Tuberous Sclerosis Complex
Conditions
Keywords
Basimglurant, TSC, Seizures, NOE-101
Brief summary
The study intends to show that basimglurant (NOE-101) provides effective seizure control in children, adolescents and young adults with Tuberous Sclerosis Complex (TSC).
Detailed description
The study drug (NOE-101, basimglurant) is a potent inhibitor of metabotropic glutamate receptor 5 (mGluR5) which controls a wide range of processes in the brain, spinal cord, retina, and peripheral nervous system. In animal studies, the inhibition of this receptor has shown therapeutic potential for the treatment of Tuberous Sclerosis Complex (TSC). This receptor's inhibition decreases the frequency of seizures. In previous clinical trials, the study drug has shown an advantageous safety profile in children and adolescents. The objective of this study is to find an optimal dose at which the study drug will lead to a decrease in the duration, frequency and intensity of seizures in children, adolescents and young adults with TSC, while being well tolerated. All patients who positively respond and tolerate the medicine will be offered the possibility to continue in an open label extension.
Interventions
DRUGBasimglurant with crossover to Placebo
Basimglurant with crossover to Placebo
DRUGPlacebo with crossover to Basimglurant
Placebo with crossover to Basimglurant
Sponsors
Noema Pharma AG
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Intervention model description
This is a multi-center, randomized, double-blind, placebo-controlled, 30-week, cross-over (Part A) followed by a 52-week open-label extension (OLE) (Part B) study.
Eligibility
Sex/Gender
ALL
Age
5 Years to 30 Years
Healthy volunteers
No
Inclusion criteria
(summary): * Ability and willingness to provide informed assent or written consent or consent from their legal representative. * Fluency in the language of the study staff * Age 5 to 30 years at study entry * A documented history of TSC * Refractory seizure history * Currently receiving one or more anti-epileptic drugs (AEDs) * Stable medications or interventions for epilepsy * Willingness to complete Patient Reported Outcome assessments * For female patients of childbearing potential: 1. Willingness to undergo serum or urinary pregnancy testing at screening and during the trial period. 2. Willingness to use contraception.
Exclusion criteria
(summary): * Neurologic disease other than TSC * Recent anoxic episode * Patient weight below 15kg * Clinically significant unstable medical condition(s) * Pregnancy or lactation
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Mean percentage in monthly seizure frequency during the maintenance dosing in Period 2 (Weeks 13 to 16) and Period 4 (Weeks 27-30). | 30 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Longest seizure free interval (i.e., seizure free days). | 30 weeks | — |
| Change in the severity of symptoms of TSC as measured by Caregiver Global Impression of Change (CGIC) score during maintenance dosing in Period 2 (Weeks 13 to 16) and Period 4 (Weeks 27-30) compared to Baseline. | 30 weeks | — |
| Change in the Sheehan Disability Scale during maintenance dosing in Period 2 (Weeks 13 to 16) and Period 4 (Weeks 27-30) compared to baseline. | 30 weeks | — |
| Safety of the study drug in children, adolescents and young adults with seizures associated with TSC. | 82 weeks | Measured in terms of incidence, nature, and severity of adverse events, vital signs, physical examination, clinical chemistry, hematology, electrocardiograms, and urinalysis, as well as treatment delays, dose reductions, and dose discontinuations. In addition, suicidal ideation will be assessed using S-STS. |
| Number of patients considered treatment responders. | 30 weeks | — |
Other
| Measure | Time frame |
|---|---|
| Intensity of seizures detected by the wearable device evaluated as the change from Baseline compared to study treatment Periods 1 and 4. | 30 weeks |
| Frequency of seizures detected by the wearable device evaluated as the change from Baseline compared to study treatment in Period 1 (weeks 13 to 16) and Period 4 (weeks 27 to 30). | 30 weeks |
| Change in seriousness of disease as assessed by Most Impactful Symptoms Scale in Periods 2 (weeks 13 to 16) and Period 4 (weeks 27 to 30) compared to baseline. | 30 weeks |
Countries
India, Israel, Italy, Poland, Spain, Turkey (Türkiye), United Kingdom, United States
Outcome results
None listed