Island Pharmaceuticals has announced the completion of dosing in the first stage of its Phase II PROTECT trial (NCT06528457), investigating ISLA-101 as both a preventative and therapeutic measure against dengue fever. This trial marks a significant step as it is the first to explore a potential countermeasure against dengue virus in both prophylactic and therapeutic contexts.
The PROTECT trial is divided into two parts: Phase IIa, which assesses the preventative benefits of ISLA-101, and Phase IIb, which investigates its therapeutic effects. The trial aims to address the growing global concern over dengue fever, especially in regions with increasing infection rates.
Trial Design and Methodology
In the Phase IIa portion of the study, three out of four participants are receiving ISLA-101 daily for 21 days, while the fourth receives a placebo. On the fourth day, all participants are administered an attenuated strain of the dengue virus. Following infection, investigators will monitor the subjects' symptoms for 90 days, assessing their viremia curve to determine the rate of virus clearance.
The Phase IIb portion is a randomized, therapeutic study planning to enroll ten participants. These participants will be administered an attenuated strain of dengue fever on day one, with treatment commencing on day eight and continuing for two weeks. This phase will also include a placebo comparator arm to rigorously assess the therapeutic efficacy of ISLA-101.
ISLA-101: Mechanism of Action
ISLA-101 is a repurposed fenretinide that targets the nonstructural protein 5 (NS5) of the dengue virus. The drug is administered orally in gel capsule form twice daily. By targeting NS5, ISLA-101 aims to disrupt the viral replication process, potentially reducing the severity and duration of dengue fever.
Management Perspective
Island CEO Dr. David Foster stated, “Dosing the Phase IIa participants in this powerful Phase II PROTECT clinical trial is a pivotal moment for Island. We are weeks away from understanding the potential impact of our drug ISLA-101 on dengue fever.” He further added, “As the first company in the world to investigate an agent as both a prophylactic and therapeutic against dengue in a clinical setting with a challenge virus, we are proud to be conducting this innovative trial to find a preventative and/or treatment for this devastating virus, at a time when infection rates are rapidly growing around the globe.”
Dengue Fever: A Growing Global Threat
Dengue fever is a mosquito-borne disease prevalent in tropical and subtropical regions, particularly in Asia, Africa, and the Americas. The World Health Organization (WHO) reported 4.5 million cases and 2,300 deaths in the Americas region alone in 2023. The US Centers for Disease Control and Prevention (CDC) estimates that approximately 75% of dengue infections are asymptomatic, with clinical cases ranging from mild to severe. Recent outbreaks, such as those in Bangladesh, have been linked to increased mosquito populations due to high heat, humidity, and rainfall.
Current Treatment Landscape
Currently, there are two commercially available dengue vaccines: Takeda’s Qdenga (TAK-003), approved in the EU, Indonesia, Thailand, Argentina, and Brazil, and Sanofi’s Dengvaxia, approved in the US, EU, and some Asian and Latin American countries. However, there remains a significant need for effective therapeutic options, especially given the increasing prevalence and severity of dengue outbreaks.
Anticipated Timeline
Topline data from Phase IIa of the PROTECT trial is expected by the end of 2024, with Phase IIb scheduled to commence in January 2025. These results will provide critical insights into the potential of ISLA-101 as a dual-action agent against dengue fever.
