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

NCT05818943 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: RAD-GRIN-1012022-000317-14
• Study Type: interventional
• Target: 24
• Locations: 8 countries
• Sites: 15

Brief 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).

Conditions

GRIN-related Disorders

Keywords

GRIN1; GRIN2A; GRIN2B; GRIN2D

Outcome Measures

Primary Outcomes (6)

• Incidence of Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (SAEs), TEAEs Leading to Discontinuation and Severity of TEAEs

  Frequency, type, severity and duration of adverse events, serious adverse events and adverse drug reactions.

  through study completion (average of 2 years).

• Maximum Plasma concentration of radiprodil (Cmax)

  Titration Visit 1 (week 5): 0,1,2,4,6,8,10,12 hours post-dose. Titration Visits 2,3,4 (week 6 to 11) and Maintenance Visit 4 (week 20): 0,1,2,5 hours post-dose.

• Pharmacokinetic plasma concentration of radiprodil: half-life (T1/2)

  Titration Visit 1 (week 5): 0,1,2,4,6,8,10,12 hours post-dose. Titration Visits 2,3,4 (week 6 to 11) and Maintenance Visit 4 (week 20): 0,1,2,5 hours post-dose.

• Plasma concentration of radiprodil versus time, area under the curve (AUCt)

  Titration Visit 1 (week 5): 0,1,2,4,6,8,10,12 hours post-dose. Titration Visits 2,3,4 (week 6 to 11) and Maintenance Visit 4 (week 20): 0,1,2,5 hours post-dose.

• Pharmacokinetic plasma concentration of radiprodil, clearance (Cl)

  Titration Visit 1 (week 5): 0,1,2,4,6,8,10,12 hours post-dose. Titration Visits 2,3,4 (week 6 to 11) and Maintenance Visit 4 (week 20): 0,1,2,5 hours post-dose.

• Pharmacokinetic plasma concentration of radiprodil, Time corresponding to occurrence of Cmax (Tmax)

  Titration Visit 1 (week 5): 0,1,2,4,6,8,10,12 hours post-dose. Titration Visits 2,3,4 (week 6 to 11) and Maintenance Visit 4 (week 20): 0,1,2,5 hours post-dose.

Secondary Outcomes (10)

• Percent change from baseline in V-EEG seizure burden

  Baseline (week 5) to study completion (average of 2 years).

• Change from baseline in seizure frequency

  Baseline (week 5) to study completion (average of 2 years).

• Aberrant Behavior Checklist-Community (ABC-C)

  Baseline (week 5) to study completion (average of 2 years).

• Caregiver Global Impression of Change (CaGI-C)

  Baseline (week 5) to study completion (average of 2 years).

• Change from Baseline in Clinical Global Impression - Severity [CGI-S]

  Baseline (week 5) to study completion (average of 2 years).

Study Arms (1)

Radiprodil

EXPERIMENTAL

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.

Drug: Radiprodil

Interventions

Radiprodil DRUG

Radiprodil is an orally active, negative allosteric modulator of the NR2B subunit of the NMDA receptor.

Radiprodil

Eligibility Criteria

• Age: 6 Months - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age: ≥6 months to ≤12 years, with GRIN gene variants known to result in GoF of the NMDA receptor.
• Cohort 1 must have at least 1 observable motor seizure per week and ≥4 observable motor seizures (generalized or focal) during the prospective 4-week Observation Period and must have failed to obtain adequate seizure control with at least 2 antiseizure medications (ASMs) used at appropriate dose and duration.
• Cohort 2 must have significant behavioral and/or motor symptoms based on caregiver report with a CGI-S score ≥4.
• Stable antiseizure therapies and nonpharmacological treatments such as ketogenic diet throughout screening and study participation.

You may not qualify if:

• Any other clinically relevant medical, neurologic, or psychiatric condition and/or behavioral disorder unrelated to GRIN-related disorder that would preclude or jeopardize participant's safe participation or the conduct of the study according to the 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 or antagonists of the glutamate receptor, including but not limited to felbamate, memantine, and perampanel.
• Receiving treatment with hormonal therapy such as adrenocorticotrophic hormone or prednisolone.

Sponsors & Collaborators

• GRIN Therapeutics, Inc.: lead

Study Sites (15)

Mid-Atlantic Epilepsy and Sleep Center

Bethesda, Maryland, 20817, United States

Location

Columbia University Irving Medical Center, Dept of Neurology

New York, New York, 10032, United States

Location

Queensland Children's Hospital

South Brisbane, Queensland, 4101, Australia

Location

The Hospital for Sick Children (Sick Kids)

Toronto, Ontario, M5G 1X8, Canada

Location

BC Children's Hospital

Vancouver, BC V6H 3N1, Canada

Location

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

Leipzig, 04103, Germany

Location

KBO-Kinderzentrum München gemeinnützige GmbH

München, 81377, Germany

Location

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

Rome, Lazio, 00165, Italy

Location

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

Florence, Tuscany, 50139, Italy

Location

ERASMUS Medisch Centrum, Developmental & Genetic pediatrics

Rotterdam, 3015, Netherlands

Location

UMC Utrecht - Wilhelmina Kinderziekenhuis, Polikliniek Kinderneurologie

Utrecht, 3508, Netherlands

Location

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

Barcelona, 08950, Spain

Location

Hospital Ruber Internacional

Madrid, 28034, Spain

Location

Royal Hospital for Children Glasgow

Glasgow, G51 4TF, United Kingdom

Location

Great Ormond Street Hospital For Children NHS Foundation Trust

London, WC1N 3JH, United Kingdom

Location

MeSH Terms

Interventions

radiprodil

Study Officials

• Vijay Rai, PhD

  Associate Director of Clinical Operations

  STUDY DIRECTOR

• Michael Panzara, MD, MPH

  Chief Medical Officer

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 22, 2023
• First Posted: April 19, 2023
• Study Start: March 7, 2023
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: November 15, 2024

Record last verified: 2024-11

Locations

DE (2); AU (1); IT (2); NL (2); GB (2); CA (2); ES (2); US (2)