Tuberous Sclerosis Complex Clinical Trial
Official title:
A Multicenter, Open-label Study to Assess the Safety, Tolerability, Pharmacokinetics, and Effect on Seizures and Behavioral Symptoms of Radiprodil in Patients With Tuberous Sclerosis Complex (TSC) or Focal Cortical Dysplasia (FCD) Type II
Study RAD-GRIN-201 is a phase 1B/2A trial to assess safety, tolerability, pharmacokinetics (PK), and potential efficacy of radiprodil in participants with Tuberous Sclerosis Complex (TSC) or Focal Cortical Dysplasia (FCD) type II. The study is open-label, so all participants will be treated with radiprodil. Subjects' participation in the study is expected to last up to six months in Part A and one year in Part B/long-term treatment period. The treatment period in Part B may be extended based on a favorable benefit/risk profile.
Status | Recruiting |
Enrollment | 30 |
Est. completion date | July 2026 |
Est. primary completion date | July 2025 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 6 Months to 18 Years |
Eligibility | Inclusion Criteria: - Failed to respond to at least 2 anti-seizure medications (ASMs) at appropriate dosages and duration. - Disease specific criteria: 1. diagnosis of FCD Type II based on clinical symptoms and confirmed by a positive magnetic resonance imaging (MRI) 2. diagnosis of TSC by either clinical or genetic diagnostic criteria (Northrup, 2021) as documented in the participant's medical record. - Participant on average has had at least 8 countable/witnessed primary seizures during a 4-week baseline period with at least 1 seizure occurring in at least 3 of the 4 weeks of baseline - All medical interventions for epilepsy / behavior (including ketogenic diet and any neurostimulation devices) should be stable for 28 days prior to screening with no more than 6 days per month use of rescue medication. Participants must remain on a stable regimen throughout the treatment period. - Participant has had an MRI scan within 12 weeks of screening or during the screening period. Exclusion Criteria: - Any other clinically relevant medical, neurologic, or psychiatric condition and/or behavioral disorder unrelated to TSC or FCD Type II 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. - Clinically significant laboratory or ECG abnormalities. - Severe hepatic dysfunction (Child-Pugh grade C). - History of brain surgery within 6 months of enrollment for epilepsy or any other reason. - Contraindications to radiprodil or with known hypersensitivity to the active substance or the excipients or other chemically closely related substances. - Receiving treatment with contraindicated concomitant drugs such as agonists or antagonists of the glutamate receptor, including but not limited to felbamate, memantine, and perampanel. |
Country | Name | City | State |
---|---|---|---|
Australia | Queensland Children Hospital | South Brisbane | Queensland |
Belgium | Universitair Ziekenhuis Antwerpen (UZA) | Antwerp | |
Belgium | University Hospitals Leuven, Pediatric Neurology | Leuven | |
Canada | Alberta Children's Hospital | Calgary | Alberta |
Canada | The Hospital for Sick Children (Sick Kids) | Toronto | |
Canada | BC Children's Hospital | Vancouver | |
Italy | AOU Meyer | Florence | Toscana |
Italy | IRCCS Istituto Giannina Gaslini | Genoa | Liguria |
Italy | Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) | Roma | |
Italy | Universita Cattolica del Sacro Cuore - Policlinico Universitario "Agostino Gemelli" | Roma | |
Poland | Uniwersyteckie Centrum Kliniczne | Gdansk | |
Poland | Centrum Medyczne Plejady | Kraków | |
Poland | Uniwersytecki Szpital Kliniczny w Poznaniu | Poznan | |
Poland | Instytut Pomnik - Centrum Zdrowia Dziecka | Warszawa | |
Spain | Hospital Materno Infantil Sant Joan de Deu de Barcelona | Barcelona | |
Spain | Hospital Universitario Vall D´Hebrón | Barcelona | |
Spain | Hospital Ruber Internacional | Madrid | |
Spain | Hospital Universitario Vithas La Milagrosa | Madrid | |
United Kingdom | University Hospitals Bristol and Weston NHS Foundation Trust Bristol Royal Hospital for Children | Bristol | |
United Kingdom | Royal Hospital for Children | Glasgow |
Lead Sponsor | Collaborator |
---|---|
GRIN Therapeutics, Inc. |
Australia, Belgium, Canada, Italy, Poland, Spain, United Kingdom,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Incidence of Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (SAEs), Adverse Drug Reactions (ADRs), TEAEs Leading to Discontinuation and Severity of TEAEs | Frequency, type, severity and duration of adverse events, serious adverse events and adverse drug reactions. | from Baseline to End-of-study: 1 year 6 months | |
Primary | Plasma concentration of radiprodil and maximum plasma concentration (Cmax) | Titration Visit 1 (week 7): Pre-dose to 12 hours post-dose. Titration Visits 2,3,4 (week 8 to 13) and Maintenance Visit 7 (week 25): pre-dose to 5 hours post-dose | ||
Primary | Plasma concentration of radiprodil versus time, area under the curve (AUCt) | Titration Visit 1 (week 7): Pre-dose to 12 hours post-dose. Titration Visits 2,3,4 (week 8 to 13) and Maintenance Visit 7 (week 25): pre-dose to 5 hours post-dose | ||
Primary | Pharmacokinetic plasma concentration of radiprodil: half-life (T1/2) | Titration Visit 1 (week 7): Pre-dose to 12 hours post-dose. Titration Visits 2,3,4 (week 8 to 13) and Maintenance Visit 7 (week 25): pre-dose to 5 hours post-dose | ||
Primary | Pharmacokinetic plasma concentration of radiprodil: time to Cmax (Tmax) | Titration Visit 1 (week 7): Pre-dose to 12 hours post-dose. Titration Visits 2,3,4 (week 8 to 13) and Maintenance Visit 7 (week 25): pre-dose to 5 hours post-dose | ||
Primary | Pharmacokinetic plasma concentration of radiprodil, clearance (Cl) | Titration Visit 1 (week 7): Pre-dose to 12 hours post-dose. Titration Visits 2,3,4 (week 8 to 13) and Maintenance Visit 7 (week 25): pre-dose to 5 hours post-dose | ||
Primary | Number of participants with abnormal laboratory tests results | The clinical laboratory tests include Hematology, Serum Chemistry and Coagulation | from Baseline to End-of-study: 1 year 6 months | |
Primary | Number of participants with abnormal physical and neurological examination findings | A complete physical and neurological examination according to standard of care excluding the genitourinary examination will be performed | Baseline, MV7, and in Part B: Month 3, 6, 9, 12: week 6, week 28, week 40, week 52, week 64, week 76 | |
Primary | Clinically relevant changes in safety parameters: systolic blood pressure | changes from Baseline to End of study for systolic blood pressure | from Baseline to End-of-study: 1 year 6 months | |
Primary | Clinically relevant changes in safety parameters: diastolic blood pressure | changes from Baseline to End of study for diastolic blood pressure | from Baseline to End-of-study: 1 year 6 months | |
Primary | Clinically relevant changes in safety parameters: pulse rate | changes from Baseline to End of Treatment for pulse rate | from Baseline to End-of-study: 1 year 6 months | |
Primary | 12-Lead ECG: Mean change from Baseline to End-of-Treatment in RR interval | from Baseline to End-of-study: 1 year 6 months | ||
Primary | 12-Lead ECG: Mean change from Baseline to End-of-Treatment in PR interval | from Baseline to End-of-study: 1 year 6 months | ||
Primary | 12-Lead ECG: Mean change from Baseline to End-of-Treatment in QRS interval | from Baseline to End-of-study: 1 year 6 months | ||
Primary | 12-Lead ECG: Mean change from Baseline to End-of-Treatment in QT interval | from Baseline to End-of-study: 1 year 6 months | ||
Primary | 12-Lead ECG: Mean change from Baseline to End-of-Treatment in QTcF interval | from Baseline to End-of-study: 1 year 6 months | ||
Secondary | Percent change from baseline in Video-EEG seizure burden | Assessed by 8- to 24- hour video electroencephalogram | Baseline to end-of-treatment: week 6 to week 76 | |
Secondary | Change from baseline in seizure frequency | assessed by seizure diaries | Baseline to Maintenance Visit 7: week 6 to week 25 and Baseline to end-of-treatment: week 6 to week 76 | |
Secondary | Change from baseline in number of seizure-free days and longest period with no seizures | assessed by seizure diaries | Baseline to end-of-treatment: week 6 to week 76 | |
Secondary | Aberrant Behavior Checklist-Community (ABC-2C) | The ABC-2C is a standardized 58-item caregiver-reported problem-behavior rating scale, originally designed to assess treatment effects in people with intellectual disabilities. Each item is scored from 0 (never a problem) to 3 (severe problem). Items load onto one of five empirically derived subscales: Irritability, Agitation, & Crying (15 items); Lethargy/Social Withdrawal (16 items); Stereotypic Behavior (7 items); Hyperactivity/Noncompliance (16 items); and Inappropriate Speech (4 items). A total score would range from 0 to 174. | Baseline to end-of-treatment: week 6 to week 76 | |
Secondary | Caregiver Global Impression of Change (CaGI-C) | The CaGI-C is a 7-point caregiver-rated scale ranging from 1 (very much improved) to 7 (very much worse). | Baseline to end-of-treatment: week 6 to week 76 | |
Secondary | Clinical Global Impression of Change [CGI-C] | The CGI scale is a clinician-rated measures of change of a symptom or condition, using a single item, 6- or 7-point scale. The CGI-C scale ranges from 1 ("Very much worse") to 7 ("Very much improved"). | Baseline to end-of-treatment: week 6 to week 76 | |
Secondary | Pediatric Quality of Life Inventory [PedsQL] | The PedsQL is a 23-item generic health status instrument assessing 5 domains of health in children. It's a 0-100 scale, and higher scores are indicative of better health-related quality of life. | Baseline to end-of-treatment: week 6 to week 76 | |
Secondary | Caregiver Burden Inventory (CBI) | The CBI is a validated scale providing information regarding the impact of caregiving on the lives of caregivers. It comprises 24 closed questions divided into 5 dimensions. Each dimension includes 4 or 5 items. Each item is given a score between 0 and 4, where higher scores indicate greater caregiver burden. | Baseline to end-of-treatment: week 6 to week 76 | |
Secondary | Columbia-Suicide Severity Rating Scale (C-SSRS) | The C-SSRS is a validated tool designed to systematically evaluate the severity and intensity of suicidal ideation and behavior. The scoring system ranges from 0 to 5 for suicidal ideation and from 0 to 25 for suicidal behavior, with higher scores indicating greater severity or greater frequency of suicidal thoughts or actions. | Baseline to end-of-treatment: week 6 to week 76 |
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