Beeline: A Phase 3 Study in GRIN-related Neurodevelopmental Disorder

Summary

The Phase 3 portion of Study RAD-GRIN-101 is a multinational, multicenter, randomized, double-blind, placebo-controlled trial followed by an open-label extension to evaluate the efficacy and safety of radiprodil in participants with GRIN-related neurodevelopmental disorder (GRIN-NDD) with a gain-of-function (GoF) genetic variant. This study will enroll two cohorts: one cohort of participants with a minimal number of countable motor seizures (with or without behavioral symptoms) (Phase 3 Cohort 1: Qualifying Seizures Cohort); and a second cohort with disease symptoms but no seizures or fewer seizures than required for the Qualifying Seizures Cohort (Phase 3 Cohort 2: Without Qualifying Seizures Auxiliary Cohort). Participants in each cohort will be randomized 1:1 to receive active drug (radiprodil) or matching placebo (Part A). Following completion of Part A, all eligible participants (including those previously on placebo) may continue into the open-label extension period (Part B) to receive radiprodil. The placebo-controlled portion is expected to be approximately 16 weeks for participants in Phase 3 Cohort 1 and 28 weeks for participants in Phase 3 Cohort 2. The study will evaluate the effect of radiprodil on seizures and non-seizure symptoms and assess safety.

Detailed Description

Participants are assigned in a 1:1 ratio to receive either radiprodil or placebo during Part A with the opportunity to receive radiprodil in the Open-Label Extension, Part B. The dosing regimen includes a fixed titration schedule over 4 weeks. This study is divided into the following parts: Part A: Randomized, double-blind, placebo-controlled * Screening/Observation Period: To assess eligibility * Titration Period (approximately 4 weeks): Titration of radiprodil or placebo to target dose * Maintenance Period (Part A): Target dose of radiprodil or placebo maintained for 12 weeks (Phase 3 Cohort 1) or 24 weeks (Phase 3 Cohort 2) * Tapering and Follow-up Period: Gradual decrease and Follow-up Period for participants not entering Part B Part B: Open-label safety follow-up period * Open-Label Treatment Period: Participants will continue to receive radiprodil until such time as either the participant withdraws/is withdrawn from the study, sponsor terminates the study, or market access is available * Tapering and Follow-up Period: Gradual decrease and follow-up observation period for participants upon leaving the study

Eligibility Criteria

Interventions