An Open-Label Study to Investigate the Safety of Single and Multiple Ascending Doses in Children and Adolescents With Dravet Syndrome
Dravet Syndrome
About this trial
This is an interventional treatment trial for Dravet Syndrome focused on measuring Pediatric epilepsy, Epileptic Encephalopathies, Refractory Myoclonic Epilepsy, Severe Myoclonic Epilepsy in Infancy
Eligibility Criteria
Inclusion Criteria:
Diagnosis of Dravet Syndrome (DS) with onset of recurrent focal motor or hemiconvulsive or generalized tonic-clonic seizures prior to 12 months of age, which are often prolonged and triggered by hyperthermia.
- No history of causal MRI lesion
- No other known etiology
- Normal development at seizure onset.
- Documented pathogenic, likely pathogenic variant, or variant of uncertain significance in the SCN1A gene associated with DS.
- Use of at least 2 prior treatments for epilepsy that either had lack of adequate seizure control (requiring an additional AED) or had to be discontinued due to an AE(s).
- Currently taking at least one AED at a dose which has been stable for at least 4 weeks prior to Screening.
- Stable epilepsy medications or interventions for epilepsy (including ketogenic diet or vagal nerve stimulator) for at least 4 weeks prior to Screening.
Exclusion Criteria:
- Known pathogenic mutation in another gene that causes epilepsy
- Currently treated with an AED acting primarily as a sodium channel blocker, as maintenance treatment, including: phenytoin, carbamazepine, oxcarbazepine, lamotrigine, lacosamide, or rufinamide.
- Clinically significant unstable medical conditions other than epilepsy.
- Clinically relevant symptoms or a clinically significant illness in the 4 weeks prior to Screening or prior to dosing on Day 1, other than epilepsy.
- History of brain or spinal cord disease (other than epilepsy or DS), or history of bacterial meningitis or brain malformation
- Spinal deformity or other condition that may alter the free flow of cerebrospinal fluid (CSF) or has an implanted CSF drainage shunt.
- Any other significant disease or disorder which, in the opinion of the Investigator, may either put the patient at risk because of participation in the study, may influence the results of the study, or may affect the patient's ability to participate in the study.
Sites / Locations
- UCSF Benioff Children's Hospital
- Children's Hospital Colorado
- Children's National Medical Center
- Nicklaus Children's Hospital
- AdventHealth Orlando
- Ann & Robert H. Lurie Children's Hospital of Chicago
- University of Iowa Hospitals and Clinics; Pediatric Specialty Clinic
- Massachusetts General Hospital - Pediatric Epilepsy Program
- University of Michigan - Mott Children's Hospital
- Mayo Clinic
- NYU Comprehensive Epilepsy Center
- Oregon Health & Science University
- Children's Hospital of Philadelphia
- Le Bonheur Children's Hospital
- Cook Children's Health Care System
- Primary Children's Hospital
- Seattle Children's Hospital
- Multicare Institute for Research and Innovation
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
Single Ascending Doses
Multiple Ascending Doses
Enrollment of patients in two age groups. A Sentinel group of 2 patients aged 13 to 18 years of age, inclusive, and an expanded group of 2 patients 2 to 12 years of age to receive single doses. There will be an option to dose up to 6 additional patients at each dose level and an option to expand the maximum tolerated dose level with 5 additional patients.
Enrollment of patients in two age groups. A Sentinel group of 2 patients aged 13 to 18 years of age, inclusive, and an expanded group of 2 patients 2 to 12 years of age to receive multiple doses. There will be an option to dose up to 6 additional patients at each dose level and an option to expand the maximum tolerated dose level with 10 additional patients.