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

A Multinational, Multicenter Study With an Open-Label Phase 1b and a Randomized, Double-Blind, Placebo-Controlled Phase 3 Followed by an Open-Label Extension to Assess the Efficacy, Safety, Tolerability, and Pharmacokinetics of Radiprodil in Participants With GRIN-Related Neurodevelopmental Disorder

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.

Study Overview

• Status: Recruiting
• Conditions: GRIN-related Neurodevelopmental Disorder
• Intervention / Treatment: Drug: Radiprodil; Drug: Placebo

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

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Clinical Operations; Phone Number: +1-877-225-0014; Email: ClinicalTrials@GrinTherapeutics.com

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • Recruiting
      • UCLA Clinical & Translational Research Center
    • Palo Alto, California, United States, 94304
      • Recruiting
      • Lucile Packard Children's Hospital
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • Children's Hospital Colorado - Anschutz Medical Campus
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20010
      • Recruiting
      • Children's National Hospital
  • Florida
    • Miami, Florida, United States, 33155
      • Recruiting
      • Nicklaus Children's Hospital
    • Winter Park, Florida, United States, 32789
      • Recruiting
      • Pediatric Neurology and Epilepsy
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Recruiting
      • Iowa Health Care - Pediatric Neurology & Specialty Clinic
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Boston Children's Hospital
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Recruiting
      • Northeast Regional Epilepsy Group (NEREG) - Hackensack
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University - Harkness
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Recruiting
      • Duke Health-Duke Children's Hospital & Health Center
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Not yet recruiting
      • Cincinnati Children's Hospital Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • Children's Hospital of Philadelphia
  • Texas
    • Austin, Texas, United States, 78757
      • Recruiting
      • Child Neurology Consultants of Austin - South Austin
    • Dallas, Texas, United States, 75390
      • Not yet recruiting
      • The University of Texas Southwestern Medical Center (UTSW)
    • Houston, Texas, United States, 77030
      • Recruiting
      • UTHealth Houston
  • Washington
    • Seattle, Washington, United States, 98105
      • Recruiting
      • Seattle Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

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.

Exclusion Criteria:

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Radiprodil; Radiprodil oral suspension
Placebo Comparator: Placebo; Liquid suspension of placebo matching radiprodil oral suspension and dose-escalation regimen.	Drug: Placebo; Placebo-to-match radiprodil oral suspension

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: GRIN Therapeutics, Inc.
• Collaborators: Aziende Chimiche Riunite Angelini Francesco S.p.A
• Investigators: Study Director: Russell Chin, GRIN Therapeutics, Inc.; Study Director: Alex Cepeda, GRIN Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): January 5, 2026
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): July 1, 2028

Study Registration Dates

• First Submitted: October 31, 2025
• First Submitted That Met QC Criteria: October 31, 2025
• First Posted (Actual): November 4, 2025

Study Record Updates

• Last Update Posted (Actual): February 27, 2026
• Last Update Submitted That Met QC Criteria: February 25, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: GRIN2B; GRIN2A; GRIN1; GRIN2D; Beeline; GRIN-NDD
• Additional Relevant MeSH Terms: radiprodil
• Other Study ID Numbers: Beeline RAD-GRIN-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No