Radiprodil for GRIN Disorders

Not currently recruiting at 16 trial locations

Overseen By Clinical operations

Age: < 18

Sex: Any

Trial Phase: Phase 1

Sponsor: GRIN Therapeutics, Inc.

Must be taking: Antiseizure medications

Must not be taking: Glutamate drugs, Hormonal therapy

Disqualifiers: Severe hepatic dysfunction, Brain surgery, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 7

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test radiprodil for children with a GRIN-related disorder, a genetic condition that can cause seizures or significant behavior and movement challenges. The main goal is to determine if radiprodil is safe and effective for these children. The trial is open-label, so everyone will receive the treatment. Children with frequent seizures or noticeable behavioral issues who have not found success with other treatments might be suitable candidates. Participants will take radiprodil for up to six months, with an option to continue long-term if eligible. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial requires that you stay on stable antiseizure therapies and non-drug treatments like a ketogenic diet. However, you cannot take certain drugs like felbamate, memantine, perampanel, or hormonal therapies like prednisolone.

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

Research has shown that radiprodil was well tolerated in previous studies. It was linked to a significant reduction in seizure frequency for children with GRIN disorders. In earlier trials, radiprodil showed promising results without major safety concerns. Participants found it easy to use, and serious side effects were not commonly reported. Although this trial is in an early stage, safety remains a key focus. Data from past studies suggest that radiprodil is generally safe for people. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Radiprodil is unique because it targets GRIN disorders with a novel mechanism of action. Unlike traditional treatments that might focus on managing symptoms, Radiprodil directly modulates NMDA receptors, which are crucial for brain signaling and function. This targeted approach could potentially lead to more effective management of GRIN disorders by directly addressing the underlying receptor dysfunction. Researchers are excited because this could mean improved outcomes and quality of life for patients with these challenging conditions.

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

Research has shown that radiprodil, the investigational treatment in this trial, may help treat GRIN-related disorders by reducing seizures. Studies have found that radiprodil is safe for children with these disorders. It calms overactive brain signals that can cause seizures. Although more research is needed, these early results suggest that radiprodil could help manage symptoms of GRIN disorders. ^{1 2 4 6 7}

Who Is on the Research Team?

Vijay Rai, PhD

Principal Investigator

Associate Director of Clinical Operations

Michael Panzara, MD, MPH

Principal Investigator

Chief Medical Officer

Are You a Good Fit for This Trial?

This trial is for children aged 6 months to 12 years with GRIN gene variants causing overactive NMDA receptors. Participants must have frequent motor seizures or significant behavioral/motor symptoms despite previous treatments. They should be on stable seizure therapies during the study.

Inclusion Criteria

Cohort 2 must have significant behavioral and/or motor symptoms based on caregiver report with a CGI-S score ≥4

My seizure treatments have been stable, including any diets like ketogenic.

I am between 6 months and 12 years old with a GRIN gene variant affecting the NMDA receptor.

Exclusion Criteria

Clinically significant laboratory or ECG abnormalities

My liver is not working well (severe issues).

I am currently on hormonal therapy like ACTH or prednisolone.

Timeline for a Trial Participant

Screening/Observation

Participants are screened for eligibility to participate in the trial

5 weeks

1 visit (in-person)

Titration

Overnight stay to administer radiprodil twice daily to assigned dose level, assessing plasma concentrations, safety, and tolerability

7 weeks

Overnight stay

Maintenance

Participants continue to take the highest safe and potentially effective dose, as identified during the Titration Period

7.5 weeks

1 visit (in-person)

Tapering and Safety Follow-up

Participants taper off the study medicine and enter a safety follow-up period

4 weeks

1 visit (in-person)

Long-Term Treatment (Part B)

Participants continue treatment in an open-label long-term period until withdrawal or study termination

4 visits per year, 2 overnight stays

What Are the Treatments Tested in This Trial?

Interventions

• Radiprodil

Trial Overview The trial tests Radiprodil's safety, tolerability, and potential effectiveness in treating GRIN-related disorders in kids. It's an open-label phase 1B study where all participants receive the drug, first in a six-month period (Part A), then possibly longer-term (Part B).

How Is the Trial Designed?

Group I: Radiprodil Experimental Treatment 1 Intervention

Liquid suspension of radiprodil, at concentrations 0.25 mg/mL or 2.50 mg/mL for 1% and 10% formulation respectively. It will be administered twice a day (bid) either orally or via gastric or nasogastric tube, slowly up-titrated to the highest tolerated dose.

Who Is Running the Clinical Trial?

GRIN Therapeutics, Inc.

Lead Sponsor

Trials

2

Recruited

50+

Published Research Related to This Trial

A Phase III study involving 34 infants and toddlers with Prader-Willi syndrome showed that 52 weeks of treatment with recombinant human growth hormone (Eutropin) significantly improved growth and body composition, with increases in height and lean body mass similar to those seen with the comparator treatment (Genotropin).

Both Eutropin and Genotropin treatments led to improvements in motor and cognitive development, and the safety profiles were comparable, indicating that Eutropin is a safe and effective option for young patients with Prader-Willi syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of recombinant human growth hormone treatment on growth, body composition, and safety in infants or toddlers with Prader-Willi syndrome: a randomized, active-controlled trial. Yang, A., Choi, JH., Sohn, YB., et al.[2020]

A 52-week treatment with recombinant human growth hormone (rhGH) significantly improved height, body weight, and BMI in 35 infants and young children with Prader-Willi syndrome (PWS), indicating its efficacy in promoting growth.

The treatment also enhanced mental development, particularly in children under 9 months old, and helped slow the decline in motor function, suggesting that earlier intervention may lead to better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early recombinant human growth hormone treatment improves mental development and alleviates deterioration of motor function in infants and young children with Prader-Willi syndrome. Cheng, RQ., Ying, YQ., Qiu, ZQ., et al.[2023]

Citations

1. 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- ... The BeeLine trial is a placebo-controlled study designed to evaluate radiprodil's impact on both seizure frequency and non-seizure symptoms ...

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

Radiprodil Designated a Breakthrough Therapy for GRIN ... Radiprodil treatment was well tolerated and associated with significant reductions in seizure frequency for children with GRIN disorders.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05818943

NCT05818943 | Honeycomb: Evaluation of Radiprodil in ... Study RAD-GRIN-101 is a phase 1B trial to assess safety, tolerability, PK, and potential efficacy of radiprodil for the treatment of GRIN-related disorder ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38529699/

Radiprodil, a selective GluN2B negative allosteric ... Our data clearly show that radiprodil, a GluN2B selective negative allosteric modulator, may have the potential to control seizures in patients with GRIN2A GoF ...

5. clinicaltrials.eu clinicaltrials.eu/inn/radiprodil/

Radiprodil: A Promising New Drug for Neurological Disorders Radiprodil is an experimental drug being studied in clinical trials for various neurological conditions, including GRIN-related disorders, infantile spasms, ...

6. academic.oup.com academic.oup.com/brain/advance-article-pdf/doi/10.1093/brain/awaf355/64378943/awaf355.pdf

receptors by radiprodil - ACCEPTED MANUSCRIPT These data. 5 suggest that the adult heterozygous GluN2B-S810R mice have a higher seizure susceptibility. 6. (i.e., a reduced seizure threshold). 7. We next ...

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 ... The Astroscape trial is designed to evaluate the safety of radiprodil as a potential treatment for seizures and for a range of nonseizure ...