ARN-75039 Lassa Fever Treatment 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.

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