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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05818943




Registration number
NCT05818943
Ethics application status
Date submitted
22/02/2023
Date registered
19/04/2023
Date last updated
17/04/2024

Titles & IDs
Public title
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
N/A
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
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
1/11/2025
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
Canada
State/province [1] 0 0
Ontario
Country [2] 0 0
Canada
State/province [2] 0 0
Vancouver
Country [3] 0 0
Germany
State/province [3] 0 0
Leipzig
Country [4] 0 0
Germany
State/province [4] 0 0
München
Country [5] 0 0
Italy
State/province [5] 0 0
Lazio
Country [6] 0 0
Italy
State/province [6] 0 0
Toscana
Country [7] 0 0
Netherlands
State/province [7] 0 0
Rotterdam
Country [8] 0 0
Netherlands
State/province [8] 0 0
Utrecht
Country [9] 0 0
Spain
State/province [9] 0 0
Barcelona
Country [10] 0 0
Spain
State/province [10] 0 0
Madrid
Country [11] 0 0
United Kingdom
State/province [11] 0 0
Glasgow
Country [12] 0 0
United Kingdom
State/province [12] 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
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).
Trial website
https://clinicaltrials.gov/ct2/show/NCT05818943
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



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05818943