Open-label Extension to Protocol 1042-0500

Study Overview
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Brief Summary
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To allow open-label extension to patients who have completed Protocol 1042-0500

Detailed Description
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Patient should have completed all scheduled clinical study visits in the double blind, controlled trial (Protocol 1042-0500) and have been deemed eligible (had a response to treatment) by the Investigator. Male or female, with a diagnosis of IS with a video EEG (vEEG) recording confirming the diagnosis. There will be a total of 14 visits over 99(+or-1)week. A 24-hr vEEG is only required if the subject has been spasm-free for more than 24-hrs.

Official Title
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An Open-label Clinical Study to Evaluate the Safety and Antiepileptic Activity of Ganaxolone in Treatment of Patients Diagnosed With Infantile Spasms.

Conditions
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Infantile Spasms

Intervention / Treatment
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* Drug: Ganaxolone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have completed all scheduled clinical study visits in the previous Protocol 1042 0500 and have been deemed eligible (no SAEs thought to be drug related and had a response to treatment) by the Investigator. Be diagnosed with IS regardless of etiology. Diagnostic Criteria: Seizures consisting of single or repetitive short muscular contractions leading to flexion or extension. Spasms may be characterized as tonic or myoclonic contractions, may occur singly or in clusters, and typically occur bilaterally and symmetrically. The EEG pattern must be consistent with the diagnosis of IS (hypsarrhythmia, modified hypsarrhythmia, multifocal spike wave discharges, etc). Have a 24 hour vEEG recording confirming the diagnosis of IS. Have had a magnetic resonance imaging (MRI) performed to determine any possible causes of IS. Have been previously treated with 3 AEDs or fewer. Have a parent/guardian who is properly informed of the nature and potential risks and benefits of the clinical study, is willing and capable of complying with all clinical study procedures, and has given informed consent in writing prior to entering the clinical study. Exclusion Criteria: Current treatment with more than 2 concomitant AEDs. Have an active CNS infection, demyelinating disease, degenerative neurological disease, or CNS disease deemed progressive (with the exception of tuberous sclerosis) as evaluated by brain MRI. Have any disease or condition (medical or surgical) at Screening that might compromise the hematologic, cardiovascular, pulmonary, renal, GI, or hepatic systems; or other conditions that might interfere with the absorption, distribution, metabolism, or excretion of the investigational product, or would place the subject at increased risk. Aspartate transaminase (AST), alanine transaminase (ALT), or total bilirubin greater than 4 times the upper limit of laboratory normal or any clinical laboratory value deemed clinically significant by the Investigator. History of recurrent status epilepticus. Have been exposed to any other investigational drug within 30 days prior to enrollment.

Ages Eligible for Study
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Minimum Age: 4 Months
Maximum Age: 24 Months

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ganaxolone<br> | Drug: Ganaxolone<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Were Free of Spasms | Clinical spasms were determined by video-electroencephalography (VEEG). The number of participants with spasm-free duration have been presented. | Weeks 4 through Week 96 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Frequency of Spasm Clusters | Infantile spasms that come one after another in a cluster and lasts several minutes are called Spasm Clusters. Spasm clusters were determined by a 24-hour video-electroencephalography (vEEG). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Baseline was defined as the Day 0 assessment prior to ganaxolone dosing in Protocol 1042-0500. | Baseline and Week 4 through Week 32 | 
| Change From Baseline in Frequency of Individual Spasm | Individual Spasm are seizures that may last only a second or two and were determined by a 24-hour video-electroencephalography (vEEG). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Baseline was defined as the Day 0 assessment prior to ganaxolone dosing in Protocol 1042-0500. | Baseline and Week 4 through Week 32 | 
| Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Caregiver global assessment of seizure severity and response to treatment rated the participants' based on 7 clinical factors: seizure frequency, duration, and intensity; adverse experiences; social, intellectual, and motor functioning. Using a 7-point scale ([1] marked improvement, [2] moderate improvement, [3] slight improvement, [4] no change from baseline, [5] slight worsening, [6] moderate worsening, or [7] marked worsening). Higher score indicated worse symptoms. The assessment compared the participants' current status to their condition prior to initiating study medication. | Week 4 through Week 32 | 
| Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | The investigators rated the participants' overall clinical status based on 7 clinical factors: seizure frequency, duration, and intensity; adverse experiences; social, intellectual, and motor functioning. Using a 7-point scale ([1] marked improvement, [2] moderate improvement, [3] slight improvement, [4] no change from baseline, [5] slight worsening, [6] moderate worsening, or [7] marked worsening). Higher score indicated worse symptoms. The investigators assessed the participants' status compared to their condition prior to initiating study medication. | Week 4 through Week 32 | 
| Number of Participants With Spasm-free Durations | Spasm-free duration is defined as total number of spasm-free days recorded in the spasm/seizure diary. Parents/Guardians or nursing staff maintained a spasm/seizure diary to record the number and type of seizures each day, including spasms, throughout the entire study. The number of participants with spasm-free duration of at least 24 hours have been presented. | Week 4 through Week 32 | 
| Number of Participants With Absence of Spasms | Absence of spasms is defined as percentage of total spasm-free days during a visit period=100%. Parents/Guardians or nursing staff maintained a spasm/seizure diary to record the number and type of seizures each day, including spasms, throughout the entire study. The participants achieving absence of spasms have been presented. | Week 4 through Week 32 | 
| Developmental Assessment Using Denver-II Developmental Test | Denver-II Developmental Test measures a child's development in several areas:Personal-Social,Fine Motor-Adaptive,Language,and Gross Motor,from birth to 6 years old.It consists of 125 items that are organized into subscales and scored as pass,fail,or refused.To evaluate a child's progress,test compares their performance to a normative sample of children of same age.For each item,age at which 90% of children in normative sample pass it is determined.Derived score for each subscale is sum of item scores and represents difference between child's chronological age and age at which 90% of children in normative sample pass the items in that subscale.A higher derived score on a subscale indicates better performance on items in that subscale relative to other children of same age who have taken the test.Among subscales,Personal-Social subscale ranges from -16 months to 24 months;others range from - 12 months to 24 months.All subscales have a population mean of 0 and a standard deviation of 3. | Week 8 through Week 32 | 
| Percentage of Total Spasm-free Days and Cumulative Spasm-free Days as Determined From the Seizure Diary. | Percentage of total spasm-free days during a visit period is defined as total number of spasm free days as recorded in the Seizure Diary/ total number of days during that period, multiplied by 100. Percentage of cumulative total spasm-free days during a visit period is defined as sum of total number of spasm-free days during this period as recorded in the Seizure Diary/ total number of days in the treatment period, multiplied by 100. | Weeks 4 through Week 32 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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infantile spasms, anticonvulsant, pediatric epilepsy, West Syndrome, epileptic spasms