Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43881   clinical trials with a EudraCT protocol, of which   7295   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2022-000317-14
    Sponsor's Protocol Code Number:RAD-GRIN-101
    National Competent Authority:Germany - BfArM
    Clinical Trial Type:EEA CTA
    Trial Status:Trial now transitioned
    Date on which this record was first entered in the EudraCT database:2022-08-30
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedGermany - BfArM
    A.2EudraCT number2022-000317-14
    A.3Full title of the trial
    A Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics, and Effect on Seizures and Behavioral Symptoms of Multiple Individually Titrated Doses of Radiprodil in Children with GRIN-related Disorder
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Study with Radiprodil in Children with GRIN-related Disorder
    A.4.1Sponsor's protocol code numberRAD-GRIN-101
    A.5.4Other Identifiers
    Name:IND NumberNumber:160112
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorGRIN Therapeutics, Inc.
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportGRIN Therapeutics, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationGRIN Therapeutics, Inc.
    B.5.2Functional name of contact pointClinical Operations
    B.5.3 Address:
    B.5.3.1Street Address101 Main Street, Suite 1210
    B.5.3.2Town/ cityCambridge Massachusetts
    B.5.3.3Post code02142
    B.5.3.4CountryUnited States
    B.5.6E-mailVijay.Rai@grintherapeutics.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameRadiprodil
    D.3.4Pharmaceutical form Granules and solvent for oral suspension
    D.3.4.1Specific paediatric formulation Yes
    D.3.7Routes of administration for this IMPEnteral use (Noncurrent)
    Oral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNRadiprodil
    D.3.9.1CAS number 496054-87-6
    D.3.9.2Current sponsor codeRadiprodil Form A
    D.3.9.4EV Substance CodeSUB187493
    D.3.10 Strength
    D.3.10.1Concentration unit % (W/W) percent weight/weight
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameRadiprodil
    D.3.4Pharmaceutical form Granules and solvent for oral suspension
    D.3.4.1Specific paediatric formulation Yes
    D.3.7Routes of administration for this IMPEnteral use (Noncurrent)
    Oral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNRadiprodil
    D.3.9.1CAS number 496054-87-6
    D.3.9.2Current sponsor codeRadiprodil Form A
    D.3.9.4EV Substance CodeSUB187493
    D.3.10 Strength
    D.3.10.1Concentration unit % (W/W) percent weight/weight
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    gain of function (GoF) variants in the GRIN 1, 2A, 2B or 2D genes
    E.1.1.1Medical condition in easily understood language
    GRIN-related disorder
    E.1.1.2Therapeutic area Diseases [C] - Nervous System Diseases [C10]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 26.0
    E.1.2Level PT
    E.1.2Classification code 10064062
    E.1.2Term Neurodevelopmental disorder
    E.1.2System Organ Class 10029205 - Nervous system disorders
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    •To determine the 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
    •To determine the pharmacokinetics (PK) and plasma exposure of radiprodil
    E.2.2Secondary objectives of the trial
    •To evaluate initial signs of efficacy on frequency and severity of epileptic seizures in those participants with seizures
    •To evaluate initial signs of efficacy of radiprodil on additional central nervous system (CNS) features including, behavior, motor symptoms, sleep, quality of life, and the maintenance of the treatment effect
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    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.
    E.4Principal 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 <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).
    E.5 End points
    E.5.1Primary end point(s)
    •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
    •Plasma concentrations of radiprodil at predefined timepoints
    E.5.1.1Timepoint(s) of evaluation of this end point
    Please refer to the Schedule of Events presented in the study protocol (Table 2-1 (Part A), page 17-18 and to Table 2-2 (Part B), page 21-22)
    E.5.2Secondary end point(s)
    •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 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]), and Clinical Global Impression of Change [CGI-C] scales)
    E.5.2.1Timepoint(s) of evaluation of this end point
    Please refer to the Schedule of Events presented in the study protocol (Table 2-1 (Part A), page 17-18 and to Table 2-2 (Part B), page 21-22)
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) Yes
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other Yes
    E.7.1.3.1Other trial type description
    Phase 1B study
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial1
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned2
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA9
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Canada
    Germany
    Italy
    Netherlands
    Spain
    United States
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months9
    E.8.9.1In the Member State concerned days15
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months9
    E.8.9.2In all countries concerned by the trial days15
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 Yes
    F.1.1Number of subjects for this age range: 24
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) Yes
    F.1.1.4.1Number of subjects for this age range: 4
    F.1.1.5Children (2-11years) Yes
    F.1.1.5.1Number of subjects for this age range: 20
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) No
    F.1.3Elderly (>=65 years) No
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    children with neurodevelopmental disorders
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state10
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 18
    F.4.2.2In the whole clinical trial 24
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    Standard of care
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2022-12-20
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2023-04-20
    P. End of Trial
    P.End of Trial StatusTrial now transitioned
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Sun May 19 10:21:51 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA