Irrua

Researchers are evaluating the safety, tolerability, and antiviral effectiveness of ARN-75039, a new oral antiviral medication, for treating Lassa fever in adults hospitalized in West Africa. This Phase 2, randomized, open-label clinical trial is conducted within the INTEGRATE platform and compares two different oral doses of ARN-75039 (100 mg twice daily and 50 mg twice daily) with the standard intravenous ribavirin treatment. The study aims to assess antiviral activity by measuring changes in viral load and includes participants confirmed to have Lassa virus infection by RT-PCR. Participants are randomly assigned in equal groups to receive either the high-dose ARN-75039, low-dose ARN-75039, or intravenous ribavirin for a 10-day inpatient treatment period. The ARN-75039 treatment includes an initial loading phase followed by tapered twice-daily oral dosing designed to achieve and maintain effective drug levels while minimizing side effects. All participants also receive supportive care according to local standards. The study is conducted at specialized centers equipped for Lassa fever management and pharmacovigilance under coordinated African and U.S. regulatory oversight. During the 28-day study period, which includes treatment and follow-up phases, participants undergo continuous safety monitoring for adverse events and clinical outcomes such as symptom resolution, organ failure, and mortality. Researchers collect viral load data through RT-PCR testing to evaluate antiviral effects and perform pharmacokinetic sampling in patients receiving ARN-75039 to understand drug exposure. Additional assessments include laboratory tests, electrocardiograms, physical exams, and monitoring for potential viral resistance. The results will help guide further development of ARN-75039 as a treatment for Lassa fever.

Lassa fever is a viral hemorrhagic fever causing thousands of deaths annually in West Africa, with about 12% in-hospital mortality. It is primarily spread through contact with rodent excreta and can occasionally spread between humans, leading to hospital outbreaks. Current treatment relies on ribavirin, which has concerns regarding toxicity, effectiveness, and cost, creating an urgent need for new, safer medications. The World Health Organization has prioritized Lassa fever for urgent research, and the INTEGRATE consortium brings together international partners to address this need through clinical trials. This multinational, multi-center phase II-III trial evaluates the safety and effectiveness of three investigational drugs—Favipiravir, Dexamethasone, and ARN-75039 (in high and low doses)—compared to the standard treatment with ribavirin in hospitalized patients confirmed to have Lassa fever. The study uses an open-label, randomized design with parallel arms, assessing each investigational drug against the standard of care. The trial includes a hospitalization period of 10 days followed by a 28-day follow-up. Participants will be monitored throughout hospitalization and follow-up for outcomes including death and new organ failure events such as kidney, respiratory failure, or shock within the initial 10 days. Safety and tolerability of treatments will be assessed along with clinical, virological, and biological parameters. Pharmacokinetics and pharmacodynamics data will be collected to optimize dosing. The total study duration for each participant is 28 days, with close clinical and laboratory monitoring during and after treatment.

Lassa fever is a severe and often deadly disease caused by the Lassa virus, primarily affecting people in West Africa. There are currently no vaccines, and treatment is limited to supportive care and the antiviral drug ribavirin. Researchers are studying whether adding dexamethasone, a corticosteroid known to reduce harmful immune responses in infections like COVID-19 and meningitis, can help prevent immune-related damage in moderate to severe cases of Lassa fever. This is a phase II clinical trial to evaluate the safety and tolerability of dexamethasone alongside standard ribavirin treatment. Participants will be randomly assigned to receive either standard antiviral therapy with ribavirin alone or ribavirin plus dexamethasone. Dexamethasone will be given for 10 days, starting with intravenous administration for the first 48 hours, then potentially switching to oral dosing if the study doctor decides. Ribavirin will be administered intravenously for 10 days following national guidelines. The study will monitor how dexamethasone affects disease progression, immune and virus activity, and drug levels in the body. During the study, participants will be followed up until 10 days after enrollment to track any side effects or serious adverse events. Researchers will assess health status using clinical signs and laboratory tests, including liver and kidney function. The main measure is the proportion of participants experiencing treatment-related side effects. This trial aims to better understand the safety of adding dexamethasone to current Lassa fever treatment and its impact on the disease.

Researchers are evaluating whether the smallpox vaccine can reduce the number of secondary monkeypox cases and decrease symptom severity in people exposed to monkeypox. This phase 4, pragmatic, adaptive, multi-site cluster randomized controlled trial focuses on households where one or more individuals have confirmed monkeypox infection. The study aims to compare outcomes between vaccinated and unvaccinated groups within these households. Participants will be assigned by household to receive either a single dose of the Bavarian Nordic smallpox vaccine or a single dose of the typhoid vaccine as a control at the start of the study. The vaccination is given once at baseline, and households are monitored to assess the effect of the vaccine on preventing monkeypox and reducing symptoms. During the 8-week study period, researchers will track confirmed monkeypox cases using RT-PCR tests and measure symptom severity. Participants will be observed for the development of monkeypox and the progression of symptoms. Safety and effectiveness outcomes will be collected to understand the vaccine's impact as post-exposure prophylaxis in household contacts of monkeypox cases.