Beeline: A Phase 3 Study in GRIN-related Neurodevelopmental Disorder
Purpose
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.
Condition
- GRIN-related Neurodevelopmental Disorder
Eligibility
- Eligible Ages
- Between 1 Month and 18 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
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 Design
- Phase
- Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Care Provider, Investigator)
- Masking Description
- study personnel, sponsor
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
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. |
|
|
Placebo Comparator Placebo |
Liquid suspension of placebo matching radiprodil oral suspension and dose-escalation regimen. |
|
Recruiting Locations
Los Angeles, California 90095
Palo Alto, California 94304
Aurora, Colorado 80045
Washington D.C., District of Columbia 20010
Miami, Florida 33155
Winter Park, Florida 32789
Iowa City, Iowa 52242
Boston, Massachusetts 02115
Hackensack, New Jersey 07601
New York, New York 10032
Durham, North Carolina 27705
Philadelphia, Pennsylvania 19104
Austin, Texas 78757
Houston, Texas 77030
Seattle, Washington 98105
More Details
- NCT ID
- NCT07224581
- Status
- Recruiting
- Sponsor
- GRIN Therapeutics, Inc.
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