Australian antiviral drug development company, Island Pharmaceuticals (ASX:ILA) has provided top-line results from its Phase 2a/b PROTECT Trial of ISLA101 in a human challenge model of dengue virus infection.
The company stated that an initial review indicates that ISLA-101 was associated with both a reduction in viral load and a clinically meaningful decrease in symptoms in the preventive cohort. ISLA-101 was also associated with tangible drug effects in the treatment cohort.
Island’s Phase 2a/b PROTECT trial included two patient cohorts. The Phase 2a arm examined ISLA-101’s ability to prevent dengue fever in four subjects, randomised three to one, active or placebo. The Phase 2b cohort included 10 subjects, randomised eight to two, active or placebo. The trial assessed whether ISLA-101 can reduce virus levels and symptoms in subjects already infected with the dengue challenge virus.
The challenge virus was provided by the US Army under a Cooperative Research and Development Agreement (CRADA), alongside support from the Walter Reed Army Institute of Research (WRAIR). This strain is weaker than the wild-type dengue, yet subjects are still infected with a replicating virus and experience mild to moderate dengue symptoms. The trial was conducted at the State University of New York Upstate, in accordance with the SUNY Dengue Human Infection Model, which is a robust protocol that elicits detectable dengue viral load and symptoms.
"While other small molecules have been explored in this model, ISLA-101 is the first to demonstrate a potential benefit," said Island.
In the Phase 2a arm, subjects received ISLA-101 or placebo three days prior to being inoculated with dengue to investigate whether ISLA-101 can reduce or prevent viral load and dengue symptoms compared to the placebo control.
Island said ISLA-101 demonstrated clinically meaningful anti-dengue activity, which included a material reduction in viral load and symptoms.
During Phase 2b, subjects were inoculated with dengue, then administered either ISLA-101 or placebo, seven days post-virus exposure. The primary endpoint of Phase 2b was to assess viral load in subjects. Island said that, based on a preliminary review, ISLA-101 impacted viral replication. Because some subjects were viral and symptomatic at the time of first dosing, the alterations in symptoms were less pronounced and are being investigated further, the company said.
Island’s CEO and Managing Director, Dr David Foster, said, “We are very excited to share top-line results from our successful Phase 2a/b PROTECT study, which show clear anti-dengue activity in humans.”
“Despite being in a small number of subjects, initial findings are highly encouraging and advocate for continued development of ISLA-101. We are pleased to advance the pre-clinical work from both Monash and Harvard to further highlight the potential for ISLA-101 as a measure to impact a widespread condition with no treatment.
“Additional work into the dataset alongside our Scientific and Clinical Advisory Boards is ongoing and will be the primary focus for the Company in the near term. We are confident that additional data will provide a clear determination for the next steps in our clinical trial pipeline and look forward to sharing this as it materialises," said Dr Foster.