Back to resultsOpen-label Extension to Protocol 1042-0500
Primary Purpose
Infantile Spasms
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Ganaxolone
Sponsored by
About this trial
This is an interventional treatment trial for Infantile Spasms focused on measuring infantile spasms, anticonvulsant, pediatric epilepsy, West Syndrome, epileptic spasms
Eligibility Criteria
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.
Sites / Locations
- Children's Hospital of Los Angeles
- Mattel Children's Hospital at UCLA
- Children's National Medical Center
- Miami Children's Hospital, The Brain Institute
- Child Neurology Center of Nrothwest Florida, P.A.
- University of Chicago Comer Children's Hospital
- Minnesota Epilepsy Group, P.A.
- Montefiore Medical Center- Albert Einstein College of Medicine
- Le Bonheur Children's Medical Center
- Dallas Pediatric Neurology Associates
- Texas Children's Hospital
- Virginia Commonwealth University Health Systems
- Children's Hospital and Regional Medical Center
- Children's Hospital of Wisconsin
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
ganaxolone
Arm Description
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
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.
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.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00442104
Brief Title
Open-label Extension to Protocol 1042-0500
Official Title
An Open-label Clinical Study to Evaluate the Safety and Antiepileptic Activity of Ganaxolone in Treatment of Patients Diagnosed With Infantile Spasms.
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Terminated
Why Stopped
Sponsor's decision
Study Start Date
January 2007 (Actual)
Primary Completion Date
March 2009 (Actual)
Study Completion Date
March 2009 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Marinus Pharmaceuticals
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
To allow open-label extension to patients who have completed Protocol 1042-0500
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Infantile Spasms
Keywords
infantile spasms, anticonvulsant, pediatric epilepsy, West Syndrome, epileptic spasms
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
54 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ganaxolone
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Ganaxolone
Primary Outcome Measure Information:
Title
Percentage of Participants Who Were Free of Spasms
Description
Clinical spasms were determined by video-electroencephalography (VEEG). The number of participants with spasm-free duration have been presented.
Time Frame
Weeks 4 through Week 96
Secondary Outcome Measure Information:
Title
Change From Baseline in Frequency of Spasm Clusters
Description
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.
Time Frame
Baseline and Week 4 through Week 32
Title
Change From Baseline in Frequency of Individual Spasm
Description
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.
Time Frame
Baseline and Week 4 through Week 32
Title
Number of Participants With Change in Clinical Status on Caregiver's Global Assessment
Description
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.
Time Frame
Week 4 through Week 32
Title
Number of Participants With Change in Clinical Status on the Investigator's Global Assessment
Description
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.
Time Frame
Week 4 through Week 32
Title
Number of Participants With Spasm-free Durations
Description
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.
Time Frame
Week 4 through Week 32
Title
Number of Participants With Absence of Spasms
Description
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.
Time Frame
Week 4 through Week 32
Title
Developmental Assessment Using Denver-II Developmental Test
Description
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.
Time Frame
Week 8 through Week 32
Title
Percentage of Total Spasm-free Days and Cumulative Spasm-free Days as Determined From the Seizure Diary.
Description
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.
Time Frame
Weeks 4 through Week 32
10. Eligibility
Sex
All
Minimum Age & Unit of Time
4 Months
Maximum Age & Unit of Time
24 Months
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Facility Information:
Facility Name
Children's Hospital of Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Facility Name
Mattel Children's Hospital at UCLA
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Children's National Medical Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Facility Name
Miami Children's Hospital, The Brain Institute
City
Miami
State/Province
Florida
ZIP/Postal Code
33155
Country
United States
Facility Name
Child Neurology Center of Nrothwest Florida, P.A.
City
Pensacola
State/Province
Florida
ZIP/Postal Code
32504
Country
United States
Facility Name
University of Chicago Comer Children's Hospital
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Minnesota Epilepsy Group, P.A.
City
Saint Paul
State/Province
Minnesota
ZIP/Postal Code
55102
Country
United States
Facility Name
Montefiore Medical Center- Albert Einstein College of Medicine
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
Le Bonheur Children's Medical Center
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38105
Country
United States
Facility Name
Dallas Pediatric Neurology Associates
City
Dallas
State/Province
Texas
ZIP/Postal Code
75230
Country
United States
Facility Name
Texas Children's Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Virginia Commonwealth University Health Systems
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
Facility Name
Children's Hospital and Regional Medical Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States
Facility Name
Children's Hospital of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53201
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Open-label Extension to Protocol 1042-0500
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