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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05818943




Registration number
NCT05818943
Ethics application status
Date submitted
22/02/2023
Date registered
19/04/2023

Titles & IDs
Public title
Honeycomb: Evaluation of Radiprodil in Children with GRIN-related Disorder
Scientific title
A Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics, and Effect on Seizures and Behavioral Symptoms of Multiple Individually Titrated Doses of Radiprodil in Children with GRIN-related Disorder
Secondary ID [1] 0 0
2022-000317-14
Secondary ID [2] 0 0
RAD-GRIN-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
GRIN-related Disorders 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Radiprodil

Experimental: Radiprodil - 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.


Treatment: Drugs: Radiprodil
Radiprodil is an orally active, negative allosteric modulator of the NR2B subunit of the NMDA receptor.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (SAEs), TEAEs Leading to Discontinuation and Severity of TEAEs
Timepoint [1] 0 0
through study completion (average of 2 years).
Primary outcome [2] 0 0
Maximum Plasma concentration of radiprodil (Cmax)
Timepoint [2] 0 0
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.
Primary outcome [3] 0 0
Pharmacokinetic plasma concentration of radiprodil: half-life (T1/2)
Timepoint [3] 0 0
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.
Primary outcome [4] 0 0
Plasma concentration of radiprodil versus time, area under the curve (AUCt)
Timepoint [4] 0 0
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.
Primary outcome [5] 0 0
Pharmacokinetic plasma concentration of radiprodil, clearance (Cl)
Timepoint [5] 0 0
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.
Primary outcome [6] 0 0
Pharmacokinetic plasma concentration of radiprodil, Time corresponding to occurrence of Cmax (Tmax)
Timepoint [6] 0 0
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 outcome [1] 0 0
Percent change from baseline in V-EEG seizure burden
Timepoint [1] 0 0
Baseline (week 5) to study completion (average of 2 years).
Secondary outcome [2] 0 0
Change from baseline in seizure frequency
Timepoint [2] 0 0
Baseline (week 5) to study completion (average of 2 years).
Secondary outcome [3] 0 0
Aberrant Behavior Checklist-Community (ABC-C)
Timepoint [3] 0 0
Baseline (week 5) to study completion (average of 2 years).
Secondary outcome [4] 0 0
Caregiver Global Impression of Change (CaGI-C)
Timepoint [4] 0 0
Baseline (week 5) to study completion (average of 2 years).
Secondary outcome [5] 0 0
Change from Baseline in Clinical Global Impression - Severity [CGI-S]
Timepoint [5] 0 0
Baseline (week 5) to study completion (average of 2 years).
Secondary outcome [6] 0 0
Clinical Global Impression of Change [CGI-C]
Timepoint [6] 0 0
Baseline (week 5) to study completion (average of 2 years).
Secondary outcome [7] 0 0
Gross Motor Function Measure (GMFM)
Timepoint [7] 0 0
Baseline (week 5) to study completion (average of 2 years).
Secondary outcome [8] 0 0
Sleep Disturbance Scale for Children (SDSC)
Timepoint [8] 0 0
Baseline (week 5) to study completion (average of 2 years).
Secondary outcome [9] 0 0
Pediatric Quality of Life Inventory [PedsQL]
Timepoint [9] 0 0
Baseline (week 5) to study completion (average of 2 years).
Secondary outcome [10] 0 0
Caregiver Burden Inventory (CBI)
Timepoint [10] 0 0
Baseline (week 5) to study completion (average of 2 years).

Eligibility
Key inclusion criteria
* 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.
Minimum age
6 Months
Maximum age
12 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
7/03/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/11/2026
Actual
Sample size
Target
24
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 0 0
Queensland Children's Hospital - South Brisbane
Recruitment postcode(s) [1] 0 0
4101 - South Brisbane
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Maryland
Country [2] 0 0
United States of America
State/province [2] 0 0
New York
Country [3] 0 0
Canada
State/province [3] 0 0
Ontario
Country [4] 0 0
Canada
State/province [4] 0 0
Vancouver
Country [5] 0 0
Germany
State/province [5] 0 0
Leipzig
Country [6] 0 0
Germany
State/province [6] 0 0
München
Country [7] 0 0
Italy
State/province [7] 0 0
Lazio
Country [8] 0 0
Italy
State/province [8] 0 0
Toscana
Country [9] 0 0
Netherlands
State/province [9] 0 0
Rotterdam
Country [10] 0 0
Netherlands
State/province [10] 0 0
Utrecht
Country [11] 0 0
Spain
State/province [11] 0 0
Barcelona
Country [12] 0 0
Spain
State/province [12] 0 0
Madrid
Country [13] 0 0
United Kingdom
State/province [13] 0 0
Glasgow
Country [14] 0 0
United Kingdom
State/province [14] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
GRIN Therapeutics, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Vijay Rai, PhD
Address 0 0
Associate Director of Clinical Operations
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Clinical operations
Address 0 0
Country 0 0
Phone 0 0
+1-877-225-0014
Fax 0 0
Email 0 0
ClinicalTrials@GrinTherapeutics.com
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Undecided
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05818943