A Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics,and Effect on Seizures and Behavioral Symptoms of Multiple IndividuallyTitrated Doses of Radiprodil in Children with GRIN-related Disorder
- Conditions
- GRIN-related disorderMedDRA version: 26.0Level: PTClassification code: 10064062Term: Neurodevelopmental disorder Class: 100000004873Therapeutic area: Diseases [C] - Nervous System Diseases [C10]
- Registration Number
- CTIS2023-509672-42-00
- Lead Sponsor
- Grin Therapeutics Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 25
For Part A and Part B (unless stated otherwise): 1. For Part A, pediatric participants aged =6 months to =12 years with GRIN 1, 2A, 2B, or 2D gene variants known to result in GoF of the NMDA receptor. For Part B, pediatric participants aged =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. 5. Participant's caregivers have signed informed consent and participant has signed assent (if applicable). 6. Participant's caregivers are willing and able to complete entries in the eDiary on a daily basis. 7. Participant is 1 of the following: a. Not of childbearing potential (premenarchal or male/not in possession of a uterus). b. If of childbearing potential, is nonpregnant (negative serum pregnancy test results at Screening), nonlactating, and practicing 1 of the following medically acceptable methods of birth control: • Abstinence from heterosexual intercourse as a lifestyle choice. • Hormonal methods such as oral, implantable, injectable, or transdermal contraceptives for a minimum of 1 full cycle (based on the participant's usual menstrual cycle period) before IP administration. • Intrauterine device. c. If male, is willing to use a highly effective method of contraception throughout the study period. 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 (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 GRINrelated 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 <10 kg on Day -1 of Visit T1 for whom a gastric tube is the only possibility for radiprodil dosing (during treatment with the first dose in Part A only). 3. Participant with any clinically significant laboratory or ECG abnormalities. 4. Participant has severe hepatic dysfunction (Child-Pugh grade C). 5. Participant has a history of brain surgery for epilepsy or any other reason. 6. Participant with any contraindications to radiprodil or with known hypersensitivity to the active substance or the excipients or other chemically closely related substances. 7. Participant receiving treatment with contraindicated concomitant drugs such as agonists or antagonists of the glutamate receptor, including but not limited to lamotrigine, felbamate, memantine, and perampanel. 8. Participant is on treatment with hormonal therapy such as adrenocorticotrophic hormone or prednisolone (Part A only). 9. Participant has participated in any other investigational clinical study within 3 months of Screening (Part A only).
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method