure Clinical aggravation is defined as the first occurrence of one of the following conditions, at any time point between baseline and Day 14 (included): Death, or Increase (+1 or +2) in the number (0, 1 or 2) of organ failures among: Renal failure: KDIGO stage 3 Respiratory failure: SpO2/FiO2\* ≤ 315 Cardiovascular failure: MBP\*\* \< 65 mmHg or SBP \< 90 mmHg (measured twice with a time interval of 10 min) and lactate \> 2 mmol/L Analysis per component Proportion of participants with a newly occurring component of the composite primary endpoint between Day 0 and Day 14. Sensitivity analyses Proportion of participants presenting no clinical aggravation between baseline and Day 14, with varying thresholds on the definitions of organ failures or adding different organ failures definition (e.g. neurologic, hepatic, hematologic, etc.).
Time frame: Day 28
New onset of acute kidney failure
Proportion of participants a new onset of acute kidney failure . Definition by KDIGO 3 measure. 3.0 times baseline, OR increase in serum creatinine to ≥4.0 mg/dl (≥353.6 mmol/l). The composite endpoint assesses the new onset of an event from D0
Time frame: Between Day 0 and Day 10
New onset of acute respiratory failure
Proportion of participants a new onset of acute respiratory failure. Definition by SpO2/FiO2 ≤ 315 measure The composite endpoint assesses the new onset of an event from D0
Time frame: Between Day 0 and Day 10
New onset of shock
Proportion of participants a New onset of shock. Mean Blood Pressure (MBP) \< 65 mmHg or Systolic Blood Pressure (SBP) \< 90 mmHg (measured twice with a time interval of 10 min) and lactate \> 2 mmol/L measured at the same time The composite endpoint assesses the new onset of an event from D0
Time frame: Between Day 0 and Day 10
Safety of each IMP and SCD
Proportion (events and participants with at least one event) of: * Adverse Event\* grade 3 and higher * Serious Adverse Event * Adverse Event of Special Interest
Time frame: Between Day 0 and Day 10
Safety of each IMP and SCD
Proportion (events and participants with at least one event) of: Adverse Event\* grade 3 and higher * Serious Adverse Event * Adverse Event of Special Interest
Time frame: Day 0, Day 28
Organ failure from composite primary endpoint
Proportion of participants with a newly occurring component of the composite primary endpoint
Time frame: Between Day 0 and Day 10
New onset of Acute Kidney Injury
Proportion of participants meeting KDIGO ≥ 2 or initiation of renal replacement therapy parameters
Time frame: Between Day 0 and discharge
New onset of CVPU or seizure
Proportion of participants with CVPU or seizure
Time frame: Between Day 0 and Discharge
New onset of Bleeding
Proportion of participants meeting WHO bleeding scale grade 2 or above
Time frame: Between Day 0 and Discharge
New onset of Severe anaemia
Proportion of participants with Hb level \< 8 g/dL
Time frame: Between Day 0 and Discharge
New onset of liver failure
Proportion of participants with AST or ALT ≥ 3 ULN
Time frame: Between Day 0 and Discharge
New onset of clinical severity score
Proportion of participants with a NEWS2 score ≥7
Time frame: Between Day 0 and Discharge
Intensive care strategies - oxygen therapy
Proportion of participants having received oxygen therapy
Time frame: Between Day 0 and Discharge
Intensive care strategies - RRT
Proportion of participants having received RRT
Time frame: Between Day 0 and Discharge
Intensive care strategies - blood transfusion
Proportion of participants having received blood transfusion
Time frame: Between Day 0 and Discharge
Intensive care strategies- inotropes or vasopressors
Proportion of participants having received inotropes or vasopressors
Time frame: Between Day 0 and Discharge
the viral clearance - Change in LF RT-PCR Ct
value (for each target gene) from D0
Time frame: Day 3, Day 5, Day 7, Day 9
the viral clearance - Change in LASV viral
titer from D0
Time frame: D01-D10
viral clearance - LASV RT-PCR
\<LLQ
Time frame: D01- D10
Pharmacokinetics (phase II only)
• Peak concentration (Cmax)
Time frame: Between Day 0 and Day 10
Pharmacokinetics (phase II only)
• Time to peak concentration (Tmax)
Time frame: Between Day 0 and Day 10
Pharmacokinetics (phase II only)
• Area under the curve
Time frame: Between Day 0 and Day 10
Pharmacokinetics (phase II only)
• Half-life
Time frame: Between Day 0 and Day 10
Pharmacokinetics (phase II only)
• Clearance
Time frame: Between Day 0 and Day 10
Pharmacokinetics (phase II only)
• Volume(s) of distribution
Time frame: Between Day 0 and Day 10
PK/PD (phase II only)
• Prediction of initial viral load and slope of decline
Time frame: Between Day 0 and Day 10
PK/PD (phase II only)
• Optimal dosing regimen with PK/PD modelling
Time frame: Between Day 0 and Day 10
LASV RT-PCR
LASV RT-PCR (Ct value)
Time frame: D28 if participants have a positive RT PCR at discharge
Peak CRP (Phase II stage only)
Peak CRP level (mg/L)
Time frame: D01-D10
Time to first LASV RT-PCR <LLOQ
Time to first LASV RT-PCR \<LLOQ (days)
Time frame: D01-D10
Viral resistance parameters
Frequency of LASV resistance mutations
Time frame: Between Day 0 and Day 10
Plan to share: Undecided
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Studies of the drugs tested here: Favipiravir · Ribavirin · Dexamethasone · ARN-75039