Radiprodil for Neurodevelopmental Disorder

Recruiting at 19 trial locations

Overseen By Clinical Operations

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: GRIN Therapeutics, Inc.

Must be taking: Antiseizure medications

Must not be taking: More than 4 ASMs

Disqualifiers: Clinically relevant conditions, weight <5 kg, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness and safety of radiprodil for individuals with GRIN-related neurodevelopmental disorder (GRIN-NDD), which includes movement issues and other symptoms due to specific genetic changes. The study consists of two groups: one with participants experiencing frequent motor seizures and another with fewer or no seizures but still significant symptoms. The trial compares radiprodil to a placebo to determine its impact on seizures and other symptoms. Participants who have tried at least two other seizure medications without success might be suitable for this study. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking treatment advancements.

Do I have to stop taking my current medications for the trial?

You will need to stay on a stable dose of your current antiseizure medications and any non-drug treatments like a ketogenic diet throughout the study. The trial does not require you to stop taking your current medications.

Is there any evidence suggesting that radiprodil is likely to be safe for humans?

Earlier studies found radiprodil to be well-tolerated, with few serious side effects. The Honeycomb trial showed that radiprodil was generally safe for participants. Additionally, there were indications that it might help reduce seizures, a key aspect of the condition under study. While new trials may yield different results, the earlier findings are promising regarding safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Radiprodil is unique because it offers a new approach to treating neurodevelopmental disorders by targeting specific receptors in the brain known as NMDA receptors. Unlike traditional treatments that often focus on general symptom management, Radiprodil specifically modulates these receptors to potentially improve cognitive and behavioral outcomes. Researchers are excited about this treatment because it promises a more targeted and effective intervention, which could lead to better results with fewer side effects compared to current therapies.

What evidence suggests that radiprodil might be an effective treatment for GRIN-related neurodevelopmental disorder?

Research has shown that radiprodil, which participants in this trial may receive, can greatly reduce seizures in people with GRIN-related neurodevelopmental disorders. In earlier studies, patients who took radiprodil experienced an 86% decrease in seizure frequency. Specifically, most patients had fewer seizures after starting the treatment, with 71% of those treated showing this improvement. These findings suggest that radiprodil could help manage seizures in GRIN-related conditions. ^{1 2 3 6 7}

Who Is on the Research Team?

Alex Cepeda

Principal Investigator

GRIN Therapeutics, Inc.

Russel Chin

Principal Investigator

GRIN Therapeutics, Inc.

Are You a Good Fit for This Trial?

This trial is for individuals with GRIN-related neurodevelopmental disorder (GRIN-NDD) who have a gain-of-function genetic variant. There are two groups: one with regular motor seizures and another with symptoms but fewer or no seizures. Participants must not be part of other studies, should be able to swallow tablets, and need a caregiver's consent if under legal age.

Inclusion Criteria

Part B: Participant has completed Part A and is eligible to continue study participation according to the judgement of the investigator and sponsor.

I have severe neurodevelopmental symptoms with a GRIN-CGI-S score of 4 or higher.

I have been on a stable dose of my seizure medication for at least 4 weeks.

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

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.

I am taking more than 4 seizure medications.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

Titration

Titration of radiprodil or placebo to target dose

4 weeks

4 visits (in-person)

Maintenance

Target dose of radiprodil or placebo maintained

12 weeks for Cohort 1, 24 weeks for Cohort 2

Tapering and Follow-up

Gradual decrease and follow-up observation period for participants not entering Part B

Open-label Extension

Participants will continue to receive radiprodil until withdrawal, study termination, or market access

Tapering and Follow-up

Gradual decrease and follow-up observation period for participants upon leaving the study

What Are the Treatments Tested in This Trial?

Interventions

• Radiprodil

Trial Overview The study tests Radiprodil against a placebo in two parts: first, participants are randomly given either the drug or placebo; second, after this phase ends, they can all receive Radiprodil in an open-label extension. The trial measures how well Radiprodil works on both seizure and non-seizure symptoms over different lengths of time for each group.

How Is the Trial Designed?

Group I: Radiprodil Experimental Treatment 1 Intervention

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.

Group II: Placebo Placebo Group 1 Intervention

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

Who Is Running the Clinical Trial?

GRIN Therapeutics, Inc.

Lead Sponsor

Trials

2

Recruited

50+

Aziende Chimiche Riunite Angelini Francesco S.p.A

Industry Sponsor

Trials

37

Recruited

5,700+

Citations

1. practicalneurology.com practicalneurology.com/news/radiprodil-designated-a-breakthrough-therapy-for-grin-related-neurodevelopmental-disorder/2473793/

Radiprodil Designated a Breakthrough Therapy for GRIN ... Treatment with radiprodil was associated with an 86% reduction from baseline in countable motor seizures (CMS). 71% of radiprodil-treated ...

2. prnewswire.com prnewswire.com/news-releases/grin-therapeutics-announces-positive-topline-data-from-honeycomb-trial-of-radiprodil-in-grin-related-neurodevelopmental-disorder-302240847.html

GRIN Therapeutics Announces Positive Topline Data from ... During Part A of the study, patients treated with radiprodil showed a median reduction of 86% in seizure frequency versus baseline, which was a ...

3. aesnet.org aesnet.org/abstractslisting/pharmacokinetics-safety-tolerability-and-effect-on-seizure-frequency-and-behavior-of-individually-titrated-radiprodil-doses-in-children-with-grin-related-disorder-top-line-multicenter-study-data

Abstracts - American Epilepsy Society Conclusions: Radiprodil appears to be well-tolerated to date with potential signs of meaningful clinical effects in this severe disorder with ...

4. neurologylive.com neurologylive.com/view/phase-3-beeline-trial-to-evaluate-radiprodil-in-grin-related-neurodevelopmental-disorder

Phase 3 BeeLine Trial to Evaluate Radiprodil in GRIN- ... In Honeycomb, treatment with radiprodil resulted in a median reduction of 86% in seizure frequency relative to baseline, with 71% of patients ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT07224581

NCT07224581 | Beeline: A Phase 3 Study in GRIN-related ... This study will enroll two cohorts: one cohort of participants with a minimal number of countable motor seizures (with or without behavioral ...

6. grintherapeutics.com grintherapeutics.com/

GRIN Therapeutics – Advancing a targeted approach to the ... GRIN Therapeutics to Present Data from Honeycomb Trial of Investigational Radiprodil in GRIN-Related Neurodevelopmental Disorder.

7. prnewswire.com prnewswire.com/news-releases/grin-therapeutics-presents-multiple-clinical-development-updates-for-radiprodil-at-2025-ilae-international-epilepsy-congress-302541483.html

GRIN Therapeutics Presents Multiple Clinical Development ... In the Phase 1b Honeycomb trial, radiprodil was found to be generally well tolerated and associated with a substantial reduction in seizure ...