Basimglurant in Children, Adolescents, and Young Adults With TSC

Study Overview
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Brief Summary
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The study intends to show that basimglurant provides effective seizure control in children, adolescents and young adults with Tuberous Sclerosis Complex (TSC).

Detailed Description
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The study drug (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.

Official Title
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A Phase 2B, Multicenter, 30-week, Prospective, Cross-over, Double-blind, Randomized, Placebo-controlled Study Followed by a 52-Week Open-label Extension Study to Evaluate the Efficacy and Safety of Basimglurant Adjunctive to Ongoing Anticonvulsive Therapy in Children, Adolescents, and Young Adults With Uncontrolled Seizures Associated With Tuberous Sclerosis Complex

Conditions
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Tuberous Sclerosis Complex

Intervention / Treatment
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* Drug: Basimglurant with crossover to Placebo
* Drug: Placebo with crossover to Basimglurant


Participation Criteria
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Eligibility Criteria
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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: Willingness to undergo serum or urinary pregnancy testing at screening and during the trial period. 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

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional 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.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A (Basimglurant to Placebo)<br>Basimglurant to Placebo | Drug: Basimglurant with crossover to Placebo<br>* Basimglurant with crossover to Placebo<br>|
| Placebo Comparator: Arm B (Placebo to Basimglurant)<br>Placebo to Basimglurant | Drug: Placebo with crossover to Basimglurant<br>* Placebo with crossover to Basimglurant<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients considered treatment responders. |  | 30 weeks | 
| 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. | 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. | 82 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Basimglurant, TSC, Seizures