Honeycomb: Evaluation of Radiprodil in Children with GRIN-related Disorder

Last updated: November 13, 2024
Sponsor: GRIN Therapeutics, Inc.
Overall Status: Active - Not Recruiting

Phase

1

Condition

N/A

Treatment

Radiprodil

Clinical Study ID

NCT05818943
RAD-GRIN-101
2022-000317-14
  • Ages 6-12
  • All Genders

Study Summary

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).

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Age: ≥6 months to ≤12 years, with GRIN gene variants known to result in GoF of theNMDA receptor.

  • Cohort 1 must have at least 1 observable motor seizure per week and ≥4 observablemotor seizures (generalized or focal) during the prospective 4-week ObservationPeriod and must have failed to obtain adequate seizure control with at least 2antiseizure medications (ASMs) used at appropriate dose and duration.

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

  • Stable antiseizure therapies and nonpharmacological treatments such as ketogenicdiet throughout screening and study participation.

Exclusion

Exclusion Criteria:

  • Any other clinically relevant medical, neurologic, or psychiatric condition and/orbehavioral disorder unrelated to GRIN-related disorder that would preclude orjeopardize participant's safe participation or the conduct of the study according tothe judgement of the investigator.

  • Clinically significant laboratory or ECG abnormalities.

  • Severe hepatic dysfunction (Child-Pugh grade C).

  • History of brain surgery for epilepsy or any other reason.

  • Receiving treatment with contraindicated concomitant drugs such as agonists orantagonists of the glutamate receptor, including but not limited to felbamate,memantine, and perampanel.

  • Receiving treatment with hormonal therapy such as adrenocorticotrophic hormone orprednisolone.

Study Design

Total Participants: 24
Treatment Group(s): 1
Primary Treatment: Radiprodil
Phase: 1
Study Start date:
March 07, 2023
Estimated Completion Date:
November 30, 2026

Study Description

The effect of radiprodil is assessed in two (2) cohorts of pediatric participants: one (1) cohort of participants with treatment-resistant seizures (with or without behavioral symptoms) (Cohort 1) and one (1) cohort of participants with behavioral symptoms but no qualifying seizures (Cohort 2) caused by Gain-of-Function (GoF) variants in the GRIN gene. As the daily doses of radiprodil will be individually titrated for every participant and all the participants will receive the study drug, this is in effect a "single group" study.

This study is divided into the following periods:

PART A:

  • Screening/Observation Period (35 days): Investigators assess eligibility followed by a four(4)- week Observation Period to evaluate seizure frequency and/or behavioral symptoms.

  • Titration Period (approx. 51 days): Overnight stay to administer radiprodil twice daily to assigned dose level, assessing plasma concentrations, safety, and tolerability during the titration period. Once a safe and potentially effective dose has been established, the participant will immediately enter the Maintenance Period.

  • Maintenance Period (up to 53 days): During the Maintenance Period, the participant will continue to take the highest safe and potentially effective dose, as identified during the Titration Period. At the end of the Maintenance Period, there will be an additional overnight stay when the participant will either be invited to take part in Part B or enter the Tapering and Safety Follow-up Period.

  • Tapering (15 days) and Safety Follow-up Period (14 days): the participant who doesn't take part in the long-term treatment period (Part B) will need to taper off (ie gradually decrease) the study medicine for 15 days and enter a safety Follow-up Period (14 days). In this case, the participant will make one (1) last visit to the study site 14 days after his/her last dose of radiprodil.

PART B:

  • Long-Term Treatment Period (not specified): Participation in Part B of the study, at the dose established during part A, will be continued until such time as either the participant withdraws/is withdrawn from the study or sponsor terminates the study. During this period there will be four (4) visits per year, two(2) of which will require overnight stays. At the end of the Long-Term Treatment Period, the participant will enter the Tapering and Safety Follow-up Period.

  • Tapering (15 days) and Safety Follow-up Period (14 days): the participant will need to taper off the study medicine for 15 days and enter a safety Follow-up Period of 14 days. In this case, the participant will make one (1) last visit to the study site 14 days after his/her last dose of radiprodil.

Connect with a study center

  • Queensland Children's Hospital

    South Brisbane, Queensland 4101
    Australia

    Site Not Available

  • The Hospital for Sick Children (Sick Kids)

    Toronto, Ontario M5G 1X8
    Canada

    Site Not Available

  • BC Children's Hospital

    Vancouver, BC V6H 3N1
    Canada

    Site Not Available

  • Abteilung für Neuropädiatrie, Klinik und Poliklinik für Kinder - und Jugendmedizin, Universitätsklinikum Leipzig

    Leipzig, 04103
    Germany

    Site Not Available

  • KBO-Kinderzentrum München gemeinnützige GmbH

    München, 81377
    Germany

    Site Not Available

  • Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Ospedale Pediatrico Bambino Gesu

    Roma, Lazio 00165
    Italy

    Site Not Available

  • Azienda Ospedaliero Universitaria Careggi (AOUC) Firenze - Azienda Ospedaliera Universitaria Meyer

    Firenze, Toscana 50139
    Italy

    Site Not Available

  • ERASMUS Medisch Centrum, Developmental & Genetic pediatrics

    Rotterdam, 3015
    Netherlands

    Site Not Available

  • UMC Utrecht - Wilhelmina Kinderziekenhuis, Polikliniek Kinderneurologie

    Utrecht, 3508
    Netherlands

    Site Not Available

  • Universitat de Barcelona - Hospital Sant Joan de Deu Barcelona (HSJDB)

    Barcelona, 08950
    Spain

    Site Not Available

  • Hospital Ruber Internacional

    Madrid, 28034
    Spain

    Site Not Available

  • Royal Hospital for Children Glasgow

    Glasgow, G51 4TF
    United Kingdom

    Site Not Available

  • Great Ormond Street Hospital For Children NHS Foundation Trust

    London, WC1N 3JH
    United Kingdom

    Site Not Available

  • Mid-Atlantic Epilepsy and Sleep Center

    Bethesda, Maryland 20817
    United States

    Site Not Available

  • Columbia University Irving Medical Center, Dept of Neurology

    New York, New York 10032
    United States

    Site Not Available

Not the study for you?

Let us help you find the best match. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.