GRIN-Related Neurodevelopmental Disorder
Conditions
Interventions
PART A - PHASE 3 RANDOMIZED QUALIFYING SEIZURES COHORT: Based on a dose escalation regimen design, dosing will begin at 0.125 mg/kg of Radiprodil and will be sequentially increased to 0.25 mg/kg and 0
Sponsors
Chin Russell
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: PART A - PHASE 3 RANDOMIZED QUALIFYING SEIZURES COHORT: A participant will be eligible for study participation in Part A for the Randomized Qualifying Seizures Cohort of the Phase 3 portion of the study if they meet all of the following inclusion criteria. Note: Participants can be rescreened only once in exceptional cases at the discretion of the investigator and with approval from the medical monitor. 1. Participants aged >=1 month to =4 CMS (generalized or focal) during the prospective 4-week Observation Period immediately preceding randomization. b. Has not obtained adequate response to at least 2 standard ASMs used at appropriate dose and duration with assured medication adherence (if applicable). Participant will continue to receive SOC ASMs while receiving study drug. 3. Participants must be on a stable dose of standard ASMs regardless of indication for at least 4 weeks prior to and during the Screening Period and should remain on stable doses throughout the study. Nonpharmacological treatments such as ketogenic diet should also be kept stable during screening and participation in the study. 4. Participant has signed informed consent or participant's caregivers have signed informed consent and participant has signed assent (if applicable). 5. Participant's caregivers are willing and able to complete entries in the eDiary on a daily basis and have demonstrated compliance (based on investigator and sponsor review) with eDiary entries during the Screening Period. 6. Participant is one 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 one of the following medically acceptable methods of birth control from Screening through 90 days after the last dose of study drug: -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 study drug administration. -Intrauterine device. c. If male, is willing to use a condom from Screening through 90 days after the last dose of study drug. 7. Participant is willing to abstain from sperm or egg donation from Screening through 90 days after the last dose of study drug. PART A (PHASE 3 RANDOMIZED WITHOUT QUALIFYING SEIZURES AUXILIARY COHORT): A participant will be eligible for study participation in Part A for the Randomized Without Qualifying Seizures Auxiliary Cohort of the Phase 3 portion of the study if they meet all of the following inclusion criteria: 1. Participant experiences significant neurodevelopmental symptoms based on caregiver report with a GRIN-CGI-S score >=4 at the Screening Visit and Day 1 of Visit T1. For all other inclusion criteria, see Inclusion Criteria for Part A - Phase 3 Randomized Qualifying Seizures Cohort with the exception of inclusion criterion 2 (eg, participants with seizures that are not CMS or those with <1 CMS per week would be eligible for the Randomized Without Qualifying Seizures Auxiliary Cohort). PART B O
Exclusion criteria
Exclusion criteria: PART A - PHASE 3 RANDOMIZED QUALIFYING SEIZURES COHORT: A participant will be excluded from the Phase 3 portion of the study if they meet any of the following criteria: 1. Participant with any other clinically relevant medical, neurologic, or psychiatric condition and/or behavioral disorder (including those related to GRIN-NDD) that would preclude or jeopardize the participant's safe participation or administration of study drug or the conduct of the study according to the judgment of the investigator or the sponsor. 2. Participant or caregiver is unwilling or unable to comply with all procedures for the duration of study. 3. Participant receiving >4 standard ASMs at the time of Screening. 4. Participant with a body weight 4 standard ASMs. 4. Participant with a body weight <5 kg. 5. Participant with any clinically significant laboratory or ECG abnormalities according to the judgment of the investigator or the sponsor. 6. Participant has severe hepatic dysfunction (Child-Pugh grade C). 7. Participant with any known hypersensitivity to radiprodil DP active substance or the excipients or other chemically closely related substances. 8. Particip
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| PART A - PHASE 3 RANDOMIZED QUALIFYING SEIZURES COHORT:Countable motor seizure (CMS; defined here) frequency (per 28 days) during the Maintenance Period (Weeks 1 through 12), as captured in the daily seizure eDiary PART A - PHASE 3 RANDOMIZED WITHOUT QUALIFYING SEIZURES AUXILIARY COHORT:AEs, SAEs, and ADRs (frequency, type, severity, and duration) PART B OLE - PHASE 3 RANDOMIZED COHORTS: AEs, SAEs, and ADRs (frequency, type, severity, and duration) | — |
Secondary
| Measure | Time frame |
|---|---|
| PART A - PHASE 3 RANDOMIZED QUALIFYING SEIZURES COHORT: - Proportion of participants with >=50% reduction in CMS frequency (per 28 days) from baseline (the last 4 weeks prior to randomization) to the entire Maintenance Period (Weeks 1 through 12), as captured in the daily seizure eDiary - Change in the number of CMS-free days (per 28 days) from baseline (the last 4 weeks prior to randomization) to the entire Maintenance Period (Weeks 1 through 12), as captured in the daily seizure eDiary - Cumulative distribution of percent reduction in seizure frequency from Baseline to the entire Maintenance Period (Weeks 1 through 12) - GRIN-NDD-specific CGI-C (GRIN-CGI-C) evaluated at the end of the Maintenance Period (Week 12) relative to baseline for relevant domains, including expressive communication, receptive communication, fine motor, gross motor, and dysregulated behavior - Change from baseline to the end of the Maintenance Period (Week 12) in the ABC-2C irritability subscale score - Change from baseline to the end of the Maintenance Period (Week 12) in the Vineland Adaptive Behavior Scale, Third Edition (VABS-3) Daily Living personal subdomain score PART A - PHASE 3 RANDOMIZED WITHOUT QUALIFYING SEIZURES AUXILIARY COHORT: - GRIN-CGI-C evaluated at the end of the Maintenance Period (Week 24) relative to baseline for relevant domains, including expressive communication, receptive communication, fine motor, gross motor, and dysregulated behavior - Change from baseline to the end of the Maintenance Period (Week 24) in the ABC-2C irritability subscale score - Change from baseline to the end of the Maintenance Period (Week 24) in the VABS-3 Daily Living personal subdomain score PART B OLE - PHASE 3 RANDOMIZED COHORTS: - Percent change in the CMS frequency per 28 days from baseline to each 12-week interval in the open-label extension (OLE) through the end of the OLE, as captured in the daily seizure eDiary - Change in the number of CMS-free days per 28 days from baseline to | — |
Countries
Australia, Belgium, Canada, France, Germany, Italy, Japan, Korea, Netherlands, Poland, Singapore, Slovenia, Spain, Taiwan, UK, US
Contacts
Public Contactintellim inquiry desk for JRCT
intellim Corporation
Outcome results
None listed