Ganaxolone Treatment in Children With Fragile X Syndrome

Sponsor

Marinus Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT01725152

Collaborator

University of California, Davis (Other), U.S. Army Medical Research and Development Command (U.S. Fed)

Enrollment

Locations

Arms

Duration (Months)

29.5

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This Phase 2 proof-of-concept study is a double-blind, randomized, placebo-controlled, crossover study to investigate ganaxolone treatment in children with fragile x syndrome (FXS). Up to 60 subjects (ages 6-17 yrs) will be randomized to receive either ganaxolone or placebo for 6 weeks and then cross over to the opposite treatment for another 6 weeks. The aim of the study is assess the safety, tolerability and efficacy of ganaxolone for treatment of anxiety and attention in subjects with FXS. The hypothesis is that ganaxolone treatment compared to placebo will improve anxiety and attention as measured by the several neuropsychological and psychometric tests.

Condition or Disease	Intervention/Treatment	Phase
Fragile x Syndrome	Drug: Ganaxolone Drug: Placebo	Phase 2

Detailed Description

This is a single center study at UC Davis MIND Institute. Children with fragile x syndrome between the ages of 6-17yrs, inclusive will be randomized at a 1:1 ratio to receive ganaxolone or placebo treatment for 6 weeks, discontinue treatment and washout for 2 weeks, and then cross over to the opposite treatment for another 6 weeks. The primary aim of the study is to assess efficacy of ganaxolone treatment compared to placebo on clinical behaviors such as anxiety and attention as measured by Clinician's Global Impression-Improvement (CGI-I). The key secondary efficacy measure is the Pediatric Anxiety Scale (PARS). Other secondary efficacy measures include the visual analog scale (VAS), Anxiety, Depression, Attention, and Mood Scale (ADAMS), Swanson, Nolan, and Pelham-IV Questionnaire (SNAP-IV), and Aberrant Behavior Checklist- Community Edition (ABC-C). Tolerability and safety will be monitored by routine vital signs, physical/neurological exams, ECGs, clinical laboratory and adverse event assessments.

Study Design

Study Type:

Interventional

Actual Enrollment :

59 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Controlled, Double-blind, Crossover Trial of Ganaxolone in Children With Fragile X Syndrome

Study Start Date :

Nov 1, 2012

Actual Primary Completion Date :

Oct 16, 2015

Actual Study Completion Date :

Nov 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ganaxolone 3 mg/kg up to 12 mg/kg, with maximum of 1500 mg/day	Drug: Ganaxolone oral suspension, given in 3 divided doses Other Names: GNX GNX OS
Placebo Comparator: Placebo non active	Drug: Placebo oral suspension, given in 3 divided doses Other Names: PBO

Arm

Intervention/Treatment

Experimental: Ganaxolone

3 mg/kg up to 12 mg/kg, with maximum of 1500 mg/day

Drug: Ganaxolone

oral suspension, given in 3 divided doses

Other Names:

GNX

GNX OS

Placebo Comparator: Placebo

non active

Drug: Placebo

oral suspension, given in 3 divided doses

Other Names:

PBO

Outcome Measures

Primary Outcome Measures

Clinician's Global Impression-Improvement (CGI-I) [Weeks 3, 6, 8, 11, 14]

Secondary Outcome Measures

Pediatric Anxiety Rating Scale (PARS) [Baseline, Weeks 3, 6, 8, 11, 14]
Visual Analog Scale [Baseline, Weeks 6, 8, 14]
Anxiety, Depression, and Mood Scale (ADAMS) [Baseline, Weeks 6, 8, 14]
Aberrant Behavior Checklist [Baseline, Weeks 6, 8, 14]
Swanson, Nolan, and Pelham-IV Questionnaire (SNAP-IV) [Baseline, Weeks 6, 8, 14]

Other Outcome Measures

KiTAP- Test of Attentional Performance for Children [Baseline, Weeks 6, 8, 14]
Prepulse Inhibition (PPI) [Baseline, Weeks 6, 8, 14]
Social Gaze (eye tracking) [Baseline, Weeks 6, 8, 14]
Event-related brain potentials (ERP) [Baseline, Weeks 6, 8, 14]

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Years to 17 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

molecular documentation of FMR1 full mutation
ages 6-17 yrs, inclusive
sexually active subjects are required to use a medically acceptable form of birth control

Exclusion Criteria:

non-English or Spanish speaking subjects
concomitant systemic steroid, vigabatrin, felbamate and ketoconazole
changes in medications within last 2 months
clinically unstable medical disease, progressive CNS disease/disorder
history of recurrent status epilepticus
unwilling to withhold grapefruit or grapefruit juice for the duration of the study
actively suicidal

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	M.I.N.D. Institute at University of California at Davis Medical Center	Sacramento	California	United States	95817
2	Antwerp University Hospital	Edegem		Belgium	2650

Sponsors and Collaborators

Marinus Pharmaceuticals
University of California, Davis
U.S. Army Medical Research and Development Command

Investigators

Principal Investigator: Randi J Hagerman, MD, M.I.N.D. Institute at University of California at Davis Medical Center
Principal Investigator: Berten Ceulemans, M.D.; Ph. D., University Hospital, Antwerp