Infantile SpasmsPhase 2NCT00441896
A Randomized, Controlled Trial of Ganaxolone in Patients With Infantile Spasms
A Phase 2 study testing Ganaxolone in people with Infantile Spasms, run by Marinus Pharmaceuticals at 15 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 4 to 24 months
- Conditions the study is for
- Infantile Spasms
- What is being tested?
- Ganaxolone
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 57 participants
- Where
- 15 sitesUnited States
- Study dates
- Jan 2007to May 2008
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 to 24 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
Trial locations and contacts
15 sites in 1 country.
15 sites in 1 country
United States15 sites
University of Chicago Comer Children's Hospital
Chicago, Illinois, 60637
Dallas Pediatric Neurology Associates
Dallas, Texas, 75230
Texas Children's Hospital
Houston, Texas, 77030
Children's Hospital of Los Angeles
Los Angeles, California, 90027
Mattel Children's Hospital at UCLA
Los Angeles, California, 90095
Le Bonheur Children's Medical Center
Memphis, Tennessee, 38105
Miami Children's Hospital, The Brain Institute
Miami, Florida, 33155
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53201
Child Neurology Care Center of Northwest Florida
Pensacola, Florida, 32504
Child Neurology Center of Northwest Florida
Pensacola, Florida
Virginia Commonwealth University Health System
Richmond, Virginia, 23298
Minnesota Epilepsy Group, P.A.
Saint Paul, Minnesota, 55102
Children's Hospital and Regional Medical Center
Seattle, Washington, 98105
Montefiore Medical Center- Albert Einstein College of Medicine
The Bronx, New York, 10467
Children's National Medical Center
Washington D.C., District of Columbia, 20010
About this study
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
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.
Read the 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.
- Conditions
- Infantile Spasms
- Being tested
- Ganaxolone, Placebo
- Keywords
- infantile spasms, anticonvulsant, pediatric epilepsy, West Syndrome, epileptic spasms
- Medical subject headings
- Spasms, Infantile
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GanaxoloneDrug
PlaceboOther
| Study group | Role | What they receive |
|---|---|---|
| ganaxolone | Experimental | ganaxolone Receives: Drug: Ganaxolone |
| non-active drug | Placebo comparator | placebo Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline (Day 0) and Day 10
Secondary outcomes (8)
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.
Measured: Baseline (Day 0) and Day 20
Number of Participants With Absence of Hypsarrhythmia
Absence of hypsarrhythmia was determined by 24-hour vEEG at Day 10 and Day 20.
Measured: 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.
Measured: Baseline (Day 0), Day 10 and Day 20
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.
Measured: Baseline (Day 0), Day10 and Day 20
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.
Measured: Day 10 and Day 20
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.
Measured: From Day 8 to Day 10 and From Day 18 to Day 20
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
Measured: 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.
Measured: At Day 20
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Mar 2007 (estimated)
- Study startJan 2007
- Primary completionMay 2008
- Study completionMay 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Infantile SpasmsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 57 participants (actual)
Sponsor and investigators
- Lead sponsor
- Marinus Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00441896
- Sponsor's protocol ID
- 1042-0500
- Status last verified
- May 2023
- First submitted
- 27 Feb 2007
- Last updated
- 2 Jun 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 2 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00441896
- Acronym / sponsor ID
- 1042-0500
- Conditions
- Infantile Spasms
- Keywords
- infantile spasms, anticonvulsant, pediatric epilepsy, West Syndrome, epileptic spasms
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 57 participants (actual)
- Lead sponsor
- Marinus PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Jan 2007
- Primary completion
- May 2008 (actual)
- Study completion
- May 2008 (actual)
- First posted
- 1 Mar 2007 (estimated)
- Results
- Posted 2 Jun 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ganaxolone | Experimental | Drug: Ganaxoloneganaxolone |
| non-active drug | Placebo comparator | Other: Placeboplacebo |
Who may qualify
- Ages
- 4 to 24 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (12 listed)
- 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
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ganaxolone | Drug | ganaxolone |
| Placebo | Other | non-active drug |
Primary outcome
Change From Baseline in Frequency of Spasm Clusters at Day 10
Time frame: Baseline (Day 0) and 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.
8 secondary outcomes
Change From Baseline in Frequency of Spasm Clusters at Day 20
Time frame: Baseline (Day 0) and Day 20
Number of Participants With Absence of Hypsarrhythmia
Time frame: Day 10 and Day 20
Number of Participants With Change in Clinical Status on the Investigator's Global Assessment
Time frame: Baseline (Day 0), Day 10 and Day 20
Number of Participants With Change in Clinical Status on Caregiver's Global Assessment
Time frame: Baseline (Day 0), Day10 and Day 20
Number of Participants With Spasm-free Durations
Time frame: Day 10 and Day 20
Number of Participants With Seizure-free Days
Time frame: From Day 8 to Day 10 and From Day 18 to Day 20
Number of Responders
Time frame: Day 10 and Day 20
Developmental Assessment Using Denver-II Developmental Test at Day 20
Time frame: At Day 20
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jun 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- information about ganaxoloneLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
15 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ganaxolone in people with Infantile Spasms, run by Marinus Pharmaceuticals at 15 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Jun 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in Frequency of Spasm Clusters at Day 10 (time frame: Baseline (Day 0) and Day 10). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jun 2023.