A Randomized, Controlled Trial of Ganaxolone in Patients With Infantile Spasms

NCT ID: NCT00441896

Last Updated: 2023-06-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 57 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-01-31
• Study Completion Date: 2008-05-31

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.

Conditions

Infantile Spasms

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

ganaxolone

ganaxolone

Group Type: EXPERIMENTAL

Ganaxolone

Intervention Type: DRUG

non-active drug

placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Interventions

Ganaxolone

Intervention Type: DRUG

Placebo

Intervention Type: OTHER

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.

• Minimum Eligible Age: 4 Months
• Maximum Eligible Age: 24 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Marinus Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Children's Hospital of Los Angeles

Los Angeles, California, United States

Mattel Children's Hospital at UCLA

Los Angeles, California, United States

Children's National Medical Center

Washington D.C., District of Columbia, United States

Miami Children's Hospital, The Brain Institute

Miami, Florida, United States

Child Neurology Care Center of Northwest Florida

Pensacola, Florida, United States

Child Neurology Center of Northwest Florida

Pensacola, Florida, United States

University of Chicago Comer Children's Hospital

Chicago, Illinois, United States

Minnesota Epilepsy Group, P.A.

Saint Paul, Minnesota, United States

Montefiore Medical Center- Albert Einstein College of Medicine

The Bronx, New York, United States

Le Bonheur Children's Medical Center

Memphis, Tennessee, United States

Dallas Pediatric Neurology Associates

Dallas, Texas, United States

Texas Children's Hospital

Houston, Texas, United States

Virginia Commonwealth University Health System

Richmond, Virginia, United States

Children's Hospital and Regional Medical Center

Seattle, Washington, United States

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, United States

Countries

United States

Related Links

https://marinuspharma.com/

information about ganaxolone

Other Identifiers

1042-0500

Identifier Type: -

Identifier Source: org_study_id