Basimglurant in Children and Adolescents With TSC
Study Details
Study Description
Brief Summary
The study intends to show that basimglurant provides effective seizure control in children and adolescents with Tuberous Sclerosis Complex (TSC).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
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 and adolescents 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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Arm A (Basimglurant to Placebo) Basimglurant to Placebo |
Drug: Basimglurant with crossover to Placebo
Basimglurant with crossover to Placebo
|
| Placebo Comparator: Arm B (Placebo to Basimglurant) Placebo to Basimglurant |
Drug: Placebo with crossover to Basimglurant
Placebo with crossover to Basimglurant
|
Outcome Measures
Primary Outcome Measures
- Mean percentage change from baseline of seizure frequency during the maintenance dosing in Period 2 (Weeks 13 to 16) and Period 4 (Weeks 27-30). [30 weeks]
Secondary Outcome Measures
- 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 TSCas 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]
- Changes 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 and adolescents 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.
Other Outcome Measures
- 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]
- 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]
- Intensity of seizures detected by the wearable device evaluated as the change from Baseline compared to study treatment Periods 1 and 4. [30 weeks]
Eligibility Criteria
Criteria
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 18 years
-
A documented history of TSC,
-
Refractory seizure treatment status
-
Currently receiving one or more anti-epileptic drugs (AEDs)
-
Stable medications or interventions for epilepsy
-
Willingness to complete Patient Reported Outcome
-
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | David Geffen School of Medicine at UCLA (Site #: 101) | Los Angeles | California | United States | 90095 |
| 2 | Kennedy Krieger Institute (Site #: 110) | Baltimore | Maryland | United States | 21205 |
| 3 | Boston Children's Hospital (Site #: 102) | Boston | Massachusetts | United States | 02115-5724 |
| 4 | Helen DeVos Children Hospital (Site #: 112) | Grand Rapids | Michigan | United States | 49503-2560 |
| 5 | William Beaumont Hospital - Royal Oak (Site #: 104) | Royal Oak | Michigan | United States | 48073-6712 |
| 6 | Minnesota Epilepsy Group PA (Site #: 105) | Roseville | Minnesota | United States | 55113-1306 |
| 7 | Boston Children's Health Physicians (BCHP) (Site #: 111) | Hawthorne | New York | United States | 10532 |
| 8 | Duke Children's Hospital and Health Center (Site #: 106) | Durham | North Carolina | United States | 27705-4699 |
| 9 | University Hospitals Cleveland Medical Center, Rainbow Babies and Childrens Hospital (Site #: 107) | Cleveland | Ohio | United States | 44106-1716 |
| 10 | Texas Scottish Rite Hospital For Children (Site #: 113) | Dallas | Texas | United States | 75219-3924 |
| 11 | The University of Texas Medical School at Houston (Site #: 103) | Houston | Texas | United States | 77030-3000 |
| 12 | Multicare Health System (Site#: 109) | Tacoma | Washington | United States | 98405-4048 |
Sponsors and Collaborators
- Noema Pharma AG
Investigators
- Study Director: Renata Lazarova, MD, Noema Pharma AG
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NOE-TSC-201