Beeline: A Phase 3 Study in GRIN-related Neurodevelopmental Disorder
- Conditions
- GRIN-related Neurodevelopmental Disorder
- Interventions
- Drug: Placebo
- Registration Number
- NCT07224581
- Lead Sponsor
- GRIN Therapeutics, Inc.
- Brief 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Period: Participants will continue to receive radiprodil until such time as either the participant withdraws/is withdrawn from the study, sponsor terminates the study, or market access is available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
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 100
Part A, Participant:
- Diagnosed with GRIN-NDD with GRIN1, GRIN2A, GRIN2B, or GRIN2D gene variants known to result in GoF of the NMDA receptor
- Phase 3 Cohort 1 (Qualifying Seizures Cohort) ONLY: Experiencing at least 1 CMS per week and ≥4 CMS (generalized or focal) during screening
- With history of inadequate response to at least 2 standard antiseizure medications (ASMs)
- Phase 3 Cohort 2 (Without Qualifying Seizures Auxiliary Cohort) ONLY: With significant neurodevelopmental symptoms and a GRIN-CGI-S score ≥4
- On a stable dose of standard ASMs for at least 4 weeks prior to screening and should remain on stable doses throughout study participation
- On stable nonpharmacological treatments such as ketogenic diet and should remain stable throughout study participation
Part B:
- Participant has completed Part A and is eligible to continue study participation according to the judgement of the investigator and sponsor.
PART A, Participant:
- Has clinically relevant medical, neurologic, or psychiatric condition and/or behavioral disorder (including those related to GRIN-NDD) that would preclude or jeopardize participant's safe participation or study drug administration or the conduct of the study according to the judgement of the investigator or sponsor.
- Is receiving >4 standard ASMs at screening
- Has a body weight of less than 5 kg at screening
Part B:
- Participant has clinically relevant medical, neurologic, or psychiatric condition and/or behavioral disorder (including those related to GRIN-NDD) that would preclude or jeopardize participant's safe participation of study drug administration or the conduct of the study according to the judgement of the investigator or sponsor.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Radiprodil Radiprodil Liquid suspension of radiprodil, at varying concentrations depending on participant's weight. The following dose-escalation regimen (twice daily \[BID\]) will be used: Titration Period Visit 1 (Visit T1): Dose 1, Visit T2: Dose 2, Visit T3: Dose 3, Visit T4: Maintenance Dose. Placebo Placebo Liquid suspension of placebo matching radiprodil oral suspension and dose-escalation regimen.
- Primary Outcome Measures
Name Time Method Part A - Phase 3 Cohort 1 (Qualifying Seizures Cohort): Countable motor seizures (CMS) 12 weeks Part A - Phase 3 Cohort 2 (Without Qualifying Seizures Auxiliary Cohort): Adverse events (AEs), serious adverse events (SAEs), and adverse drug reactions (ADRs) 24 weeks Part B - Open-Label Extension: Adverse events (AEs), serious adverse events (SAEs), and adverse drug reactions (ADRs) Average of 2 years
- Secondary Outcome Measures
Name Time Method Part A - Phase 3 Cohort 1 (Qualifying Seizures Cohort): Proportion of participants with ≥50% reduction in CMS 12 weeks Part A - Phase 3 Cohort 1 (Qualifying Seizures Cohort): CMS-free days 12 weeks Part A - Phase 3 Cohort 1 (Qualifying Seizures Cohort): GRIN-NDD-specific Clinical Global Impression - Change [CGI-C] scale 12 weeks Part A - Phase 3 Cohort 1 (Qualifying Seizures Cohort): Aberrant Behavior Checklist-Community (ABC-2C) irritability subscale 12 weeks Part A - Phase 3 Cohort 1 (Qualifying Seizures Cohort): Vineland Adaptive Behavior Scale 3rd edition (VABS-3) daily living personal subdomain 12 weeks Part A - Phase 3 Cohort 2 (Without Qualifying Seizures Auxiliary Cohort): GRIN-CGI-C scale 24 weeks Part A - Phase 3 Cohort 2 (Without Qualifying Seizures Auxiliary Cohort): ABC-2C irritability subscale 24 weeks Part A - Phase 3 Cohort 2 (Without Qualifying Seizures Auxiliary Cohort): VABS-3 daily living personal subdomain 24 weeks PART B - Open-Label Extension: CMS frequency average of 2 years PART B - Open-Label Extension: CMS-free days average of 2 years PART B - Open-Label Extension: ABC-2C irritability subscale average of 2 years PART B - Open-Label Extension: VABS-3 daily living personal subdomain score average of 2 years PART B - Open-Label Extension: GRIN-CGI-C scale average of 2 years
Trial Locations
- Locations (20)
UCLA Health-Ronald Reagan Medical Center
🇺🇸Los Angeles, California, United States
Lucile Packard Children's Hospital
🇺🇸Palo Alto, California, United States
Children's Hospital Colorado - Anschutz Medical Campus
🇺🇸Aurora, Colorado, United States
Children's National Hospital
🇺🇸Washington D.C., District of Columbia, United States
Nicklaus Children's Hospital
🇺🇸Miami, Florida, United States
Pediatric Neurology and Epilepsy
🇺🇸Winter Park, Florida, United States
Ann & Robert H Lurie Children's Hospital of Chicago
🇺🇸Chicago, Illinois, United States
University of Iowa Hospitals & Clinics
🇺🇸Iowa City, Iowa, United States
Mid-Atlantic Epilepsy and Sleep Center
🇺🇸Bethesda, Maryland, United States
Boston Children's Hospital
🇺🇸Boston, Massachusetts, United States
Scroll for more (10 remaining)UCLA Health-Ronald Reagan Medical Center🇺🇸Los Angeles, California, United States