A Phase 1 interventional study of Radiprodil in GRIN-related Disorders, sponsored by GRIN Therapeutics, Inc.. Active, not recruiting at 15 sites in 8 countries. Open to participants aged 6 Months to 12 Years. Per ClinicalTrials.gov, last updated 2024-11-15.
Sponsored by GRIN Therapeutics, Inc. · Phase 1, Interventional, and Treatment
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).
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:
PART B:
GRIN Therapeutics, Inc. is the lead sponsor of 6 studies on the registry; 2 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
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
Radiprodil is an orally active, negative allosteric modulator of the NR2B subunit of the NMDA receptor.
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.
Time frame: through study completion (average of 2 years).
Maximum Plasma concentration of radiprodil (Cmax)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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.
Percent change from baseline in V-EEG seizure burden
Assessed by 8- to 24- hour video electroencephalogram
Time frame: Baseline (week 5) to study completion (average of 2 years).
Change from baseline in seizure frequency
Assessed by seizure diaries
Time frame: Baseline (week 5) to study completion (average of 2 years).
Aberrant Behavior Checklist-Community (ABC-C)
The ABCC is a standardized 58-item caregiver-reported problem-behavior rating scale, originally designed to assess treatment effects in people with intellectual disabilities. Each item is scored from 0 (never a problem) to 3 (severe problem). Items load onto one of five empirically derived subscales: Irritability, Agitation, \& Crying (15 items); Lethargy/Social Withdrawal (16 items); Stereotypic Behavior (7 items); Hyperactivity/Noncompliance (16 items); and Inappropriate Speech (4 items). A total score would range from 0 to 174.
Time frame: Baseline (week 5) to study completion (average of 2 years).
Caregiver Global Impression of Change (CaGI-C)
The CaGI-C is a 7-point caregiver-rated scale ranging from 1 (very much improved) to 7 (very much worse).
Time frame: Baseline (week 5) to study completion (average of 2 years).
Change from Baseline in Clinical Global Impression - Severity [CGI-S]
The CGI-S scale is a clinician-rated measures of severity of a symptom or condition, using a single item, 6- or 7-point scale. The CGI-S scale ranges from 1 ("None") to 6 ("Very Severe").
Time frame: Baseline (week 5) to study completion (average of 2 years).
Clinical Global Impression of Change [CGI-C]
The CGI scale is a clinician-rated measures of change of a symptom or condition, using a single item, 6- or 7-point scale. The CGI-C scale ranges from 1 ("Very much worse") to 7 ("Very much improved").
Time frame: Baseline (week 5) to study completion (average of 2 years).
Gross Motor Function Measure (GMFM)
The GMFM is a standardized observational instrument designed and validated to measure change in gross motor function over time in children with cerebral palsy. There is a 4-point (0 to 3) scoring system for each of the 5 dimensions of gross motor function, with higher scores denoting better performance.
Time frame: Baseline (week 5) to study completion (average of 2 years).
Sleep Disturbance Scale for Children (SDSC)
The SDSC is a parent-report measure to screen for sleep disturbances within the preceding period. It is a 27-item questionnaire rated on a 5-point Likert scale, with higher scores being indicative of more acute sleep disturbances.
Time frame: Baseline (week 5) to study completion (average of 2 years).
Pediatric Quality of Life Inventory [PedsQL]
The PedsQL is a 23-item generic health status instrument assessing 5 domains of health in children. It's a 0-100 scale, and higher scores are indicative of better health-related quality of life.
Time frame: Baseline (week 5) to study completion (average of 2 years).
Caregiver Burden Inventory (CBI)
The CBI is a validated scale providing information regarding the impact of caregiving on the lives of caregivers. It comprises 24 closed questions divided into 5 dimensions. Each dimension includes 4 or 5 items. Each item is given a score between 0 and 4, where higher scores indicate greater caregiver burden.
Time frame: Baseline (week 5) to study completion (average of 2 years).
Plan to share: Undecided
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This study is active, not recruiting, as verified in Nov 2024. You cannot join it, but the record below documents what was studied.
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GRIN Therapeutics, Inc.