Authorised Therapeutic confirmatory (Phase III) GRIN-related neurodevelopmental disorder

A Multinational, Multicenter Study With an Open-Label Phase 1b and a Randomized, Double-Blind, Placebo-Controlled Phase 3 Followed by an Open-Label Extension to Assess the Efficacy, Safety, Tolerability, and Pharmacokinetics of Radiprodil in Participants With GRIN-Related Neurodevelopmental Disorder

EU CTIS ID: 2023-509672-42-00

What this study is testing

PART A - PHASE 1b To determine the long-term safety and tolerability of multiple individually titrated doses of radiprodil as an add-on therapy to standard of care (SOC) in pediatric participants To establish a safe and well tolerated dose after 8 weeks of continuous treatment in Part A To determine the pharmacokinetics (PK) and plasma exposure of radiprodil PART A – PHASE 3 RANDOMIZED QUALIFYING SEIZURES COHORT To evaluate the change in seizure frequency following treatment with radiprodil compared with placebo PART A – PHASE 3 RANDOMIZED WITHOUT QUALIFYING SEIZURES AUXILIARY COHORT To evaluate the efficacy of radiprodil compared with placebo on non-seizure behavior features PART B – OLE STUDY To determine the long-term safety and tolerability of radiprodil

  • Therapeutic confirmatory (Phase III)

A plain-language read of the study's public EU CTIS listing. The study team confirms the details.

Who can take part

You may be able to join if

  • 1. PART A AND PART B - PHASE 1b : 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.
  • 10. PART A – PHASE 3 RANDOMIZED QUALIFYING SEIZURES COHORT: 2. Participant experiences the following: a. At least 1 CMS (defined here) per week and ≥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.
  • 11. PART A – PHASE 3 RANDOMIZED QUALIFYING SEIZURES COHORT: 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.
  • 12. PART A – PHASE 3 RANDOMIZED QUALIFYING SEIZURES COHORT: 4. Participant has signed informed consent or participant’s caregivers have signed informed consent and participant has signed assent (if applicable).
  • 13. PART A – PHASE 3 RANDOMIZED QUALIFYING SEIZURES COHORT: 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.
  • 14. PART A – PHASE 3 RANDOMIZED QUALIFYING SEIZURES COHORT: 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.

You likely can't join if

  • 1. PART A AND B – PHASE 1b: 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.
  • 10. PART A – PHASE 3 RANDOMIZED COHORTS: 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.
  • 11. PART A – PHASE 3 RANDOMIZED COHORTS: 2. Participant or caregiver is unwilling or unable to comply with all procedures for the duration of study.
  • 12. PART A – PHASE 3 RANDOMIZED COHORTS: 3. Participant receiving >4 standard ASMs at the time of Screening.
  • 13. PART A – PHASE 3 RANDOMIZED COHORTS: 4. Participant with a body weight <5 kg at Screening.
  • 14. PART A – PHASE 3 RANDOMIZED COHORTS: 5. Participant with any clinically significant laboratory or ECG abnormalities according to the judgment of the investigator or the sponsor.
See the full eligibility criteria
Who can join
  • 1. PART A AND PART B - PHASE 1b : 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.
  • 10. PART A – PHASE 3 RANDOMIZED QUALIFYING SEIZURES COHORT: 2. Participant experiences the following: a. At least 1 CMS (defined here) per week and ≥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.
  • 11. PART A – PHASE 3 RANDOMIZED QUALIFYING SEIZURES COHORT: 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.
  • 12. PART A – PHASE 3 RANDOMIZED QUALIFYING SEIZURES COHORT: 4. Participant has signed informed consent or participant’s caregivers have signed informed consent and participant has signed assent (if applicable).
  • 13. PART A – PHASE 3 RANDOMIZED QUALIFYING SEIZURES COHORT: 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.
  • 14. PART A – PHASE 3 RANDOMIZED QUALIFYING SEIZURES COHORT: 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.
  • 15. PART A – PHASE 3 RANDOMIZED QUALIFYING SEIZURES COHORT: 7. Participant is willing to abstain from sperm or egg donation from Screening through 90 days after the last dose of study drug.
  • 16. PART A – PHASE 3 RANDOMIZED WITHOUT QUALIFYING SEIZURES AUXILIARY COHORT: 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).
  • 17. PART B OLE – PHASE 3 RANDOMIZED COHORTS: 1. 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 Part A.
  • 18. PART B OLE – PHASE 3 RANDOMIZED COHORTS: 2. 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 pregnancy test results at the TT1 Visit), nonlactating, and practicing one of the following medically acceptable methods of birth control throughout Part B 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 throughout Part B and for 90 days after the last dose of study drug.
  • 19. PART B OLE – PHASE 3 RANDOMIZED COHORTS: 3. Participant is willing to abstain from sperm or egg donation throughout Part B and for 90 days after the last dose of study drug.
  • 2. PART A AND PART B - PHASE 1b: 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).
  • 20. PART B OLE – PHASE 3 RANDOMIZED COHORTS: 4. Participant has completed Part A (remained on study and were compliant with dosing and study procedures [based on investigator and sponsor assessment] through the last visit of Part A) of the Phase 3 portion of the study. The participant is eligible to continue study participation according to the judgment of the investigator.
  • 3. PART A AND PART B - PHASE 1b: 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. PART A AND PART B - PHASE 1b: 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. PART A AND PART B - PHASE 1b: 5. Participant’s caregivers have signed informed consent and participant has signed assent (if applicable).
  • 6. PART A AND PART B - PHASE 1b: 6. Participant’s caregivers are willing and able to complete entries in the eDiary on a daily basis.
  • 7. PART A AND PART B - PHASE 1b: 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 (ie, condom) throughout the study period.
  • 8. PART A AND PART B - PHASE 1b: 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.
  • 9. PART A – PHASE 3 RANDOMIZED QUALIFYING SEIZURES COHORT: 1. Participants aged ≥1 month to ≤18 years with GRIN-NDD with GRIN1, GRIN2A, GRIN2B, or GRIN2D gene variants known to result in GoF of the NMDA receptor as determined using a functional characterization method consistent with Myers et al., 2023.
What rules you out
  • 1. PART A AND B – PHASE 1b: 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.
  • 10. PART A – PHASE 3 RANDOMIZED COHORTS: 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.
  • 11. PART A – PHASE 3 RANDOMIZED COHORTS: 2. Participant or caregiver is unwilling or unable to comply with all procedures for the duration of study.
  • 12. PART A – PHASE 3 RANDOMIZED COHORTS: 3. Participant receiving >4 standard ASMs at the time of Screening.
  • 13. PART A – PHASE 3 RANDOMIZED COHORTS: 4. Participant with a body weight <5 kg at Screening.
  • 14. PART A – PHASE 3 RANDOMIZED COHORTS: 5. Participant with any clinically significant laboratory or ECG abnormalities according to the judgment of the investigator or the sponsor.
  • 15. PART A – PHASE 3 RANDOMIZED COHORTS: 6. Participant has severe hepatic dysfunction (Child-Pugh grade C).
  • 16. PART A – PHASE 3 RANDOMIZED COHORTS: 7. Participant has a history of brain surgery within 6 months of randomization for epilepsy or any other reason.
  • 17. PART A – PHASE 3 RANDOMIZED COHORTS: 8. Participant with any known hypersensitivity to radiprodil drug product (DP) active substance or the excipients or other chemically closely related substances.
  • 18. PART A – PHASE 3 RANDOMIZED COHORTS: 9. Participant receiving treatment with prohibited concomitant drugs such as agonists or antagonists of the glutamate receptor, including but not limited to felbamate, memantine, and perampanel. If the participant has been on any of these listed drugs, they must have discontinued the drug at least 5 half-lives or 28 days prior to the planned first dose of study drug, whichever is longer.
  • 19. PART A – PHASE 3 RANDOMIZED COHORTS: 11. Participant has received any prior gene therapy.
  • 2. PART A AND B – PHASE 1b: 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).
  • 20. PART A – PHASE 3 RANDOMIZED COHORTS: 12. Participant is on treatment with hormonal therapy such as adrenocorticotrophic hormone or prednisolone.
  • 21. PART A – PHASE 3 RANDOMIZED COHORTS: 13. Participant has participated in any other investigational clinical study using an IP or device within 3 months or 5 half-lives of the IP, whichever is longer, of Screening.
  • 22. PART A – PHASE 3 RANDOMIZED COHORTS: 14. Participant has previously received radiprodil.
  • 23. PART B OLE – PHASE 3 RANDOMIZED COHORTS: 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.
  • 24. PART B OLE – PHASE 3 RANDOMIZED COHORTS: 2. Participant or caregiver is unwilling or unable to comply with all study procedures for the duration of the study.
  • 25. PART B OLE – PHASE 3 RANDOMIZED COHORTS: 3. Participant receiving >4 standard ASMs.
  • 26. PART B OLE – PHASE 3 RANDOMIZED COHORTS: 4. Participant with a body weight <5 kg.
  • 27. PART B OLE – PHASE 3 RANDOMIZED COHORTS: 5. Participant with any clinically significant laboratory or ECG abnormalities according to the judgment of the investigator or the sponsor.
  • 28. PART B OLE – PHASE 3 RANDOMIZED COHORTS: 6. Participant has severe hepatic dysfunction (Child-Pugh grade C).
  • 29. PART B OLE – PHASE 3 RANDOMIZED COHORTS: 7. Participant with any known hypersensitivity to radiprodil DP active substance or the excipients or other chemically closely related substances.
  • 3. PART A AND B – PHASE 1b: 3. Participant with any clinically significant laboratory or ECG abnormalities.
  • 30. PART B OLE – PHASE 3 RANDOMIZED COHORTS: 8. Participant receiving treatment with prohibited concomitant drugs such as agonists or antagonists of the glutamate receptor, including but not limited to felbamate, memantine, and perampanel.
  • 31. PART B OLE – PHASE 3 RANDOMIZED COHORTS: 9. Participant is on treatment with hormonal therapy such as adrenocorticotrophic hormone or prednisolone.
  • 4. PART A AND B – PHASE 1b: 4. Participant has severe hepatic dysfunction (Child-Pugh grade C).
  • 5. PART A AND B – PHASE 1b: 5. Participant has a history of brain surgery for epilepsy or any other reason.
  • 6. PART A AND B – PHASE 1b: 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. PART A AND B – PHASE 1b: 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. PART A AND B – PHASE 1b: 8. Participant is on treatment with hormonal therapy such as adrenocorticotrophic hormone or prednisolone (Part A only).
  • 9. PART A AND B – PHASE 1b: 9. Participant has participated in any other investigational clinical study within 3 months of Screening (Part A only).

The study team makes the final eligibility decision.

Where it's taking place

  • Australia
  • Canada
  • Japan
  • United States
  • Korea, Republic of
  • Singapore
  • Taiwan
  • United Kingdom

Questions & answers

Do participants get paid in this trial?

This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.

Is it free to join, and do I need insurance?

Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.

How long does this study last?

The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.

Who can join this trial?

This study is enrolling all sexes, 0-17 years, 18-64 years. The study team makes the final eligibility decision.

Where is this trial taking place?

Study sites include Australia; Canada; Japan; United States; Korea, Republic of; Singapore and 2 more location(s). Enter your location above to see the nearest site and check your eligibility.

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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.