Back to resultsA Randomized, Controlled Trial of Ganaxolone in Patients With Infantile Spasms
Primary Purpose
Infantile Spasms
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Ganaxolone
Placebo
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:
- Be diagnosed with IS (regardless of etiology- except for a progressive neurologic illness). 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 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 or fewer AEDs.
If being treated with concomitant AEDs
- Current AEDs have been at a constant daily dose for at least 2 weeks; Note: Subjects with minor dose adjustments may be allowed to enter the study after shorter periods after detailed discussion with the medical monitor.
- Have a stable clinical response/plateau for at least 2 weeks
- Are able to continue treatment with no more than 2 concomitant AEDs (ACTH, corticosteroids, felbamate, and vigabatrin are not allowed concomitantly).
- A ketogenic diet is permitted if it can be maintained for the duration of the study.
- Be a male or female, 4 to 24 months of age (inclusive)
- Have a Parent/Guardian who is properly informed of the nature and risks of the clinical study, who is willing and capable of complying with all clinical study procedures, and has given informed consent in writing prior to entering the clinical study
- Be able to participate for the full term of the clinical study.
Exclusion Criteria:
- Treatment with corticosteroids, ACTH, vigabatrin, felbamate, or any AED not approved by Regulatory Agencies, 2 weeks prior to randomization.
- Treatment with more than two AEDs at baseline.
- 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 imaging (MRI).
- Have any disease or condition (medical or surgical) at screening that might compromise the hematologic, cardiovascular, pulmonary, renal, gastrointestinal, 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 aminotransferase (AST), alanine aminotransferase (ALT), or total bilirubin greater than four times the upper limit of normal (ULN) or 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 randomization.
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 Care Center of Northwest Florida
- Child Neurology Center of Northwest Florida
- 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 System
- Children's Hospital and Regional Medical Center
- Children's Hospital of Wisconsin
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
ganaxolone
non-active drug
Arm Description
ganaxolone
placebo
Outcomes
Primary Outcome Measures
Change From Baseline in Frequency of Spasm Clusters at Day 10
Spasm clusters were determined by a 24-hour video-electroencephalography (vEEG) at Day 10. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Baseline was defined as the Day 0 assessment before study drug infusion.
Secondary Outcome Measures
Change From Baseline in Frequency of Spasm Clusters at Day 20
Spasm clusters were determined by a 24-hour vEEG at Day 20. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Baseline was defined as the Day 0 assessment before study drug infusion.
Number of Participants With Absence of Hypsarrhythmia
Absence of hypsarrhythmia was determined by 24-hour vEEG at Day 10 and Day 20.
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 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 Spasm-free Durations
Clinical spasms were determined by vEEG for at least 24 hours at Day 10 and Day 20. The number of participants with spasm-free duration have been presented.
Number of Participants With Seizure-free Days
Seizure-free days were measured using data obtained from participants' daily dairy. Participants without seizures have been reported.
Number of Responders
A responder is defined as a participant experiencing a greater than equal to (>=) 50 percent (%) decrease in spasm frequency. Test for responders was conducted by vEEG for up to 24 hours at Day 10 and Day 20
Developmental Assessment Using Denver-II Developmental Test at Day 20
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00441896
Brief Title
A Randomized, Controlled Trial of Ganaxolone in Patients With Infantile Spasms
Official Title
A Double-blind, Placebo-controlled, Dose-ranging Clinical Study to Evaluate the Safety, Tolerability, and Antiepileptic Activity of Ganaxolone in Treatment of Patients With Infantile Spasms
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Completed
Study Start Date
January 2007 (undefined)
Primary Completion Date
May 2008 (Actual)
Study Completion Date
May 2008 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Marinus Pharmaceuticals
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The study consists of cohorts where participants are randomized, in a 2:1 ratio, to 1 of 2 sequences, A and B. In each cohort, Sequence A, comprised of participants, who will receive ascending doses of ganaxolone and ascending doses of placebo. Sequence B, comprised of participants, who will receive ascending doses of placebo and ascending doses of ganaxolone. The dosing level in each subsequent cohort will be based upon experience gained from previous cohorts.
Detailed Description
Male or female, 4 to 24 months of age (inclusive) with a diagnosis of IS with a 24 hour video EEG (vEEG) recording confirming the diagnosis and previously treated with 3 or fewer antiepileptic drugs (AEDs) are eligible for the study. The subject is able to continue treatment with concomitant AEDs (no more than 2; adrenocorticotropic hormone [ACTH], corticosteroids, felbamate, and vigabatrin are not allowed concomitantly). A ketogenic diet is permitted if it can be maintained for the duration of the study.
There will be a total of three weekly 24-hr video EEGs (baseline, end of weeks 1 and 2 of treatment). Dosing titration begins the day after each video EEG during the inpatient stay. All subjects will be receiving ganaxolone the day after the second video EEG.
A Data Monitoring Board (DMB) will determine whether successive cohorts of subjects can be dosed at an increased dose level; up to a maximum of 6 cohorts.
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
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
57 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ganaxolone
Arm Type
Experimental
Arm Description
ganaxolone
Arm Title
non-active drug
Arm Type
Placebo Comparator
Arm Description
placebo
Intervention Type
Drug
Intervention Name(s)
Ganaxolone
Intervention Type
Other
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Change From Baseline in Frequency of Spasm Clusters at Day 10
Description
Spasm clusters were determined by a 24-hour video-electroencephalography (vEEG) at Day 10. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Baseline was defined as the Day 0 assessment before study drug infusion.
Time Frame
Baseline (Day 0) and Day 10
Secondary Outcome Measure Information:
Title
Change From Baseline in Frequency of Spasm Clusters at Day 20
Description
Spasm clusters were determined by a 24-hour vEEG at Day 20. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Baseline was defined as the Day 0 assessment before study drug infusion.
Time Frame
Baseline (Day 0) and Day 20
Title
Number of Participants With Absence of Hypsarrhythmia
Description
Absence of hypsarrhythmia was determined by 24-hour vEEG at Day 10 and Day 20.
Time Frame
Day 10 and Day 20
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
Baseline (Day 0), Day 10 and Day 20
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
Baseline (Day 0), Day10 and Day 20
Title
Number of Participants With Spasm-free Durations
Description
Clinical spasms were determined by vEEG for at least 24 hours at Day 10 and Day 20. The number of participants with spasm-free duration have been presented.
Time Frame
Day 10 and Day 20
Title
Number of Participants With Seizure-free Days
Description
Seizure-free days were measured using data obtained from participants' daily dairy. Participants without seizures have been reported.
Time Frame
From Day 8 to Day 10 and From Day 18 to Day 20
Title
Number of Responders
Description
A responder is defined as a participant experiencing a greater than equal to (>=) 50 percent (%) decrease in spasm frequency. Test for responders was conducted by vEEG for up to 24 hours at Day 10 and Day 20
Time Frame
Day 10 and Day 20
Title
Developmental Assessment Using Denver-II Developmental Test at Day 20
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
At Day 20
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:
Be diagnosed with IS (regardless of etiology- except for a progressive neurologic illness). 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 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 or fewer AEDs.
If being treated with concomitant AEDs
Current AEDs have been at a constant daily dose for at least 2 weeks; Note: Subjects with minor dose adjustments may be allowed to enter the study after shorter periods after detailed discussion with the medical monitor.
Have a stable clinical response/plateau for at least 2 weeks
Are able to continue treatment with no more than 2 concomitant AEDs (ACTH, corticosteroids, felbamate, and vigabatrin are not allowed concomitantly).
A ketogenic diet is permitted if it can be maintained for the duration of the study.
Be a male or female, 4 to 24 months of age (inclusive)
Have a Parent/Guardian who is properly informed of the nature and risks of the clinical study, who is willing and capable of complying with all clinical study procedures, and has given informed consent in writing prior to entering the clinical study
Be able to participate for the full term of the clinical study.
Exclusion Criteria:
Treatment with corticosteroids, ACTH, vigabatrin, felbamate, or any AED not approved by Regulatory Agencies, 2 weeks prior to randomization.
Treatment with more than two AEDs at baseline.
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 imaging (MRI).
Have any disease or condition (medical or surgical) at screening that might compromise the hematologic, cardiovascular, pulmonary, renal, gastrointestinal, 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 aminotransferase (AST), alanine aminotransferase (ALT), or total bilirubin greater than four times the upper limit of normal (ULN) or 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 randomization.
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 Care Center of Northwest Florida
City
Pensacola
State/Province
Florida
ZIP/Postal Code
32504
Country
United States
Facility Name
Child Neurology Center of Northwest Florida
City
Pensacola
State/Province
Florida
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 System
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
Links:
URL
https://marinuspharma.com/
Description
information about ganaxolone
Learn more about this trial
A Randomized, Controlled Trial of Ganaxolone in Patients With Infantile Spasms
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