Astroscape: A Study of Radiprodil on Safety, Tolerability, Pharmacokinetics, and Effect on Seizures and Behavioral Symptoms in Patients With TSC or FCD Type II

NCT06392009 | Active Not Recruiting Phase 1 DMC

• 2 other identifiers: RAD-GRIN-2012023-506301-20-00
• Study Type: interventional
• Target: 30
• Locations: 8 countries
• Sites: 18

Brief Summary

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.

Conditions

Tuberous Sclerosis Complex; Focal Cortical Dysplasia

Keywords

TSC; FCD; Tuberous Sclerosis Complex; Focal Cortical Dysplasia; Astroscape

Outcome Measures

Primary Outcomes (16)

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 12-Lead ECG: Mean change from Baseline to End-of-Treatment in RR interval

  from Baseline to End-of-study: 1 year 6 months

• 12-Lead ECG: Mean change from Baseline to End-of-Treatment in PR interval

  from Baseline to End-of-study: 1 year 6 months

• 12-Lead ECG: Mean change from Baseline to End-of-Treatment in QRS interval

  from Baseline to End-of-study: 1 year 6 months

• 12-Lead ECG: Mean change from Baseline to End-of-Treatment in QT interval

  from Baseline to End-of-study: 1 year 6 months

• 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 Outcomes (9)

• Percent change from baseline in Video-EEG seizure burden

  Baseline to end-of-treatment: week 6 to week 76

• Change from baseline in seizure frequency

  Baseline to Maintenance Visit 7: week 6 to week 25 and Baseline to end-of-treatment: week 6 to week 76

• Change from baseline in number of seizure-free days and longest period with no seizures

  Baseline to end-of-treatment: week 6 to week 76

• Aberrant Behavior Checklist-Community (ABC-2C)

  Baseline to end-of-treatment: week 6 to week 76

• Caregiver Global Impression of Change (CaGI-C)

  Baseline to end-of-treatment: week 6 to week 76

Study Arms (2)

TSC

EXPERIMENTAL

Liquid suspension of radiprodil, at concentrations 0.25 mg/mL, 2.50 mg/mL or 7.5 mg/mL for 1%, 10% and 30% formulation respectively. It will be administered twice a day (bid) either orally or via gastric or nasogastric tube.

Drug: Radiprodil

FCD Type II

EXPERIMENTAL

Liquid suspension of radiprodil, at concentrations 0.25 mg/mL, 2.50 mg/mL or 7.5 mg/mL for 1%, 10% and 30% formulation respectively. It will be administered twice a day (bid) either orally or via gastric or nasogastric tube.

Drug: Radiprodil

Interventions

Radiprodil DRUG

Radiprodil is an orally active, negative allosteric modulator of the NR2B subunit of the NMDA receptor.

FCD Type II; TSC

Eligibility Criteria

• Age: 6 Months - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Failed to respond to at least 2 anti-seizure medications (ASMs) at appropriate dosages and duration
• Disease specific criteria:
• diagnosis of FCD Type II based on clinical symptoms and confirmed by a positive magnetic resonance imaging (MRI)
• 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 months of the planned date of first dose of study drug

You may not qualify if:

• 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 screening 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.
• body weight \<10kg for whom a gastric tube is the only possibility for radiprodil dosing.

Sponsors & Collaborators

• GRIN Therapeutics, Inc.: lead

Study Sites (18)

Queensland Children Hospital

South Brisbane, 4101, Australia

Location

University Hospitals Leuven, Pediatric Neurology

Leuven, 3000, Belgium

Location

Alberta Children's Hospital

Calgary, T3A 2X6, Canada

Location

The Hospital for Sick Children (Sick Kids)

Toronto, M5G 1X8, Canada

Location

IRCCS Istituto Giannina Gaslini

Genoa, Liguria, 16146, Italy

Location

AOU Meyer

Florence, Tuscany, 50139, Italy

Location

Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS)

Roma, 00165, Italy

Location

Universita Cattolica del Sacro Cuore - Policlinico Universitario "Agostino Gemelli"

Roma, 00168, Italy

Location

UMC Uthrecht - Wilhelmina Kinderziekenhuis

Utrecht, 3508, Netherlands

Location

Uniwersyteckie Centrum Kliniczne

Gdansk, 80952, Poland

Location

Centrum Medyczne Plejady

Krakow, 30363, Poland

Location

Uniwersytecki Szpital Kliniczny w Poznaniu

Poznan, 60356, Poland

Location

Instytut Pomnik - Centrum Zdrowia Dziecka

Warsaw, 04730, Poland

Location

Hospital Universitario Vall D´Hebrón

Barcelona, 08035, Spain

Location

Hospital Materno Infantil Sant Joan de Deu de Barcelona

Barcelona, 08950, Spain

Location

Hospital Universitario Vithas La Milagrosa

Madrid, 28010, Spain

Location

Hospital Ruber Internacional

Madrid, 28034, Spain

Location

University Hospitals Bristol and Weston NHS Foundation Trust Bristol Royal Hospital for Children

Bristol, BS2 8BJ, United Kingdom

Location

MeSH Terms

Conditions

Tuberous Sclerosis; Focal Cortical Dysplasia

Interventions

radiprodil

Condition Hierarchy (Ancestors)

Hamartoma; Neoplasms; Neoplasms, Multiple Primary; Neoplastic Syndromes, Hereditary; Malformations of Cortical Development, Group I; Malformations of Cortical Development; Nervous System Malformations; Nervous System Diseases; Neurocutaneous Syndromes; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2024
• First Posted: April 30, 2024
• Study Start: July 10, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2028
• Last Updated: April 1, 2026

Record last verified: 2026-03

Locations

IT (4); NL (1); BE (1); GB (1); AU (1); CA (2); PL (4); ES (4)