Share
Save
Honeycomb: Evaluation of Radiprodil in Children with GRIN-related Disorder
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).
Study details:
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:. * Screening/Observation Period (35 days): Investigators assess eligibility followed by a four(4)- week Observation Period to evaluate seizure frequency and/or behavioral symptoms. * Titration Period (approx.
51 days): Overnight stay to administer radiprodil twice daily to assigned dose level, assessing plasma concentrations, safety, and tolerability during the titration period. Once a safe and potentially effective dose has been established, the participant will immediately enter the Maintenance Period. * Maintenance Period (up to 53 days): During the Maintenance Period, the participant will continue to take the highest safe and potentially effective dose, as identified during the Titration Period.
At the end of the Maintenance Period, there will be an additional overnight stay when the participant will either be invited to take part in Part B or enter the Tapering and Safety Follow-up Period. * Tapering (15 days) and Safety Follow-up Period (14 days): the participant who doesn't take part in the long-term treatment period (Part B) will need to taper off (ie gradually decrease) the study medicine for 15 days and enter a safety Follow-up Period (14 days). In this case, the participant will make one (1) last visit to the study site 14 days after his/her last dose of radiprodil.
PART B:. * Long-Term Treatment Period (not specified): Participation in Part B of the study, at the dose established during part A, will be continued until such time as either the participant withdraws/is withdrawn from the study or sponsor terminates the study. During this period there will be four (4) visits per year, two(2) of which will require overnight stays.
At the end of the Long-Term Treatment Period, the participant will enter the Tapering and Safety Follow-up Period. * Tapering (15 days) and Safety Follow-up Period (14 days): the participant will need to taper off the study medicine for 15 days and enter a safety Follow-up Period of 14 days. In this case, the participant will make one (1) last visit to the study site 14 days after his/her last dose of radiprodil.
Eligibility criteria
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
Inclusion criteria
Exclusion criteria
Eligibility
Age eligible for study : 6 and older
Healthy volunteers accepted : No
Gender eligible for study: All
Things to know
Study dates
Study start: 2023-03-07
Primary completion: 2026-11-01
Study completion finish: 2026-11-01
Study type
TREATMENT
Phase
PHASE1
Trial ID
NCT05818943
Intervention or treatment
DRUG: Radiprodil
Conditions
- • GRIN-related Disorders
Find a site
Closest Location:
Queensland Children's Hospital
Research sites nearby
Select from list below to view details:
Queensland Children's Hospital
South Brisbane, Queensland, Australia
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
| Participant Group/Arm | Intervention/Treatment |
|---|---|
EXPERIMENTAL: Radiprodil
| DRUG: Radiprodil
|
What is the study measuring?
Primary outcome
| Primary Outcome Measure | Primary Outcome Description | Primary Outcome Time Frame |
|---|---|---|
| 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) | Not Specified | 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) | Not Specified | 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) | Not Specified | 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) | Not Specified | 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) | Not Specified | 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
| Secondary Outcome Measure | Secondary Outcome Description | Secondary Outcome Time Frame |
|---|---|---|
| Percent change from baseline in V-EEG seizure burden | Assessed by 8- to 24- hour video electroencephalogram | Baseline (week 5) to study completion (average of 2 years). |
| Change from baseline in seizure frequency | Assessed by seizure diaries | 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. | 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). | 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"). | 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"). | 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. | 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. | 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. | 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. | Baseline (week 5) to study completion (average of 2 years). |
Frequently Asked Questions
Please note: some questions and answers are submitted by anonymous patients or using AI, and have not been verified by Clinrol
No questions submitted. Be the first to ask a question!