Ganaxolone Treatment in Children With Fragile X Syndrome

NCT01725152 | Completed Phase 2 Results DMC

• 1 other identifier: 1042-0800
• Study Type: interventional
• Target: 59
• Locations: 2 countries
• Sites: 2

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). The objective of the study is to assess the safety, tolerability and efficacy of ganaxolone in the treatment of anxiety and attention in subjects with FXS.

Conditions

Fragile x Syndrome

Keywords

fragile x syndrome; ganaxolone; anxiety; attention; pediatric

Outcome Measures

Primary Outcomes (1)

• Clinical Global Impression-Improvement (CGI-I) Scale

  The CGI-I scale is a clinician-rated 7-point scale used to assess how much the participant's illness had improved or worsened relative to a Baseline state at the beginning of the intervention. It was rated as: 1. "very much improved"; 2. "much improved"; 3. "minimally improved"; 4. "no change"; 5. "minimally worse"; 6. "much worse"; 7. "very much worse". Higher scores indicated worse condition.

  Week 14 (End of Treatment)

Secondary Outcomes (5)

• Pediatric Anxiety Rating Scale (PARS) Total Score

  Week 14 (End of Treatment)

• Visual Analogue Scale (VAS)

  Week 14 (End of Treatment)

• Anxiety, Depression, and Mood Scale (ADAMS)

  Week 14 (End of Treatment)

• Aberrant Behavior Checklist (ABC)

  Week 14 (End of Treatment)

• Swanson, Nolan, and Pelham-IV Questionnaire (SNAP-IV)

  Week 14 (End of Treatment)

Study Arms (2)

Ganaxolone then Placebo

EXPERIMENTAL

Participants first received ganaxolone. They were first titrated up to the 12 milligram per kilogram (mg/kg) three times daily (tid) during a 2-week titration phase, then maintained on that dose for an additional 4 weeks. After a washout period of 2 weeks, participants received placebo for a duration of 6 weeks (from week 8 to 14).

Drug: Ganaxolone; Drug: Placebo

Placebo then Ganaxolone

EXPERIMENTAL

Participants first received placebo. They were first titrated up to the 12 mg/kg tid during a 2-week titration phase, then maintained on that dose for an additional 4 weeks. After a washout period of 2 weeks, participants received ganaxolone for a duration of 6 weeks (from week 8 to 14).

Drug: Ganaxolone; Drug: Placebo

Interventions

Ganaxolone DRUG

oral suspension, given in 3 divided doses

Ganaxolone then Placebo; Placebo then Ganaxolone

Placebo DRUG

oral suspension, given in 3 divided doses

Ganaxolone then Placebo; Placebo then Ganaxolone

Eligibility Criteria

• Age: 6 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (2)

M.I.N.D. Institute at University of California at Davis Medical Center

Sacramento, California, 95817, United States

Location

Antwerp University Hospital

Edegem, 2650, Belgium

Location

Related Publications (1)

• Ligsay A, Van Dijck A, Nguyen DV, Lozano R, Chen Y, Bickel ES, Hessl D, Schneider A, Angkustsiri K, Tassone F, Ceulemans B, Kooy RF, Hagerman RJ. A randomized double-blind, placebo-controlled trial of ganaxolone in children and adolescents with fragile X syndrome. J Neurodev Disord. 2017 Aug 2;9(1):26. doi: 10.1186/s11689-017-9207-8.

  PMID: 28764646 DERIVED

MeSH Terms

Conditions

Fragile X Syndrome; Anxiety Disorders

Interventions

ganaxolone

Condition Hierarchy (Ancestors)

X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Sex Chromosome Disorders; Chromosome Disorders; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Heredodegenerative Disorders, Nervous System; Mental Disorders

Results Point of Contact

• Title: Marinus
• Organization: Marinus Pharmaceuticals, Inc.

clinicaltrials@marinuspharma.com

484-801-4670

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 7, 2012
• First Posted: November 12, 2012
• Study Start: November 1, 2012
• Primary Completion: October 16, 2015
• Study Completion: November 1, 2016
• Last Updated: April 10, 2023
• Results First Posted: April 10, 2023

Record last verified: 2023-03

Locations

US (1); BE (1)