Phase 3 EPIC (EPIlepsy Cell Therapy) Clinical Trial Design: NRTX-1001 GABAergic Interneuron Cell Therapy for the Treatment of Drug-resistant Mesial Temporal Lobe Epilepsy (MTLE)
Manher Joshi1, Gautam Banik1, Marina Bershteyn1, Alessandro Bulfone1, Brianna Feld1, Luis Fuentealba1, John Hixson1, Stephanie Hughes1, Ji-Hye Jung1, Tia Kowal1, Sonja Kriks1, Rose Larios1, Ngoc Minh Le1, Seonok Lee1, Sheri Madrid1, Yves Maury1, Catherine Priest1, Cory Nicholas1
1Neurona Therapeutics
Objective:
To present the Phase 3 EPIC (EPIlepsy Cell Therapy) trial design evaluating NRTX-1001 cell therapy for the treatment of seizures due to drug-resistant mesial temporal lobe epilepsy (MTLE).
Background:
GABAergic cortical interneurons from the medial ganglionic eminence (MGE) are critical for regulating the excitability of cortical circuits. We developed a cortical MGE-type GABAergic interneuron cell therapy candidate, NRTX-1001, derived from human pluripotent stem cells for single-dose administration into seizure foci. Two Phase 1/2 multicenter, open-label trials evaluating NRTX-1001 are enrolling 38 adults with unilateral (NCT05135091) and bilateral (NCT06422923) MTLE with or without mesial temporal sclerosis (MTS). Results from 18 adults with unilateral MTLE with MTS showed NRTX-1001 was well-tolerated, with no treatment-related serious adverse events (SAEs). NRTX-1001 has demonstrated potential for clinically significant and durable seizure reduction, without neurocognitive decline, supporting advancement to Phase 3.
Design/Methods:
The Phase 3 EPIC trial is a multicenter, double-blind, randomized, sham-controlled study enrolling adults with drug-resistant MTLE. Following a 10-week baseline period, subjects randomize 2:1 to undergo NRTX-1001 administration into the affected hippocampus or a sham procedure with active or placebo immunosuppression, respectively. Subjects will be individually unblinded at their 6-month primary endpoint. Sham procedure subjects will be offered NRTX-1001 and initiate immunosuppression; NRTX-1001 subjects taper off immunosuppression at one year.
Results:
The primary efficacy endpoint is the difference between study arms in median percent change in seizure frequency (mean per 28-day average) from baseline to 4-6 months post-treatment. Secondary and exploratory endpoints include responder rates, safety, EEG, neurocognitive measures, mood, and quality of life.
Conclusions:
The Phase 3 EPIC study will assess the safety and efficacy of NRTX-1001 for drug-resistant MTLE. The study is anticipated to begin treating subjects in early 2026. A single administration of NRTX-1001 cell therapy may offer seizure control for patients who are not eligible for, or interested in, tissue resection or ablation.
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