RADIPRODIL for Tuberous sclerosis complex | Focal cortical dysplasia Type II

Inclusion criteria

• {"criterion_text":"- Age range: ≥ 6 months up to 18 years at Part A Baseline\n- Failed to respond to at least 2 anti-seizure medications (ASMs) at appropriate dosages and durations\n- Disease specific criteria: a. diagnosis of FCD Type II based on clinical symptoms and confirmed by a positive magnetic resonance imaging (MRI) b. diagnosis of TSC by either clinical or genetic diagnostic criteria (Northrup, 2021) as documented in the participant’s medical record.\n- Participant on average has had at least 8 countable motor seizures during a 4 week baseline period with at least 1 seizure occurring in at least 3 of the 4 weeks of Baseline\n- 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 should remain on a stable regimen throughout the treatment period.\n- Participant’s or their caregivers have signed informed consent and participant has signed assent (if applicable).\n- Participant’s or their caregivers are willing and able to complete entries in the eDiary on a daily basis.\n- Participant has had an MRI scan within 12 months of the planned date of first dose of study drug.\n- 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 (see Section 11.3.4), is nonpregnant (negative serum pregnancy test results at Screening and negative urine pregnancy test results at Baseline), nonlactating, and practicing 1 of the following medically acceptable methods of birth control from Screening through 90 days after the last dose of study drug: • Abstinence 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 condom from Screening through 90 days after the last dose of study drug."}

Exclusion criteria

• {"criterion_text":"- Participant with 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.\n- Participant with any clinically significant laboratory or ECG abnormalities that according to the Investigator in consultation with the Sponsor would jeopardize the safety of the participant, limit participation, or compromise the interpretation of the safety data from the participant.\n- Participant has severe hepatic dysfunction (Child-Pugh grade C).\n- Participant has a history of brain surgery within 6 months of Screening for epilepsy or any other reason.\n- Participant with any contraindications to radiprodil or with known hypersensitivity to the active substance or the excipients or other chemically closely related substances.\n- Participant receiving treatment with contraindicated concomitant drugs such as agonists or antagonists of the glutamate receptor, including but not limited to felbamate, memantine, and perampanel.\n- Participant has received an investigational treatment within 3 months or 5 half-lives of Screening, whichever is longer."}

Primary endpoints

• {"endpoint_text":"- Adverse events (AEs), serious adverse events (SAEs), and adverse drug reactions (ADRs) (frequency, type, severity, and duration) over the course of treatment (Part A and Part B)  Changes in vital signs  Physical examination findings  12-lead electrocardiogram (ECG) findings  Clinically significant changes in laboratory parameters  Occurrence of suicidal ideation or behavior Plasma concentrations of radiprodil at predefined timepoints","definition_or_measurement_approach":"Safety endpoints measured by recording AEs/SAEs/ADRs (frequency, type, severity, duration), changes in vital signs, physical examination findings, 12-lead ECG findings, clinically significant laboratory parameter changes, assessment for suicidal ideation/behavior; plasma concentrations measured by PK sampling at predefined timepoints."}

Secondary endpoints

• {"endpoint_text":"- Change from baseline to end of the Maintenance Period (Day 84) in seizure frequency from daily seizure electronic diary (eDiary)","definition_or_measurement_approach":"Seizure frequency measured via daily seizure electronic diary (eDiary); change from baseline to Day 84 maintenance period."}
• {"endpoint_text":"- Change from baseline to end of Part B in seizure frequency from daily seizure eDiary","definition_or_measurement_approach":"Seizure frequency measured via daily seizure electronic diary (eDiary); change from baseline to end of Part B."}
• {"endpoint_text":"- Percent change from baseline to end of treatment (Part A and Part B) in video electroencephalogram (V-EEG) seizure burden (e.g., seizure type, severity, and frequency recorded during V-EEGs)","definition_or_measurement_approach":"Seizure burden assessed by video-EEG recordings (V-EEG) comparing baseline to end of treatment (Part A and Part B); includes seizure type, severity and frequency recorded during V-EEGs."}
• {"endpoint_text":"- Number of seizure free days and longest period with no seizures from baseline to end of treatment","definition_or_measurement_approach":"Number of seizure-free days and longest seizure-free period recorded from baseline to end of treatment (data source: eDiary and clinical assessments as per protocol)."}
• {"endpoint_text":"- Change from baseline to end of treatment (Part A and Part B) in behavioral features as measured by the aberrant behavior checklist-community (ABC-2C), as well as other disorder features as measured by 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)","definition_or_measurement_approach":"Behavioral and quality-of-life endpoints measured using standardized instruments: ABC-2C for behavior, PedsQL for quality of life, CBI for caregiver burden, CaGI-C and CGI-C for global impressions; comparisons from baseline to end of treatment (Parts A and B)."}

Methods

• Digital Banner Adverts (FCD/TSC) - online banner advertisements (documents: Digital Banner Adverts FCD/TSC).
• Google-Facebook Adverts (FCD/TSC) - social media advertising materials (documents: Google-Facebook Adverts_FCD and _TSC).
• Advocacy Alert Infographic (FCD/TSC) - materials for advocacy distribution to raise awareness among patient groups.
• Patient Brochure and Patient Facing Website - informational materials/web content for potential participants and caregivers.
• Recruitment and Informed Consent Procedure forms and Welcome Booklets / Thank you cards - site-level printed recruitment/support materials and guidance for consent process.
• eDiary (electronic seizure diary) deployment as part of participation requirements (documents indicate use of eDiary vendor Signant Health).

Italy

Earliest CTIS Part Ii Submission Date

21-09-2023

Latest Decision Or Authorization Date

28-04-2026

Processing Time Days

950

Number Of Sites

4

Number Of Participants

10

Netherlands

Earliest CTIS Part Ii Submission Date

04-07-2024

Latest Decision Or Authorization Date

27-04-2026

Processing Time Days

662

Number Of Sites

1

Number Of Participants

1

Belgium

Earliest CTIS Part Ii Submission Date

09-07-2024

Latest Decision Or Authorization Date

27-04-2026

Processing Time Days

657

Number Of Sites

2

Number Of Participants

4

Spain

Earliest CTIS Part Ii Submission Date

02-11-2023

Latest Decision Or Authorization Date

29-04-2026

Processing Time Days

909

Number Of Sites

4

Number Of Participants

9

Poland

Earliest CTIS Part Ii Submission Date

07-12-2023

Latest Decision Or Authorization Date

28-04-2026

Processing Time Days

873

Number Of Sites

4

Number Of Participants

4

Primary sponsor

Full Name

Grin Therapeutics Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Innovative Trials Limited

Responsibilities

Patient Recruitment

Name

Premier Research International LLC

Name

Calyx

Name

ICON Bioanalytical Laboratory

Third parties

• {"country":"United States","full_name":"Epilepsy Study Consortium Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Innovative Trials Limited","duties_or_roles":"Patient Recruitment","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Calyx","duties_or_roles":"","organisation_type":"Industry"}
• {"country":"Netherlands","full_name":"ICON Bioanalytical Laboratory","duties_or_roles":"","organisation_type":"Industry"}
• {"country":"Belgium","full_name":"Clouds of Care","duties_or_roles":"VEEG vendor","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Signant Health Global LLC","duties_or_roles":"eDiary","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Acm Medical Laboratory Inc.","duties_or_roles":"","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United Kingdom","full_name":"Acm Global Central Laboratory Limited","duties_or_roles":"","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United Kingdom","full_name":"MD Group","duties_or_roles":"Patient Recruitment","organisation_type":"Health care"}
• {"country":"United Kingdom","full_name":"Etymax Limited","duties_or_roles":"study documents translations","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Premier Research International LLC","duties_or_roles":"","organisation_type":"Pharmaceutical company"}