GRIN Therapeutics has commenced the Astroscape study, a clinical trial evaluating the efficacy and safety of radiprodil in pediatric patients with Tuberous Sclerosis Complex (TSC) and Focal Cortical Dysplasia (FCD) type II. This open-label trial aims to address the urgent need for effective treatments for seizures associated with these neurodevelopmental disorders, particularly in cases where conventional anti-seizure medications have failed.
Radiprodil: A Novel Approach to Seizure Control
Radiprodil is a selective and potent negative allosteric modulator of the N-methyl-D-aspartate (NMDA) receptor subtype 2B (GluN2B). This mechanism of action is particularly relevant to TSC and FCD type II, as lesions associated with these conditions often overexpress GluN2B. By modulating the activity of this receptor, radiprodil aims to reduce neuronal excitability and, consequently, seizure frequency and severity. Preclinical studies have demonstrated radiprodil's antiseizure effect in models characterized by enhanced GluN2B-NMDA transmission, and a previous phase 1 study in GRIN-related neurodevelopmental disorder showed significant impacts on seizure frequency.
Astroscape Study Design and Objectives
The Astroscape study is enrolling children and adolescents between 6 months and 18 years of age with TSC or FCD type II who continue to experience seizures despite treatment with at least two anti-seizure medications. The target enrollment is approximately 20 participants with TSC and 10 participants with FCD type II. The study's primary objectives include evaluating the safety and tolerability of radiprodil, assessing its pharmacokinetic profile, and determining its effect on the frequency and severity of epileptic seizures. Secondary endpoints will assess non-seizure outcomes, such as symptoms related to behavior, sleep, and quality of life. Participants who complete the treatment phase may have the option to enroll in a long-term extension study.
Addressing Unmet Needs in TSC and FCD Type II
There are currently no approved disease-modifying therapies for FCD type II and no targeted therapies for TSC. Current treatments primarily focus on managing symptoms, particularly seizures, with anti-seizure medications. However, many patients do not achieve full seizure control with medication alone, and some require surgery.
TSC is a multi-system genetic disorder caused by mutations in the TSC1 or TSC2 genes, leading to the formation of non-cancerous tumors in various organs, including the brain. It is the leading genetic cause of epilepsy and autism. FCD type II is a rare disorder characterized by malformations of cortical development, resulting in a high risk of seizures and disruption of brain function. While anti-seizure medications are the standard of care, only about one in five individuals with FCD type II achieve sufficient seizure control with these medications alone.
Challenges and Considerations
Bruce Leuchter, MD, president and chief executive officer at Neurvati Neurosciences and GRIN Therapeutics, emphasized the heterogeneity of TSC and FCD type II, noting that symptoms and progression can vary widely. He highlighted the importance of careful planning in clinical trial inclusion and exclusion criteria to reflect the patient experience while ensuring a consistent group for analysis. The study team will consider each participant's specific symptoms and severity levels to ensure meaningful results for these patient communities.
The estimated primary completion date for the Astroscape study is July 2025, with an estimated study completion date of July 2026. No interim analyses are planned.
