A Pilot Study: Focused Ultrasound Thalamotomy for the Prevention of Secondary Generalization in Focal Onset Epilepsy
Purpose of the Study: The purpose of this study is to assess the safety and feasibility of Magnetic Resonance Imaging-guided focused ultrasound (MRgFUS) in patients with epilepsy whose medicines are not working well. The ExAblate transcranial system is the name of the device that will be used to create and send ultrasound waves through the scalp and skull precisely to a small structure located in the center of the brain. This structure is known as the "Anterior Nucleus", and is an important region in the brain that may cause the seizures. Safety will be measured by recording and analyzing any adverse effects that may occur from the day of the experimental surgery through 12 months following the surgery.
- Disabling, medically refractory epilepsy (≥2 anti-epileptic drug failures)
- Focal onset seizures with secondary generalization; with or without primary generalized seizures.
- ≥ 3 seizures/month on average within 3 months of enrollment.
- Stable medication dosage for 3 months before enrollment.
- Anterior Nucleus (AN) identifiable on MRI (structural T1 and T2 images).
- Willing to maintain seizure diary (3 months before & 3 months after).
- Involved care provider.
- Written informed consent to participate.
- 18-65 years of age, inclusive.
- Previous seizure work-up within 12 months of enrollment date to include:
Home EEG or EMU video EEG or intracranial EEG.
Baseline neuropsychological assessment, which includes the Wechsler Advanced Clinical Solutions - Test of Premorbid Functioning (TOPF). Subjects obtaining an IQ score of ≥70 on the TOPF will be included.
High definition MRI imaging/PET imaging.
- Low seizure frequency (<3 seizures/month).
- Previous vagal nerve stimulator.
- Severe untreated neuropsychiatric disorders (untreated depression or behavioral problems).
- Recent history of drugs or alcohol abuse.
- Generalized epilepsy (Lennox Gastaut, drop attacks).
- Post infectious epilepsy (post herpetic).
- Previous corpus callosotomy.
- Significant structural brain abnormalities.
- Unable or unwilling to maintain drug dosage for 3 months post treatment.
- Pregnant or not practicing birth control method acceptable to the principal investigator.
- History of claustrophobia.
- Known allergic reaction and/or hypersensitivity to IV dye and/or IV contrasting agent(s).
- Skull Density Ratio (SDR) <0.4.
- IQ score of <70 on the Wechsler Advanced Clinical Solutions - Test of Premorbid Functioning (TOPF), a measure conducted as part of baseline neuropsychological assessment.
Study Status: Recruiting.
Sponsor: Vibhor KrishnaCollaborator: Focused Ultrasound Foundation
A Trial of the Efficacy and Safety of CVL-865 as Adjunctive Therapy in the Treatment of Focal Onset Seizures
Purpose of the Study: The purpose of this study is to assess the efficacy, safety, and tolerability profile of CVL-865 as adjunctive treatment in participants with drug-resistant focal onset seizures.
- Participants with a diagnosis of epilepsy with focal onset, as defined in the International League Against Epilepsy (ILAE) Classification of Seizures, focal aware (except participants with only focal aware seizures without a motor component), focal impaired awareness, and focal to bilateral tonic-clonic seizures for at least 2 years prior to signing the Informed Consent Form (ICF)
- Participants must have history of an average of 4 or more spontaneous and observable focal onset, as defined in the ILAE Classification of Seizures, focal aware (except participants with only focal aware seizures without a motor component), focal impaired awareness, and focal to bilateral tonic-clonic seizures per 28-day period for at least 3 months (84 days) prior to signing the ICF
- Participants who have tried and failed at least 2 appropriate Anti- epileptic drugs (AEDs) in the past and also currently taking 1 to 3 permitted AEDs at a stable dose for 4 Weeks prior to the Screening Visit
- Participants with a minimum of 8 focal onset, focal aware, focal impaired awareness, or focal to bilateral tonic-clonic seizures during the 8 week baseline period with no 21-day period free of any of these seizure types
- Participants must have had magnetic resonance imaging or contrast enhance computed tomography scan of the brain that demonstrated no progressive structural central nervous system abnormality at the time of the diagnosis of epilepsy
- Participants must have a body mass index (BMI) of 17.5 to 40.0 kilogram per meter square (kg/m^2) and a total body weight greater than (>) 50 kilograms (kg) [110 pounds (lbs)]
- Women of childbearing potential must agree to use an effective method of contraception from signing of informed consent throughout the duration of the study and for 30 days post last dose
- Male must agree to use condom during treatment and until the end of relevant systemic exposure in the male participant for 94 days following the last dose with Investigational Manufacturing Product (IMP)
- Participants with (genetic) idiopathic generalized epilepsies or combined generalized and focal epilepsies, including a history of Lennox-Gastaut Syndrome
- Participants with a history of seizures over the past 12 months that occur at such a high frequency they cannot be counted (eg, repetitive seizures, cluster seizures)
- Participants with a history of psychogenic non-epileptic seizures within the year prior to signing the ICF
- Participants with a history of status epilepticus within 5 years prior to signing the ICF
- Participants with a history of neurosurgery for seizures less than 1 year prior to signing the ICF, or radiosurgery less than 2 years prior to signing the ICF
- Participants with a current history of significant cardiovascular, pulmonary, gastrointestinal, renal, hepatic, metabolic, hematological, immunological, or neurological (excluding focal onset epilepsy) disease
- Participants who test positive for human immunodeficiency virus (HIV), hepatitis B and/or or hepatitis C infection
- Participants with a 12-lead ECG demonstrating : QT interval corrected for heart rate using Fridericia's formula >450 milliseconds (msec) (average of 3 ECGs obtained at the Screening Visit); QRS interval >120 msec at the Screening Visit assessed by central reader
- Participants with abnormal laboratory test results which includes (Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) elevated to >2 × Upper limit of normal range (ULN);
- Total bilirubin greater than or equal to (>=)1.5 × ULN; Females: Hemoglobin <11 gram per deciliter (g/dL); Males: hemoglobin <12 g/dL; White blood cell (WBC) count <3.0 x 10 power 9 per liter (10^9/L); Neutrophil count <2.0 x 10^9/L; Platelet count <150 × 10^9/L
- Use of prohibited medications as listed in the protocol in the absence of appropriate washout phase or the likelihood of requiring treatment during the study period with drugs not permitted by the study protocol
- Participants taking any drug that is a sensitive P-glycoprotein (P-gp) and Breast cancer resistance protein (BCRP) substrate
- Female participants who are breastfeeding and/or who have a positive pregnancy test result prior to receiving IMP
- Participants who are known to be allergic or hypersensitive to the IMP or any of its components
- Participants who have participated in any clinical trial within 60 days prior to signing the ICF or who have participated in more than 2 clinical trials within the year prior to signing the ICF
- Participants with difficulty swallowing
- Participants who answer "Yes" on the C-SSRS Suicidal Ideation Item 4 (Active Suicidal Ideation with Some Intent to Act, Without Specific Plan) and whose most recent episode meeting criteria for this C-SSRS Item 4 occurred within the last 6 months, OR Subjects who answer "Yes" on the C-SSRS Suicidal Ideation Item 5 (Active Suicidal Ideation with Specific Plan and Intent) and whose most recent episode meeting criteria for this CSSRS Item 5 occurred within the last 6 months OR Subjects who answer "Yes" on any of the 5 C-SSRS Suicidal Behavior Items (actual attempt, interrupted attempt, aborted attempt, preparatory acts, or behavior) and whose most recent episode meeting criteria for any of these 5 C-SSRS Suicidal Behavior Items occurred in the last 2 years
Study Status: Recruiting.
Sponsor: Cerevel Therapeutics, LLC
Phase 3 Study of Adjunctive Ganaxolone in Adults With Drug-resistant Partial Onset Seizures and Open-label Extension
Purpose of the Study: The study will evaluate the effectiveness and safety of an investigational drug-ganaxolone - on partial seizure frequency in adults with epilepsy taking a maximum of 3 antiepileptic medications (AEDs).
Description: This is a 2-cohort study consisting of 2 phases in each cohort. Phase 1 is a double-blind phase followed by phase 2, an open-label phase. Cohort 1 will provide tolerability, safety and PK information for ganaxolone 1200mg/d, 1800mg/d and placebo. Cohort 2 will investigate the efficacy, tolerability and safety of ganaxolone 1800mg/d compared to placebo. Cohort 1 (N= approximately 50) will enroll into a 67-week study consisting of a 4-week prospective baseline period plus 4 week retrospective baseline followed by two treatment phases: a 9-week randomized DB placebo-controlled treatment phase followed by a 52-week open-label (OL) treatment phase. Cohort 2 (N=150) will enroll into a 72-week study consisting of a 4-week prospective baseline period plus 4-week retrospective baseline followed by two treatment phases: a 14-week randomized DB placebo-controlled treatment phase followed by a 52-week open-label (OL) treatment phase.
Eligibility Criteria: Men and women 18 years and older with drug-resistant epilepsy with partial-onset seizures (POS), with or without secondary generalization, for two or more years, despite having been treated in the past with at least 2 approved anti-epilepsy drugs (AEDs), either alone or in combination. Participants with previous exposure or a known sensitivity to ganaxolone will be excluded.
Study Status: Open to enrollment
Principal Investigator: Amir Adeli, MD
Contact: Janet Renner, Clinical Research Manager
Funding: Marinus Pharmaceuticals