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

GRIN Therapeutics

Status and phase: Enrolling; Phase 3

Conditions: GRIN-related Neurodevelopmental Disorder

Treatments: Drug: Placebo; Drug: Radiprodil

Study type: Interventional

Funder types: Industry

Identifiers

NCT07224581

Beeline RAD-GRIN-101

Details and patient eligibility

About

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.

Full 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

Enrollment: 100 estimated patients

Sex: All

Ages: 1 month to 18 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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100 participants in 2 patient groups, including a placebo group

Radiprodil

Experimental group

Description:

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.

Treatment:

Drug: Radiprodil

Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo