ISTH/ANRS 0409s INTEGRATE Lassa Fever Study

NCT06212336 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: ISTH/ANRS 0409s INTEGRATE
• Study Type: interventional
• Target: 1,755
• Locations: 2 countries
• Sites: 4

Brief Summary

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.).

Conditions

Lassa Fever

Keywords

emerging infectious diseases; viral hemorrhagic fever; AFRICA; adult; adolescent

Outcome Measures

Primary Outcomes (4)

• 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.).

  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

  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

  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

  Between Day 0 and Day 10

Secondary Outcomes (27)

• Safety of each IMP and SCD

  Between Day 0 and Day 10

• Safety of each IMP and SCD

  Day 0, Day 28

• Organ failure from composite primary endpoint

  Between Day 0 and Day 10

• New onset of Acute Kidney Injury

  Between Day 0 and discharge

• New onset of CVPU or seizure

  Between Day 0 and Discharge

Other Outcomes (1)

• Viral resistance parameters

  Between Day 0 and Day 10

Study Arms (6)

Favipiravir 1600

EXPERIMENTAL

Oral favipiravir: 2400 mg BID D1; 1600 mg BID D2-D10

Drug: Favipiravir

Ribavirin

ACTIVE COMPARATOR

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

Favipiravir 1200 + ribavirin

EXPERIMENTAL

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

Ribavirin + dexamethasone

EXPERIMENTAL

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

EXPERIMENTAL

• 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

EXPERIMENTAL

• ARN-75039 low dose * D1: 150mg (morning), 100mg (evening) * D2: 100mg BID * D3-10: 50mg BID

Drug: ARN-75039 low dose

Interventions

Favipiravir DRUG

Interventional Medicinal Product (IMP)

Favipiravir 1200 + ribavirin; Favipiravir 1600; Ribavirin

Ribavirin DRUG

Control arm

Also known as: Standard of care

Favipiravir 1200 + ribavirin; Ribavirin + dexamethasone

Dexamethasone DRUG

Interventional Medicinal Product (IMP)

Ribavirin + dexamethasone

ARN-75039 high dose DRUG

Investigational Medicinal Product

ARN-75039 high dose

ARN-75039 low dose DRUG

Investigational Medicinal Product

ARN-75039 low dose

Eligibility Criteria

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

You may qualify if:

• Clinical disease with signs and symptoms suggestive for LF
• Positive plasma LASV RT-PCR
• Participant requires hospitalization per the local guidelines
• Participant or their legally authorized representative is able and willing to sign the informed consent

You may not qualify if:

• Unwilling to provide informed consent
• Positive pregnancy test
• Unwilling to provide informed consent
• History of allergic reaction or other contra-indication to ribavirin according to the Reference safety document
• Has received a vaccine against LF
• Sub-protocols
• Favipiravir high dose sub-protocol
• Treatment contraindicated with favipiravir according to the Reference safety document
• Pre-existing liver failure
• Severe symptomatic gout/hyperuricemia
• History of QT prolongation or arrhythmia or other cardiac disorders
• PR interval ≥ 200 ms
• Hypersensitivity to excipients
• Inability to take oral drug (e.g. encephalopathy, severe vomiting)
• Favipiravir-Ribavirin sub-protocol

Sponsors & Collaborators

• Irrua Specialist Teaching Hospital: lead
• Alliance for International Medical Action: collaborator
• University of Bordeaux: collaborator
• Bernhard Nocht Institute for Tropical Medicine: collaborator
• Federal Medical Centre, Owo: collaborator
• Programme PAC-CI, Site ANRS-MIE de Côte d'Ivoire: collaborator
• Fondation pour la Recherche Scientifique, Benin: collaborator
• Médecins Sans Frontières, Belgium: collaborator
• Alex Ekwueme Federal University Teaching Hospital: collaborator
• Donka Hospital, Conakry: collaborator
• Centre de Recherche Médicale de Lambaréné: collaborator
• University of Hamburg-Eppendorf: collaborator
• Phebe Hospital, Liberia: collaborator
• University of North Carolina: collaborator
• ANRS, Emerging Infectious Diseases: collaborator

Study Sites (4)

Phebe Hospital

Suacoco, Bong County, Liberia

NOT YET RECRUITING

Irrua Specialist Teaching Hospital

Irrua, Edo, Nigeria

RECRUITING

Federal Medical Center Owo

Owo, Ondo State, Nigeria

RECRUITING

Abubakar Tafawa Balewa University Teaching Hospital

Bauchi, Nigeria

NOT YET RECRUITING

MeSH Terms

Conditions

Lassa Fever; Communicable Diseases, Emerging; Hemorrhagic Fevers, Viral

Interventions

favipiravir; Ribavirin; Standard of Care; Dexamethasone

Condition Hierarchy (Ancestors)

Arenaviridae Infections; RNA Virus Infections; Virus Diseases; Infections; Communicable Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Marie MD JASPARD, MD

  ALIMA - The Alliance for International Medical Action - Paris, France

  STUDY DIRECTOR

• Sylvanus OKOGBENIN, MD

  Irrua Specialist Teaching Hospital Irrua - Edo State, Nigeria

  PRINCIPAL INVESTIGATOR

• Michael RAMHARTER, MD

  Bernhard Nocht Institute for Tropical Medicine Bernhard-Nocht-Hamburg, Germany

  STUDY CHAIR

Central Study Contacts

Camille FRITZELL, PHD

CONTACT

+33 6 58 80 90 12; camille.fritzell@coral.alima.ngo

Sylvain JUCHET

CONTACT

+33 6 58 80 90 12; sylvain.juchet@coral.alima.ngo

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participant, Investigator, Outcomes Assessor
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: a) Arms Intervention/ treatement Arm 1: SCD: ribavirin Arm:2 Favirpiravir 1600 Arm 3: Favipiravir 1200+ribavirin Arm 4: Ribavirin + dexamethasone Arm 5: ARN-75039 high dose (100) Arm 6: ARN-75039 low dose (50)

Study Record Dates

• First Submitted: September 22, 2023
• First Posted: January 18, 2024
• Study Start: May 2, 2025
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: February 4, 2026

Record last verified: 2026-02

Locations

NG (3); LI (1)