ARN-75039 Lassa Fever Treatment in West Africa

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.