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

NCT07224581 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: Beeline RAD-GRIN-101
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 17

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.

Conditions

GRIN-related Neurodevelopmental Disorder

Keywords

Beeline; GRIN1; GRIN2A; GRIN2B; GRIN2D; GRIN-NDD

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (13)

• 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

Study Arms (2)

Radiprodil

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

Liquid suspension of placebo matching radiprodil oral suspension and dose-escalation regimen.

Drug: Placebo

Interventions

Radiprodil DRUG

Radiprodil oral suspension

Radiprodil

Placebo DRUG

Placebo-to-match radiprodil oral suspension

Placebo

Eligibility Criteria

• Age: 1 Month - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GRIN Therapeutics, Inc.: lead
• Aziende Chimiche Riunite Angelini Francesco S.p.A: collaborator

Study Sites (17)

UCLA Clinical & Translational Research Center

Los Angeles, California, 90095, United States

RECRUITING

Lucile Packard Children's Hospital

Palo Alto, California, 94304, United States

RECRUITING

Children's Hospital Colorado - Anschutz Medical Campus

Aurora, Colorado, 80045, United States

RECRUITING

Children's National Hospital

Washington D.C., District of Columbia, 20010, United States

RECRUITING

Nicklaus Children's Hospital

Miami, Florida, 33155, United States

RECRUITING

Pediatric Neurology and Epilepsy

Winter Park, Florida, 32789, United States

RECRUITING

Iowa Health Care - Pediatric Neurology & Specialty Clinic

Iowa City, Iowa, 52242, United States

RECRUITING

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

Northeast Regional Epilepsy Group (NEREG) - Hackensack

Hackensack, New Jersey, 07601, United States

RECRUITING

Columbia University - Harkness

New York, New York, 10032, United States

RECRUITING

Duke Health-Duke Children's Hospital & Health Center

Durham, North Carolina, 27705, United States

RECRUITING

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

NOT YET RECRUITING

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Child Neurology Consultants of Austin - South Austin

Austin, Texas, 78757, United States

RECRUITING

The University of Texas Southwestern Medical Center (UTSW)

Dallas, Texas, 75390, United States

NOT YET RECRUITING

UTHealth Houston

Houston, Texas, 77030, United States

RECRUITING

Seattle Children's Hospital

Seattle, Washington, 98105, United States

RECRUITING

MeSH Terms

Interventions

radiprodil

Study Officials

• Alex Cepeda

  GRIN Therapeutics, Inc.

  STUDY DIRECTOR

• Russell Chin

  GRIN Therapeutics, Inc.

  STUDY DIRECTOR

Central Study Contacts

Clinical Operations

CONTACT

+1-877-225-0014; ClinicalTrials@GrinTherapeutics.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: study personnel, sponsor
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 31, 2025
• First Posted: November 4, 2025
• Study Start: January 5, 2026
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): July 1, 2028
• Last Updated: February 27, 2026

Record last verified: 2026-02

Locations

US (17)