Trial Review

Technical difficulties have been reported by some users of the search function and is being investigated by technical staff. Thank you for your patience and apologies for any inconvenience caused.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT06392009




Registration number
NCT06392009
Ethics application status
Date submitted
23/04/2024
Date registered
30/04/2024
Date last updated
30/04/2024

Titles & IDs
Public title
A Study of Radiprodil on Safety, Tolerability, Pharmacokinetics, and Effect on Seizures and Behavioral Symptoms in Patients With TSC or FCD Type II
Scientific title
A Multicenter, Open-label Study to Assess the Safety, Tolerability, Pharmacokinetics, and Effect on Seizures and Behavioral Symptoms of Radiprodil in Patients With Tuberous Sclerosis Complex (TSC) or Focal Cortical Dysplasia (FCD) Type II
Secondary ID [1] 0 0
2023-506301-20-00
Secondary ID [2] 0 0
RAD-GRIN-201
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Tuberous Sclerosis Complex 0 0
Focal Cortical Dysplasia 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Neurological 0 0 0 0
Other neurological disorders
Neurological 0 0 0 0
Epilepsy
Mental Health 0 0 0 0
Other mental health disorders

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

Experimental: TSC - 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.

Experimental: FCD Type II - 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.


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), Adverse Drug Reactions (ADRs), TEAEs Leading to Discontinuation and Severity of TEAEs
Timepoint [1] 0 0
from Baseline to End-of-study: 1 year 6 months
Primary outcome [2] 0 0
Plasma concentration of radiprodil and maximum plasma concentration (Cmax)
Timepoint [2] 0 0
Titration Visit 1 (week 7): Pre-dose to 12 hours post-dose. Titration Visits 2,3,4 (week 8 to 13) and Maintenance Visit 7 (week 25): pre-dose to 5 hours post-dose
Primary outcome [3] 0 0
Plasma concentration of radiprodil versus time, area under the curve (AUCt)
Timepoint [3] 0 0
Titration Visit 1 (week 7): Pre-dose to 12 hours post-dose. Titration Visits 2,3,4 (week 8 to 13) and Maintenance Visit 7 (week 25): pre-dose to 5 hours post-dose
Primary outcome [4] 0 0
Pharmacokinetic plasma concentration of radiprodil: half-life (T1/2)
Timepoint [4] 0 0
Titration Visit 1 (week 7): Pre-dose to 12 hours post-dose. Titration Visits 2,3,4 (week 8 to 13) and Maintenance Visit 7 (week 25): pre-dose to 5 hours post-dose
Primary outcome [5] 0 0
Pharmacokinetic plasma concentration of radiprodil: time to Cmax (Tmax)
Timepoint [5] 0 0
Titration Visit 1 (week 7): Pre-dose to 12 hours post-dose. Titration Visits 2,3,4 (week 8 to 13) and Maintenance Visit 7 (week 25): pre-dose to 5 hours post-dose
Primary outcome [6] 0 0
Pharmacokinetic plasma concentration of radiprodil, clearance (Cl)
Timepoint [6] 0 0
Titration Visit 1 (week 7): Pre-dose to 12 hours post-dose. Titration Visits 2,3,4 (week 8 to 13) and Maintenance Visit 7 (week 25): pre-dose to 5 hours post-dose
Primary outcome [7] 0 0
Number of participants with abnormal laboratory tests results
Timepoint [7] 0 0
from Baseline to End-of-study: 1 year 6 months
Primary outcome [8] 0 0
Number of participants with abnormal physical and neurological examination findings
Timepoint [8] 0 0
Baseline, MV7, and in Part B: Month 3, 6, 9, 12: week 6, week 28, week 40, week 52, week 64, week 76
Primary outcome [9] 0 0
Clinically relevant changes in safety parameters: systolic blood pressure
Timepoint [9] 0 0
from Baseline to End-of-study: 1 year 6 months
Primary outcome [10] 0 0
Clinically relevant changes in safety parameters: diastolic blood pressure
Timepoint [10] 0 0
from Baseline to End-of-study: 1 year 6 months
Primary outcome [11] 0 0
Clinically relevant changes in safety parameters: pulse rate
Timepoint [11] 0 0
from Baseline to End-of-study: 1 year 6 months
Primary outcome [12] 0 0
12-Lead ECG: Mean change from Baseline to End-of-Treatment in RR interval
Timepoint [12] 0 0
from Baseline to End-of-study: 1 year 6 months
Primary outcome [13] 0 0
12-Lead ECG: Mean change from Baseline to End-of-Treatment in PR interval
Timepoint [13] 0 0
from Baseline to End-of-study: 1 year 6 months
Primary outcome [14] 0 0
12-Lead ECG: Mean change from Baseline to End-of-Treatment in QRS interval
Timepoint [14] 0 0
from Baseline to End-of-study: 1 year 6 months
Primary outcome [15] 0 0
12-Lead ECG: Mean change from Baseline to End-of-Treatment in QT interval
Timepoint [15] 0 0
from Baseline to End-of-study: 1 year 6 months
Primary outcome [16] 0 0
12-Lead ECG: Mean change from Baseline to End-of-Treatment in QTcF interval
Timepoint [16] 0 0
from Baseline to End-of-study: 1 year 6 months
Secondary outcome [1] 0 0
Percent change from baseline in Video-EEG seizure burden
Timepoint [1] 0 0
Baseline to end-of-treatment: week 6 to week 76
Secondary outcome [2] 0 0
Change from baseline in seizure frequency
Timepoint [2] 0 0
Baseline to Maintenance Visit 7: week 6 to week 25 and Baseline to end-of-treatment: week 6 to week 76
Secondary outcome [3] 0 0
Change from baseline in number of seizure-free days and longest period with no seizures
Timepoint [3] 0 0
Baseline to end-of-treatment: week 6 to week 76
Secondary outcome [4] 0 0
Aberrant Behavior Checklist-Community (ABC-2C)
Timepoint [4] 0 0
Baseline to end-of-treatment: week 6 to week 76
Secondary outcome [5] 0 0
Caregiver Global Impression of Change (CaGI-C)
Timepoint [5] 0 0
Baseline to end-of-treatment: week 6 to week 76
Secondary outcome [6] 0 0
Clinical Global Impression of Change [CGI-C]
Timepoint [6] 0 0
Baseline to end-of-treatment: week 6 to week 76
Secondary outcome [7] 0 0
Pediatric Quality of Life Inventory [PedsQL]
Timepoint [7] 0 0
Baseline to end-of-treatment: week 6 to week 76
Secondary outcome [8] 0 0
Caregiver Burden Inventory (CBI)
Timepoint [8] 0 0
Baseline to end-of-treatment: week 6 to week 76
Secondary outcome [9] 0 0
Columbia-Suicide Severity Rating Scale (C-SSRS)
Timepoint [9] 0 0
Baseline to end-of-treatment: week 6 to week 76

Eligibility
Key inclusion criteria
- Failed to respond to at least 2 anti-seizure medications (ASMs) at appropriate dosages
and duration.

- Disease specific criteria:

1. diagnosis of FCD Type II based on clinical symptoms and confirmed by a positive
magnetic resonance imaging (MRI)

2. diagnosis of TSC by either clinical or genetic diagnostic criteria (Northrup,
2021) as documented in the participant's medical record.

- Participant on average has had at least 8 countable/witnessed primary seizures during
a 4-week baseline period with at least 1 seizure occurring in at least 3 of the 4
weeks of baseline

- All medical interventions for epilepsy / behavior (including ketogenic diet and any
neurostimulation devices) should be stable for 28 days prior to screening with no more
than 6 days per month use of rescue medication. Participants must remain on a stable
regimen throughout the treatment period.

- Participant has had an MRI scan within 12 weeks of screening or during the screening
period.
Minimum age
6 Months
Maximum age
18 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 TSC or FCD Type II that would preclude or jeopardize
participant's safe participation or administration of study drug 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 within 6 months of enrollment for epilepsy or any other
reason.

- Contraindications to radiprodil or with known hypersensitivity to the active substance
or the excipients or other chemically closely related substances.

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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
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
Parallel
Other design features
Phase
Phase 1/Phase 2
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
1/05/2024
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/07/2026
Actual
Sample size
Target
30
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 0 0
Queensland Children Hospital - South Brisbane
Recruitment postcode(s) [1] 0 0
4101 - South Brisbane
Recruitment outside Australia
Country [1] 0 0
Belgium
State/province [1] 0 0
Antwerp
Country [2] 0 0
Belgium
State/province [2] 0 0
Leuven
Country [3] 0 0
Canada
State/province [3] 0 0
Alberta
Country [4] 0 0
Canada
State/province [4] 0 0
Toronto
Country [5] 0 0
Canada
State/province [5] 0 0
Vancouver
Country [6] 0 0
Italy
State/province [6] 0 0
Liguria
Country [7] 0 0
Italy
State/province [7] 0 0
Toscana
Country [8] 0 0
Italy
State/province [8] 0 0
Roma
Country [9] 0 0
Poland
State/province [9] 0 0
Gdansk
Country [10] 0 0
Poland
State/province [10] 0 0
Kraków
Country [11] 0 0
Poland
State/province [11] 0 0
Poznan
Country [12] 0 0
Poland
State/province [12] 0 0
Warszawa
Country [13] 0 0
Spain
State/province [13] 0 0
Barcelona
Country [14] 0 0
Spain
State/province [14] 0 0
Madrid
Country [15] 0 0
United Kingdom
State/province [15] 0 0
Bristol
Country [16] 0 0
United Kingdom
State/province [16] 0 0
Glasgow

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-201 is a phase 1B/2A trial to assess safety, tolerability, pharmacokinetics
(PK), and potential efficacy of radiprodil in participants with Tuberous Sclerosis Complex
(TSC) or Focal Cortical Dysplasia (FCD) type II. 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 and one year in Part B/long-term treatment period. The treatment
period in Part B may be extended based on a favorable benefit/risk profile.
Trial website
https://clinicaltrials.gov/ct2/show/NCT06392009
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
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/NCT06392009