Radiprodil for GRIN Disorders

Recruiting at 14 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

24 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Radiprodil for GRIN disorders?

Research shows that Radiprodil, a drug that targets specific brain receptors, may help treat certain types of epilepsy linked to GRIN2B mutations. This suggests it could be useful for GRIN disorders, as these conditions often involve similar brain receptor issues. ^{1 2 3 4 5}

What is the purpose of this trial?

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 in children with a Gain-of-Function (GoF) genetic variant. The study is open-label, so all participants will be treated with radiprodil. Subjects' participation in the study is expected to last up to six months in Part A. After the end of part A, all participants who are still eligible can choose to continue to receive radiprodil as part of an open-label long-term treatment period (Part B).

Research Team

Vijay Rai, PhD

Principal Investigator

Associate Director of Clinical Operations

Michael Panzara, MD, MPH

Principal Investigator

Chief Medical Officer

Eligibility Criteria

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

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

Treatment Details

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).

Participant Groups

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+

Findings from Research

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]

References

1. England 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. [2020]

2. Switzerland 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. [2023]

3. England pubmed.ncbi.nlm.nih.gov

GRIN2B gain of function mutations are sensitive to radiprodil, a negative allosteric modulator of GluN2B-containing NMDA receptors. [2018]

4. Australia pubmed.ncbi.nlm.nih.gov

Response to growth hormone treatment in Prader-Willi syndrome: auxological criteria versus genetic diagnosis. [2013]

5. Germany pubmed.ncbi.nlm.nih.gov

Evaluation of efficacy and safety of long-acting PEGylated recombinant human growth hormone (Jintrolong) for patients with growth hormone deficiency. [2022]