Tuberous Sclerosis Complex MedDRA version: 21.0 Level: PT Classification code 10080584 Term: Tuberous sclerosis complex System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Sponsors
Noema Pharma
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients must meet all the following criteria for study entry: 1. Ability and willingness to provide informed assent or written consent or consent from their legal representative and willingness to comply with the study procedures. 2. Fluency in the language of the investigator, study staff and the informed assent or consent form when applicable. 3. Age 5 to 30 years at study entry 4. A documented history of TSC, diagnosed according to the International Tuberous Sclerosis Complex diagnostic criteria of 2021 and including a record of either genetic test or MRI/CT scan documenting tumors. 5. Continued seizures associated with TSC (including atypical absences, atonic, focal, tonic, tonic-clonic or myoclonic) despite adequate dosage of at least 1 or more appropriate AEDs, within approximately the previous year. 6. Refractory seizure history, defined as 3 or more countable seizures per month on average over the last year 3 months and at least 3 countable seizures within the past 28 days. 7. Currently receiving 1 or more AEDs with no change in doses in the 30 days prior to study entry and no anticipated dose changes during study participation. 8. All medications or interventions for epilepsy (including ketogenic diet and any neurostimulation devices for epilepsy) must be stable for 30 days prior to study entry and the patient must be willing to maintain a stable regimen throughout the study. The ketogenic diet and neurostimulation treatments are not considered AEDs for the purpose of this study. 9. Patients or their caregiver must be willing to complete daily PRO assessments 10. For female patients of childbearing potential: a. willingness to undergo serum or urinary pregnancy testing at screening and during the trial period. b. willingness to use contraception as defined in Appendix D. Are the trial subjects under 18? yes Number of subjects for this age range: 45 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 20 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Patients who meet any of the following criteria will be excluded from study participation: 1. Etiology of a patient’s seizures is a progressive neurologic disease other than TSC. 2. Anoxic episode requiring resuscitation within 6 months of screening. 3. Patient weight below 15kg. 4. Clinically significant unstable medical conditions other than epilepsy including, but not limited to, cardiovascular, gastrointestinal, renal, hepatic, neurological, musculoskeletal, infectious, endocrine, metabolic, hematological, psychiatric, or other major physical impairment that is not stable in the opinion of the investigator and could affect the safety of the patient throughout the study, influence the findings of the study or their interpretation, or might impede the patient’s ability to complete the entire duration of the study. 5. Any clinically significant abnormal findings in physical examination, vital signs, hematology, clinical chemistry, or urinalysis during screening which, in the opinion of the investigator, may put the patient at risk because of their participation in the study, or might influence the results of the study, or the patient’s ability to complete the entire duration of the study. 6. Clinically relevant symptoms or a clinically significant illness in the 4 weeks prior to screening or randomization, other than epilepsy. 7. Current or past use of recreational or medicinal cannabis within the 3 months prior to study entry and unwillingness to abstain for the duration of the study or a positive result on a urine tetrahydrocannabinol (THC) panel test. (Cannabidoil is an AED and is therefore allowed for the treatment of TSC). 8. Participation in a clinical trial involving another investigational product (IP) in the previous 6 months or at any time in a gene therapy clinical trial. 9. Brain surgery =6 months prior to study entry for all ages, and for patients<12-year-old, brain surgery for epilepsy treatment prior to study entry). 10. Patient has bipolar disorder. 11. Patient is currently taking long-term systemic steroids (excluding inhaled medication for asthma treatment) or any other daily medication known to exacerbate epilepsy. An exception will be made for prophylactic medication such as medications for idiopathic nephrotic syndrome or asthma. 12. Pregnancy or lactation. 13. Participants with a history of an allergic reaction or hypersensitivity to constituents of the study drug (and its excipients) and/or other products in the same class. 14. Current alcohol abuse/dependence.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of a double-blind, daily basimglurant administration, adjunctive to ongoing anticonvulsive therapy compared with placebo adjunctive to ongoing anticonvulsive therapy in patients with Tuberous Sclerosis Complex (TSC). ;Secondary Objective: -To evaluate the impact of treatment on functioning at school and during social activities. -To determine the effect of basimglurant on the severity of symptoms of TSC. -To determine the longest seizure free interval (i.e., seizure free days). -To evaluate the number of patients considered treatment responders. Other Secondary Objectives: - To evaluate the safety of basimglurant in children, adolescents, and young adults with seizures associated with TSC. - To investigate the proportion of patients tolerating each dose during dose escalation. - To investigate long-term safety of basimglurant in children, adolescents, and young adults with seizures associated with TSC;Primary end point(s): Estimand 1a (Primary): - Ratio of geometric means of monthly seizure counts in Periods 2 and 4 between basimglurant and placebo in children, adolescents, and young adults with seizures associated with TSC, assuming hospitalization due to COVID-19 or death would not have occurred, irrespective of treatment discontinuation and use of prohibited medications Primary Endpoint: Monthly seizure counts of countable seizure types(per 28 days) during the 12-week treatment period in Period 2 and Period 4.;Timepoint(s) of evaluation of this end point: Monthly seizure counts (per 28 days) during the 12-week treatment period in Period 2 and Period 4. The Holm procedure (Holm 1979) will be used within the test family at the end of the hierarchy for the responses in monthly seizure counts. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Changes from baseline in Sheehan Disability Scale(SDS) score at Week 16 in Period 2 and at Week 30 in Period 4 - Caregiver Global Impression of Change (CGIC) score at Week 16 in Period 2 and Week 30 in Period 4. - Monthly seizure free days (per 28 days) during the 12-week treatment period in Period 2 and Period 4. -Seizure 25% response defined as =25% reduction from baseline in monthly seizure counts of countable seizure types during the 12-week treatment period in Periods 2 and 4. -Seizure 50% response defined as =50% reduction from baseline in monthly seizure counts of countable seizure types during the 12-week treatment period in Periods 2 and 4. -Seizure 75% response defined as =75% reduction from baseline in monthly seizure counts of countable seizure types during the 12-week treatment period in Periods 2 and 4. Other Secondary Endpoints: - Adverse events, -Absolute values and changes from baseline in vital signs, physical examination, electrocardiograms, and clinical laboratory test parameters. - Treatment delays, dose reductions, and dose discontinuations. - S-STS score for suicidal ideation. - Seizure types. - Escalation (Yes/No) to each dose level during the dose escalation in Periods 2 and 4. - Toleration (Yes/No) of each dose level during the dose escalation in Periods 2 and 4. -Adverse events and other safety and tolerability parameters during the OLE period.;Timepoint(s) of evaluation of this end point: -Changes from baseline in SDS score at Week 16 in Period 2 and at Week 30 in Period 4 -CGIC score at Week 16 in Period 2 and at Week 30 in Period 4 -Monthly seizure-free days during the 12-week treatment period in Periods 2 and 4 -Response in monthly seizure counts | — |
Countries
India, Israel, Italy, Poland, Spain, Türkiye, United Kingdom, United States
Contacts
Public ContactVP, Pediatric Programs
Noema Pharma
Outcome results
None listed