2A- 2B- of 2D-genes
Conditions
Interventions
The pediatric radiprodil formulation used in this study is an oral suspension
obtained by reconstitution of dispersible granules with a diluent. The oral
suspension will be prepared extemporaneously
Sponsors
GRIN Therapeutics, Inc.
Eligibility
Age
No minimum to 15 Years
Inclusion criteria
Inclusion criteria: Inclusion criteria: For Part A and Part B (unless stated otherwise): 1. For Part A, pediatric participants aged >=6 months to =6 months with GRIN 1, 2A, 2B, or 2D gene variants known to result in GoF of the NMDA receptor. 2. Participant to be enrolled in the first cohort experiences the following (Part A only): a) At least 1 observable motor seizure per week and >=4 observable motor seizures (generalized or focal) during the prospective 4-week Observation Period. b) Has failed to obtain adequate seizure control with at least 2 ASMs used at appropriate dose and duration with assured medication adherence (if applicable). 3. Participant to be enrolled in the second cohort experiences the following (Part A only): a) Significant behavioral and/or motor symptoms based on caregiver report with a CGI-S score >=4 at the Screening Visit and Day -1 of Visit T1. 4. For part A, current therapies need to be on a stable dose for at least 4 weeks prior to Screening and should be maintained stable throughout the whole study duration, nonpharmacological treatments such as ketogenic diet should be kept as stable as possible during screening and participation in the study. Changes in antiseizure medication should be discussed with the sponsor in consultation with the investigator. For all inclusion criteria see Protocol. Rescreening criteria for Part B only: 1. Participant has received at least 8 weeks of treatment (combined Titration and Maintenance Period) with radiprodil during Part A. 2. The benefit-risk of continuing radiprodil treatment remains favorable as determined by the investigator*s clinical assessment and is eligible to continue treatment according to the judgement of the investigator.
Exclusion criteria
Exclusion criteria: Exclusion criteria (at initial Screening and following completion of the Maintenance Period of Part A, unless stated otherwise): 1. Participant with any other clinically relevant medical, neurologic, or psychiatric condition and/or behavioral disorder unrelated to GRIN related disorders 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. 2. Participant with a body weight
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| • Adverse events (AEs), serious adverse events (SAEs), and adverse drug reactions (ADRs) (frequency, type, severity, and duration) • Changes in vital signs • Physical examination findings • 12-lead electrocardiogram (ECG) findings • Clinically significant changes in laboratory parameters • Emergence of new seizure types • Occurrence of suicidal ideation or behavior • Determination of the maximum tolerated dose of radiprodil based on safety and tolerability data • Plasma concentrations of radiprodil at predefined timepoints | — |
Secondary
| Measure | Time frame |
|---|---|
| • Change from Baseline to end of treatment in seizure frequency from daily seizure electronic diary (eDiary) • Percent change from Baseline to end of treatment in video electroencephalogram (V EEG) seizure burden (e.g., seizure type, severity, and frequency recorded during V EEGs) • Seizure free days and longest period with no seizures Change from Baseline to end of treatment in seizure frequency from daily seizure electronic diary (eDiary) • Percent change from Baseline to end of treatment in video electroencephalogram (V EEG) seizure burden (e.g., seizure type, severity, and frequency recorded during V EEGs) • Seizure free days and longest period with no seizures • Change from Baseline to end of treatment in behavioral features as measured by Vineland adaptive behavioral scale (VABS), Bayley scale of infant development (BSID), and the aberrant behavior checklist-community (ABC-C), as well as other disorder features as measured by gross motor function measure (GMFM), sleep disturbance scale for children (SDSC), quality of life (Pediatric Quality of Life Inventory [PedsQL]), Caregiver Burden Inventory (CBI),and global impression (Caregiver Global Impression of Change [CaGI C] evaluating seizures, behavioral symptoms and overall condition),]), and Clinical Global Impression of Change [CGI-C] scales) • Plasma concentrations of the 2 major metabolites of radiprodil | — |
Countries
Netherlands
Outcome results
None listed