Refractory Epilepsy
Conditions
Brief summary
This is a Phase 2 double-blind, randomized, placebo-controlled study to assess the safety and efficacy of ICV delivery of CT-010 via an implantable pump and a cranial port and dual lumen catheter (CIC) in subjects with focal seizures, with temporal lobe onset with or without secondary generalization. Up to 70 subjects will be enrolled. Eligible subjects will be randomized in a 1:1 ratio to either CT-010 or placebo treatment. Up to 20 clinical centers will be enrolled.
Detailed description
Epilepsy patients that are refractory to oral anti-epileptic drug (AED) treatment have significantly higher mortality, higher morbidity, higher economic costs and diminished quality of life compared to those who suffer from epilepsy that can be adequately controlled with medical management. Current options for refractory patients include neurosurgical brain resection, responsive neurostimulation, and vagal nerve stimulation. None of these options is satisfactory due to the low applicability of surgery for patients with poorly localized or multifocal seizures and the limited success of currently available alternative treatment options. In this study, patients with medically refractory focal epilepsy will be treated with intracerebroventricular (ICV) administration of CT-010, a reformulation of valproate, using an implantable drug pump system. This is a randomized, double-blind Phase 2 study evaluating the efficacy and safety of this therapy. Clinical assessments, adverse events (AEs), seizure diaries, concomitant medications, blood samples and cerebrospinal fluid (CSF) will be collected and reviewed at designated time points. Magnetic resonance imaging (MRI) and electroencephalography (EEG) will also be performed. Subjects will have their surgery, dose changes and pharmacokinetics performed in an inpatient setting. Subjects will be enrolled based on Inclusion/Exclusion Criteria and undergo a 6-week baseline period confirming and establishing monthly seizure rate. Following the baseline period subjects will undergo system implant and a 1-month implant recovery period. Following successful implant and recovery subjects will be randomized to either active therapy or placebo for a 3-month blinded evaluation period. At the conclusion of the blinded evaluation period, subjects will roll into an Open Label Extension Period, CLN100P.02. Subjects that were randomized to placebo will receive active therapy during CLN100P.02.
Interventions
COMBINATION_PRODUCTICV delivery of CT-010 via an implantable pump and a cranial port and dual lumen catheter (CIC)
Subjects will be implanted with a drug delivery pump and catheters leading to the ICV space allowing delivery of CT-010.
COMBINATION_PRODUCTPlacebo delivery via an implantable pump and a cranial port and dual lumen catheter (CIC)
Subjects will be implanted with a drug delivery pump and catheters leading to the ICV space allowing delivery of a placebo (saline).
Sponsors
Cerebral Therapeutics LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
Inclusion/
Exclusion criteria
\- For a subject to be eligible for this study, he or she must meet ALL of the following criteria: 1. Subject is male or female between the ages of 18 to 70 years old. 2. Subject is considered an appropriate surgical candidate by the implanting Neurosurgeon. 3. Subject has had confirmed refractory epilepsy for a minimum of 2 years, with unilateral or bilateral temporal lobe involvement with no more than 2 known extratemporal foci. 4. In the opinion of the Investigator, subject has disabling seizures. 5. Subject has had at least one seizure recorded by EEG or video EEG or invasive monitoring within the past 3 years consistent with focal temporal lobe seizures (a normal interictal EEG is consistent with focal seizures) 6. Subject has not achieved effective results previously from at least 3 AEDs in single or combination. An AED may be counted as failed medication if subject has been on it for at least 3-months and is still refractory. 7. Subject failed to obtain an adequate intake of oral valproate of at least 1,000 mgs a day and/or to achieve serum level of at least 60 µg/mL or in the opinion of the Investigator is not a candidate for oral valproate (including subject preference) 8. Per medical history, for the 3 months before informed consent an average of six or more disabling focal seizures of temporal lobe onset, with or without secondary generalization, per month. 9. Subject has seizures that are distinct, stereotypical events that can be reliably counted, in the opinion of the Investigator, by the subject or caregiver. 10. Subject understands study procedures and has voluntarily provided signed, informed consent in accordance with institutional and local regulatory requirements. 11. Subject agrees to maintain the diary for the duration of the study alone or with the assistance of a competent individual. Subjects must NOT meet any of the following
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Median frequency of total monthly seizures during the Primary Evaluation Period as compared to the Baseline Period as well as a comparison of this Baseline Period/Primary Evaluation Period ratio for the active vs. placebo treatment groups | 84 days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Seizure Severity Questionnaire (SSQ) | 84 days | Evaluation of change in seizure severity during the blinded period by evaluating any change in the SSQ scores between baseline and Day 84 of blinded period where a lower score is an improvement in condition. |
| QOLIE-10 | 84 days | Evaluation of change in quality of life during the blinded period by evaluating change in QOLIE-10 scores between baseline and 84-day evaluations. |
| Patient Global Impression of Change (PGIC) | 84 days | Evaluation of subjects impression of therapy efficacy through the PGIC questionnaire at the conclusion of the blinded period. Scale is a single question with a score of 1-7 with a higher score representing a greater improvement in condition. The score is also captured as a VAS of 1-10 again with a higher score representing a greater improvement in condition. |
| BDI | 84 days | Evaluation of depression through the BDI questionnaire |
| BAI | 84 days | Evaluation of anxiety through the BAI questionnaire |
Countries
Australia, Israel
Outcome results
None listed