ARN-75039 Lassa Fever Treatment in West Africa

A Phase 2 Study to Evaluate Safety, Tolerability, And Virologic Efficacy of ARN-75039 For the Treatment of Lassa Fever in West Africa

This multicenter, randomized, open-label Phase 2 clinical trial evaluates the safety, tolerability, and virologic efficacy of ARN-75039, a novel oral antiviral, for treating Lassa fever in hospitalized adults in West Africa. The study is conducted within the INTEGRATE platform and compares two oral dose regimens of ARN-75039 (100 mg BID and 50 mg BID) with intravenous ribavirin, the locally mandated standard of care.

Approximately 135 participants with RT-PCR-confirmed Lassa virus infection will be enrolled and randomized 1:1:1 to receive ARN-75039 high dose, ARN-75039 low dose, or ribavirin for 10 days, followed by safety and efficacy follow-up through Day 28. The primary objectives are to assess safety and tolerability and to evaluate antiviral activity, as measured by the change in slope of Lassa virus RT-PCR cycle threshold (Ct) values from Day 1 to Day 10, in participants with low baseline viral load Ct values. Secondary objectives include additional virologic, pharmacokinetic, and clinical outcome assessments, including time to viral clearance, symptom resolution, organ failure, and mortality.

ARN-75039 is a small-molecule viral entry inhibitor targeting the Lassa virus glycoprotein complex and has demonstrated potent antiviral activity and favorable safety and pharmacokinetic profiles in preclinical models and Phase 1 clinical studies. This study aims to inform dose selection and support further clinical development of ARN-75039 as a potential treatment for Lassa fever.

Study Overview

• Status: Active, not recruiting
• Conditions: Lassa Fever
• Intervention / Treatment: Drug: ARN-75039 high; Drug: ARN-75039 low; Drug: Intravenous ribavirin

Detailed Description

This Phase 2, randomized, open-label, controlled clinical trial, conducted under the INTEGRATE platform, evaluates the safety, tolerability, antiviral activity, and pharmacokinetics of ARN-75039 in adults hospitalized with RT-PCR-confirmed Lassa fever. The trial is conducted at specialized treatment centers in West Africa that have established capacity for Lassa fever diagnosis, inpatient management, and pharmacovigilance. It operates under coordinated African and U.S. regulatory oversight.

Participants are randomized 1:1:1 to receive one of three interventions for a 10-day inpatient treatment period: a high-dose oral regimen of ARN-75039, a low-dose oral regimen of ARN-75039, or intravenous ribavirin administered according to the locally mandated "Irrua regimen." Randomization is stratified by Lassa virus lineage and baseline viral load, as measured by RT-PCR cycle threshold (Ct) values. All participants receive optimized supportive care consistent with INTEGRATE platform standards and local site capabilities.

ARN-75039 is a novel, orally administered small-molecule antiviral that inhibits viral entry by targeting the Lassa virus glycoprotein complex and blocking membrane fusion. The dose regimens evaluated in this study were selected based on preclinical efficacy data, translational pharmacology, and Phase 1 clinical studies demonstrating favorable safety, tolerability, and pharmacokinetic profiles. The study incorporates an initial loading phase followed by tapered twice-daily dosing to rapidly achieve and maintain plasma concentrations associated with antiviral activity while preserving tolerability.

The primary efficacy analysis focuses on the change in slope of Lassa virus RT-PCR Ct values between Day 1 and Day 10 in participants with low baseline Ct values, reflecting viral load dynamics during acute infection. Additional virologic assessments include time to first RT-PCR result below the lower limit of quantification, time to undetectable viral RNA, and longitudinal changes in Ct value across predefined time points. Lineage-specific and baseline viral load-stratified analyses are planned to characterize antiviral effects across circulating Lassa virus variants.

Safety assessments include continuous monitoring of treatment-emergent adverse events, serious adverse events, laboratory abnormalities, vital signs, and clinically significant changes in electrocardiograms and physical examinations. Adverse events are graded using standardized criteria and reviewed by an independent Data and Safety Monitoring Board operating under the INTEGRATE master protocol. Clinical outcome measures include mortality, organ failure, need for intensive care-level support, and time to symptom resolution and hospital discharge.

Pharmacokinetic sampling is performed in participants receiving ARN-75039 to characterize systemic exposure, including peak and trough concentrations, area under the concentration-time curve, half-life, and apparent clearance. These data will support pharmacokinetic/pharmacodynamic modeling to define further exposure-response relationships and inform dose optimization for future studies.

Exploratory objectives include evaluating viral genomic sequences from selected post-dose samples to assess the potential emergence of resistance-associated mutations, and detailed monitoring of Lassa fever-related symptoms and biomarkers to support the development of future composite clinical endpoints.

Participants are followed for 28 days from treatment initiation, including the inpatient dosing period and post-treatment follow-up assessments. Study conduct adheres to International Council for Harmonisation Good Clinical Practice guidelines and applicable national and international regulatory requirements. The results of this study are intended to support further clinical development and potential regulatory approval of ARN-75039 for the treatment of Lassa fever.

• Study Type: Interventional
• Enrollment (Estimated): 135
• Phase: Phase 2

Contacts and Locations

Study Locations

• Nigeria
  • Bauchi, Nigeria
    • Abubakar Tafawa Balewa University Teaching Hospital
  • Irrua, Nigeria, 310115
    • Irrua Specialist Teaching Hospital
  • Ondo State
    • Owo, Ondo State, Nigeria
      • Federal Medical Centre, Owo
• United States
  • California
    • Carlsbad, California, United States, 92008
      • Arisan Therapeutics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Participants must meet all of the following criteria to be eligible for enrollment:

• Age ≥ 18 years
• Hospitalized with clinical disease consistent with Lassa fever
• Positive plasma Lassa virus RT-PCR at screening
• Requires hospitalization for Lassa fever per local clinical guidelines
• Able to provide written informed consent, or consent provided by a legally authorized representative.

Exclusion Criteria:

Participants will be excluded if they meet any of the following criteria:

• Pregnant (confirmed by positive urine pregnancy test in women of childbearing potential)
• Receipt of specific drug therapy for Lassa fever (e.g., ribavirin, direct antivirals, or host-directed therapies including corticosteroids) within 15 days before enrollment
• Prior vaccination against Lassa fever
• History of severe gastrointestinal disease
• History of chronic generalized pruritus
• History of severe chronic liver disease
• History of severe cardiac disorder

Sex and Reproductive Criteria

• Women of childbearing potential must have a negative pregnancy test at screening
• Breastfeeding is not permitted during the treatment period and early follow-up
• Participants must agree to comply with protocol-defined contraception requirements

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ARN-75039: 100 mg maintenance (high oral dose); ARN-75039 is an investigational oral antiviral agent administered as tablets. This high dose regimen includes a 300 mg initial dose and 200 second dose on day 1, followed by a 200 mg BID dose on day 2 and 100 mg BID days 3-10.	Drug: ARN-75039 high; ARN-75039 (100 mg maintenance) high dose
Experimental: ARN-75039: 50 mg maintenance (low oral dose); ARN-75039 is an investigational oral antiviral agent administered as tablets. This high dose regimen includes a 150 mg initial dose and 100 second dose on day 1, followed by a 100 mg BID dose on day 2 and 50 mg BID days 3-10.	Drug: ARN-75039 low; ARN-75039 (50 mg maintenance) low dose
Active Comparator: Ribavirin intravenous (IV); Standard of Care "Irrua regimen"	Drug: Intravenous ribavirin; Irrua Regimen SOC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events (TEAEs) Grade ≥3	Type and frequency of treatment-emergent adverse events of Grade 3 or higher	Day 1 through Day 28
Change in Viral Load Slope (RT-PCR Ct Values)	Change in slope of Lassa virus RT-PCR cycle threshold (Ct) values between Day 1 and Day 10 in participants with low baseline Ct values.	Day 1 to Day 10

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Viral Load Slope in Participants with Other Baseline Ct Values	Change in slope for LASV RT-PCR Ct values between Day 1 and Day 10, for subjects with other baseline Ct values (to be determined [TBD], subsequent to RT-PCR methods validation).	Day 1 to Day 10
Change in RT-PCR Ct Values at Prespecified Timepoints (Change in Ct values. between Day 1 and Days 2, 3, 4, 6, 8, and 10).	Change in Ct values between Day 1 and each of Days 2, 3, 4, 6, 8, and 10 for the ARN-75039 arms vs SOC for those with baseline Ct <30 (or other Ct values TBD).	Day 1 to Day 10
Time to First RT-PCR Result Below Lower Limit of Quantification (LLOQ)	Time to reach lower limit of quantification [LLOQ] and undetectable Ct values.	Day 1 to Day 28
Time to First Undetectable Lassa Virus RT-PCR Result	Time to reach undetectable Ct values.	Day 1 to Day 28
Proportion of Participants With RT-PCR <LLOQ	LASV RT-PCR <LLOQ (% of participants) for specified baseline Ct values (TBD).	Day 1 to Day 28
Proportion of Participants With Undetectable RT-PCR	LASV RT-PCR undetectable (% of participants) for specified baseline Ct values TBD.	Day 1 to Day 28
Estimated Baseline Lassa Virus RT-PCR Cycle Threshold (Ct) Value (Intercept) from Linear Mixed-Effects Model	Estimated baseline Lassa virus RT-PCR cycle threshold (Ct) value derived from a linear mixed-effects model of longitudinal Ct measurements collected between Day 1 and Day 10. Results will be reported as model-estimated mean Ct value (Ct units).	Day 1
Estimated Rate of Change in Lassa Virus RT-PCR Ct Value (Ct Units per Day) from Linear Mixed-Effects Model.	Estimated rate of change (slope) in Lassa virus RT-PCR cycle threshold (Ct) values over time, calculated using a linear mixed-effects model of longitudinal Ct measurements from Day 1 through Day 10. Results will be reported as mean change in Ct units per day (Ct/day).	Day 1 to Day 10
Change in Ct values stratified by Lassa lineage (Ct <30)	Change in Ct values stratified by Lassa lineage for subjects with baseline Ct <30 or other baseline Ct values TBD.	Day 1 to Day 10
Pharmacokinetic Outcome: ARN-75039 AUC₀-t	Area under the plasma concentration-time curve from time 0 to time of last quantifiable concentration.	Day 1 through Day 10
Pharmacokinetic Outcome: ARN-75039 AUC₀-∞	Area under plasma concentration-time curve from time 0 to infinity.	Day 1 through Day 10
Pharmacokinetic Outcome: ARN-75039 Cmax	Maximum observed plasma concentration.	Day 1 through Day 10
Pharmacokinetic Outcome: ARN-75039 Ctrough (Cmin0-24hr)	Trough concentration (Ctrough) exposures: Cmin(0-24hr) exposures taken prior to first dose on Days 2, 4, and 10.	Day 1 through Day 10
Pharmacokinetic Outcome: ARN-75039 Tmax	Time to reach Cmax	Day 1 through Day 10
Pharmacokinetic Outcome: t½	ARN-75039 half-life	Day 1 through Day 10
Pharmacokinetic Outcome: ARN-75039 apparent clearance (CL/F)	Apparent Clearance	Day 1 through Day 10
Pharmacokinetic Outcome: ARN-75039 apparent volume of distribution (Vz/F)	Apparent volume of distribution during the terminal phase.	Day 1 through Day 10
Association Between ARN-75039 Plasma Exposure (AUC₀-t) and Change in Lassa Virus RT-PCR Ct Value.	The association between individual plasma exposure to ARN-75039, measured as area under the concentration-time curve from time 0 to time of last quantifiable concentration (AUC₀-t), and change in Lassa virus RT-PCR cycle threshold (Ct) values from Day 1 to Day 10 will be evaluated using linear regression modeling. Results will be reported as regression slope (change in Ct per unit increase in AUC) with corresponding 95% confidence intervals.	Day 1 to Day 10
Time to Resolution of ≥ Grade 2 TEAEs	Time to resolution of ≥ Grade 2 treatment-emergent adverse event (TEAE)	Day 1 to Day 28
Incidence of AEs with Grade ≥3	Clinical Outcome: Adverse event (AE) grade ≥3 (% of participants)	Day 1 to Day 28
Incidence of Serious Adverse Events (SAEs)	Clinical Outcome: Serious adverse event (SAE) (% of participants)	Day 1 to Day 28
Trial Drug Interruption or Withdrawal	Clinical outcome: Trial drug interruption or withdrawal	Day 1 to Day 28
All-Cause Mortality	Clinical Outcome: Mortality (% of participants)	Day 1 to Day 28
Time to Death	Clinical Outcome	Day 1 to Day 28
Time to First Organ Failure	Clinical Outcome	Day 1 to Day 28
Use of Rescue Medication	Clinical Outcome	Day 1 to Day 28
New Onset Kidney Disease Improving Global Outcomes (KDIGO) Score ≥2	Clinical Outcome: New onset of Kidney Disease Improving Global Outcomes (KDIGO) score ≥2 (% of participants)	Day 1 to Day 28
New Onset Altered Consciousness or Seizure (ACVPU Scale)	Clinical Outcome: New onset (ACVPU) scale (measured level of consciousness according to scale of: A = Alert, C = Confusion, V = Voice, P = Pain, U = Unresponsive) or seizure (% of participants)	Day 1 to Day 28
New Onset WHO Bleeding Scale Grade ≥2	Clinical Outcome: New onset of World Health Organization (WHO) bleeding scale Grade ≥2 (% of participants)	Day 1 to Day 28
New Onset hemoglobin <8 g/dL	Clinical Outcome: New onset of hemoglobin <8 g/dL (% of participants)	Day 1 to Day 28
New Onset AST or ALT ≥3× normal ULN for each	Clinical Outcome: New onset aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥3 upper limit of normal (ULN) AST or ALT ≥3 ULN (% of participants)	Day 1 to Day 28
Receipt of Advanced Supportive Care	Clinical Outcome: Advanced supportive care received (% of participants)	Day 1 to Day 28
Peak C-Reactive Protein (CRP) Level	Clinical Outcome: Peak C-reactive protein (CRP) level (mg/L)	Day 1 to Day 28
Exploratory Virologic Outcome: Emergence of Resistance-Associated Viral Mutations - Detection of new-onset resistance mutations via viral RNA sequencing.	Viral ribonucleic acid (RNA) gene sequencing will be performed on selected post-dose samples for comparison with baseline samples to evaluate potential emergence of resistance mutations to the investigational agent. Phenotypic testing may be pursued if concerning variants are identified.	Day 1 to Day 28

Collaborators and Investigators

• Sponsor: Arisan Therapeutics, Inc.
• Collaborators: ANRS, Emerging Infectious Diseases; Bernhard Nocht Institute for Tropical Medicine; Battelle Memorial Institute; Federal Medical Centre, Owo; Alliance for International Medical Action; Irrua Specialist Teaching Hospital; JPEO, Chemical, Biological, Radiological, and Nuclear, Medical
• Investigators: Study Chair: Ken McCormack, PhD, Arisan Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): February 14, 2026
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: February 2, 2026
• First Submitted That Met QC Criteria: February 11, 2026
• First Posted (Actual): February 19, 2026

Study Record Updates

• Last Update Posted (Actual): June 1, 2026
• Last Update Submitted That Met QC Criteria: May 28, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Neglected tropical diseases; Lassa virus; Emerging infectious diseases; Viral hemorrhagic fever; Viral entry inhibitor; Ribavirin comparator; INTEGRATE platform trial; Lassa virus infection; RT-PCR viral load; ARN-75039; Glycoprotein fusion inhibitor
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; RNA Virus Infections; Virus Diseases; Communicable Diseases; Arenaviridae Infections; Pathological Conditions, Signs and Symptoms; Communicable Diseases, Emerging; Hemorrhagic Fevers, Viral; Lassa Fever; Neglected Diseases
• Other Study ID Numbers: ARN-75039-201; MCDC2001-010 (Other Grant/Funding Number: U.S. Department of Defense)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: May currently be shared in cases of compassionate use.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No