Trial Title:
Astroscape: A Study of Radiprodil on Safety, Tolerability, Pharmacokinetics, and Effect on Seizures and Behavioral Symptoms in Patients With TSC or FCD Type II
NCT ID:
NCT06392009
Condition:
Tuberous Sclerosis Complex
Focal Cortical Dysplasia
Conditions: Official terms:
Tuberous Sclerosis
Seizures
Malformations of Cortical Development
Focal Cortical Dysplasia
Sclerosis
Behavioral Symptoms
Conditions: Keywords:
TSC
FCD
Tuberous Sclerosis Complex
Focal Cortical Dysplasia
Astroscape
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Radiprodil
Description:
Radiprodil is an orally active, negative allosteric modulator of the NR2B subunit of the
NMDA receptor.
Arm group label:
FCD Type II
Arm group label:
TSC
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.
Detailed description:
Approximately 20 participants with TSC and 10 participants with FCD type II will be
enrolled.
The effects of radiprodil are assessed in participants with treatment-resistant seizures
(with or without behavioral symptoms). The daily doses of radiprodil will be individually
titrated for every participant and all the participants will receive study drug.
This study is divided into the following periods:
PART A:
- Screening/Observation Period (up to six(6) weeks): Investigators assess eligibility
followed by an Observation Period (at least four(4) weeks) to evaluate seizure
frequency.
- Titration Period (approx. four(4) weeks): Radiprodil twice daily will be
administered in escalating doses and plasma concentrations, safety, and tolerability
assessed. Once a safe and potentially effective dose has been established, the
participant will immediately enter the Maintenance Period.
- Maintenance Period (approx. twelve(12) weeks): The participant will continue to take
the safe and potentially effective dose identified during the Titration Period. At
the end of the Maintenance Period the participant will either be invited to enter
Part B or the Tapering and Safety Follow-up Period.
- Tapering (15 days) and Safety Follow-up Period (14 days): a participant who doesn't
take part in the long-term treatment period (Part B) will taper (ie gradually
decrease) the study medicine for 15 days and enter a safety Follow-up Period (14
days). In this case, the participant will have one (1) last visit at the end of the
safety Follow-up Period.
PART B:
- Long-Term Treatment Period (one(1) year): During the Long-Term Treatment Period
(Part B), participants will continue taking radiprodil at the usual dose level and
making regular visits to the study site.
- Tapering (15 days) and Safety Follow-up Period (14 days): at the end of the
long-term treatment period (Part B), the participant will taper (ie gradually
decrease) the study medicine for 15 days and enter a safety Follow-up Period (14
days) after his/her last dose of radiprodil. The participant will have one (1) last
visit at the end of the safety Follow-up Period.
Criteria for eligibility:
Criteria:
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.
Gender:
All
Minimum age:
6 Months
Maximum age:
18 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Queensland Children Hospital
Address:
City:
South Brisbane
Zip:
4101
Country:
Australia
Status:
Not yet recruiting
Investigator:
Last name:
Catherine Riney
Email:
Principal Investigator
Facility:
Name:
Universitair Ziekenhuis Antwerpen (UZA)
Address:
City:
Antwerp
Zip:
2650
Country:
Belgium
Status:
Not yet recruiting
Investigator:
Last name:
Anna Jansen
Email:
Principal Investigator
Facility:
Name:
University Hospitals Leuven, Pediatric Neurology
Address:
City:
Leuven
Zip:
3000
Country:
Belgium
Status:
Not yet recruiting
Investigator:
Last name:
Katherine Jansen
Email:
Principal Investigator
Facility:
Name:
Alberta Children's Hospital
Address:
City:
Calgary
Zip:
T3A 2X6
Country:
Canada
Status:
Not yet recruiting
Investigator:
Last name:
Julia Jacobs-Levan
Email:
Principal Investigator
Facility:
Name:
The Hospital for Sick Children (Sick Kids)
Address:
City:
Toronto
Zip:
M5G 1X8
Country:
Canada
Status:
Not yet recruiting
Investigator:
Last name:
Puneet Jain
Email:
Principal Investigator
Facility:
Name:
BC Children's Hospital
Address:
City:
Vancouver
Zip:
BC V6H 3N1
Country:
Canada
Status:
Not yet recruiting
Investigator:
Last name:
Mary Connolly
Email:
Principal Investigator
Facility:
Name:
IRCCS Istituto Giannina Gaslini
Address:
City:
Genoa
Zip:
16146
Country:
Italy
Status:
Recruiting
Investigator:
Last name:
Maria Cristina Diana
Email:
Principal Investigator
Facility:
Name:
AOU Meyer
Address:
City:
Florence
Zip:
50139
Country:
Italy
Status:
Recruiting
Investigator:
Last name:
Renzo Guerrini
Email:
Principal Investigator
Facility:
Name:
Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS)
Address:
City:
Roma
Zip:
00165
Country:
Italy
Status:
Recruiting
Investigator:
Last name:
Nicola Specchio
Email:
Principal Investigator
Facility:
Name:
Universita Cattolica del Sacro Cuore - Policlinico Universitario "Agostino Gemelli"
Address:
City:
Roma
Zip:
00168
Country:
Italy
Status:
Recruiting
Investigator:
Last name:
Domenica Battaglia
Email:
Principal Investigator
Facility:
Name:
UMC Uthrecht - Wilhelmina Kinderziekenhuis
Address:
City:
Utrecht
Zip:
3508
Country:
Netherlands
Status:
Not yet recruiting
Investigator:
Last name:
Floor Jansen
Email:
Principal Investigator
Facility:
Name:
Uniwersyteckie Centrum Kliniczne
Address:
City:
Gdańsk
Zip:
80952
Country:
Poland
Status:
Not yet recruiting
Investigator:
Last name:
Maria Mazurkiewicz-Beldzinska
Email:
Principal Investigator
Facility:
Name:
Centrum Medyczne Plejady
Address:
City:
Kraków
Zip:
30363
Country:
Poland
Status:
Recruiting
Investigator:
Last name:
Marta Zolnowska
Email:
Principal Investigator
Facility:
Name:
Uniwersytecki Szpital Kliniczny w Poznaniu
Address:
City:
Poznan
Zip:
60356
Country:
Poland
Status:
Not yet recruiting
Investigator:
Last name:
Barbara Steinborn
Email:
Principal Investigator
Facility:
Name:
Instytut Pomnik - Centrum Zdrowia Dziecka
Address:
City:
Warszawa
Zip:
04730
Country:
Poland
Status:
Recruiting
Investigator:
Last name:
Sergiusz Jozwiak
Email:
Principal Investigator
Facility:
Name:
Hospital Universitario Vall D´Hebrón
Address:
City:
Barcelona
Zip:
08035
Country:
Spain
Status:
Recruiting
Investigator:
Last name:
Manuel Toledo Argani
Email:
Principal Investigator
Facility:
Name:
Hospital Materno Infantil Sant Joan de Deu de Barcelona
Address:
City:
Barcelona
Zip:
08950
Country:
Spain
Status:
Recruiting
Investigator:
Last name:
Federico Ramos
Email:
Principal Investigator
Facility:
Name:
Hospital Universitario Vithas La Milagrosa
Address:
City:
Madrid
Zip:
28010
Country:
Spain
Status:
Recruiting
Investigator:
Last name:
Angel Aledo-Serrano
Email:
Principal Investigator
Facility:
Name:
Hospital Ruber Internacional
Address:
City:
Madrid
Zip:
28034
Country:
Spain
Status:
Recruiting
Investigator:
Last name:
Antonio Gil-Nagel
Email:
Principal Investigator
Facility:
Name:
University Hospitals Bristol and Weston NHS Foundation Trust Bristol Royal Hospital for Children
Address:
City:
Bristol
Zip:
BS2 8BJ
Country:
United Kingdom
Status:
Not yet recruiting
Investigator:
Last name:
Sam Amin
Email:
Principal Investigator
Start date:
July 10, 2024
Completion date:
July 2026
Lead sponsor:
Agency:
GRIN Therapeutics, Inc.
Agency class:
Industry
Source:
GRIN Therapeutics, Inc.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06392009
