Clinical Trial Evaluating the Effects of Ganaxolone in Children With Autism

A Randomized Controlled Trial of Ganaxolone for Children With Autism Spectrum Disorder

The goal of this study is to conduct a randomized, placebo-controlled trial (RCT) of ganaxolone, a neuroactive steroid (NAS), in autistic children and adolescents aged 5 to 17 years old. Ganaxolone is approved and effective for treating seizures in children as young as 2 years old who have CDKL5 deficiency disorder (CDD), a neurogenetic condition associated with developmental delays, seizure disorder, hypotonia, visual impairments, and autistic features. The primary outcome of interest for this trial is irritability on the Aberrant Behavior Checklist (ABC) because it is a common symptom of emotion dysregulation in ASD that impacts quality of life, including mental health, independence, educational opportunities, and integration into the community. The secondary domains of interest for this trial are restricted and repetitive behaviors (RRB), specifically insistence on sameness (IS), a subdomain of RRB characterized by inflexibility and a strong preference for predictable routines and familiar environments. Secondary outcome measures include the IS subscale from the Dimensional Assessment of Repetitive Behaviors (DARB) and subscales of the Clinical Global Impressions Scale for irritability (CGI-IR) and IS (CGI-IS). For participants living within 150 miles of Stanford University, we require participants to attend site visits and attempt EEG and MRI procedures before and after the trial, though we are recruiting nationally and the study can be completed without site vists.

Study Overview

• Status: Not yet recruiting
• Conditions: Autism Spectrum Disorder; Autism in Children; Autistic Disorder in Children and Adolescents
• Intervention / Treatment: Drug: Ganaxolone (Ztalmy); Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 66
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Robin Libove, BS; Phone Number: (650) 736-1235; Email: autismdd@stanford.edu
• Study Contact Backup: Name: Briana Hernandez, BS; Phone Number: (650) 736-1235; Email: autismdd@stanford.edu

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University
      • Contact: Robin Libove, BS; Phone Number: (650) 736-1235; Email: autismdd@stanford.edu
      • Contact: Briana Hernandez, BS; Phone Number: (650) 736-1235; Email: autismdd@stanford.edu
      • Principal Investigator: Antonio Hardan, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. children between the ages of 5 years and 17 years old at enrollment
2. diagnosis of autism spectrum disorder based on DSM-5 criteria and confirmed with the Autism Diagnostic Inventory - Revised (ADI-R) and Autism Diagnostic Observation Schedule 2nd edition (ADOS-2), or Childhood Autism Rating Scales (CARS)
3. medical stability based on clinical interview
4. stable medication regimens (2 weeks, with the exception of fluoxetine for 4 weeks)
5. stable psychosocial therapies (4 weeks) prior to randomization and no plans to change treatments or intensity during the trial
6. high rates of irritability defined as the Aberrant Behavior Checklist irritability subscale score > 18
7. for participants who are sexually active, use of an effective contraceptive (e.g., birth control medications for female participants and condoms for male participants) and no plans for pregnancy throughout the trial
8. for females, negative urine pregnancy test at baseline
9. no planned changes in school placement
10. for participants living within 150 miles of Stanford University, have the ability to attend site visits and attempt EEG and MRI procedures before and after the trial
11. availability of a reliable informant who interacts with the participant regularly and can reliably complete assessments in English regarding their behaviors throughout the trial
12. ability to participate in the testing administered in English to the extent that valid standard scores and biological samples can be obtained.

Exclusion Criteria:

1. any unstable medical condition, such as unstable seizure disorder or heart disease
2. any lifetime diagnosis of severe psychiatric (e.g., schizophrenia) or neurodegenerative conditions
3. concomitant use of any neuroactive steroids or corticosteroids.
4. history of substance abuse or active/planned use of alcohol, opioids, or cannabinoids
5. recent history or current suicidal ideation assessed with the Columbia-Suicide Severity Rating Scale (C-SSRS) and by clinical interview with the study physician
6. pregnancy and mothers who are breastfeeding
7. prior participation in any clinical trial in the 30 days prior to study entry
8. known intolerance or hypersensitivity to ganaxolone or similar analogs
9. Concomitant use of medications that are inducers of CYP450 3A4/5, such as rifampin, carbamazepine, phenytoin, phenobarbital, and St. John's wort

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Ganaxolone Arm; Participants receives up to 20 weeks of Ganaxolone treatment	Drug: Ganaxolone (Ztalmy); Liquid oral suspension of ganaxolone will be administered orally with food three times daily. Dosage will be increased based on tolerability, no more frequently than every 7 days. Dosing will be flexible and occur between 4 to 8 weeks, depending on tolerability and response across each individual patient. Once the maximum tolerated dose is identified, it will be held stable for the remaining 4-8 weeks of the study, for a total of 12 weeks in the randomized, controlled phase. The titration schedule for patients weighing 28 kg or less is: Days 1-7: 2 mg/kg x 3 per day Days 8-14: 4 mg/kg x 3 per day Days 15-21: 8 mg/kg x 3 per day Days 22-28: 14 mg/kg x 3 per day Day 29 and thereafter: 21 mg/kg x 3 per day The titration schedule for patients weighing more than 28 kg is: Days 1-7: 50 mg/kg x 3 per day Days 8-14: 100 mg/kg x 3 per day Days 15-21: 200 mg/kg x 3 per day Days 22-28: 400 mg/kg x 3 per day Day 29 and thereafter: 600 mg/kg x 3 per day
Placebo Comparator: Placebo Arm; Participants receives up to 20 weeks of placebo treatment	Drug: Placebo; The placebo suspension will contain the same components as the active compound, except for ganaxolone.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The score on irritability subscale on the Aberrant Behavior Checklist (ABC)	It is a common symptom of emotion dysregulation in ASD that impacts quality of life, including mental health, independence, educational opportunities, and integration into the community, and ganaxolone may provide more direct benefits or increased tolerability compared to atypical antipsychotics.	The measures will be completed at screening, baseline, week 2, week 4, week 6, week 8, week 10, week 12, week 14, and week 16.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The score of Insistence on Sameness subscale of the Dimensional Assessment of Repetitive Behaviors (DARB)	The DARB is an informant report measure developed and validated following methods outlined by the NIH Patient-Reported Outcome Measurement Information System (PROMIS) framework. Comprehensive, multi-trait, multi-method factor analyses across existing RRB instruments and meta-analysis of factor analyses identified the following eight RRB subdomains: repetitive motor behaviors, insistence on sameness, restricted interests, unusual interests, self-injurious behaviors, sensory sensitivity, obsessions and compulsions, and repetitive language.	The measures will be completed at screening, baseline, week 2, week 4, week 6, week 8, week 10, week 12, week 14, and week 16.
The score on irritability subscale on the Clinical Global Impressions Scale (CGI-IR)	The study physician will also administer the CGI scale, which includes clinical judgment of the severity of illness and global improvement. The CGI is widely used in psychopharmacological studies and has high sensitivity to measure medication effects.	The measures will be completed at screening, baseline, week 2, week 4, week 6, week 8, week 10, week 12, week 14, and week 16.
The score on Insistence on Sameness subscale on the Clinical Global Impressions Scale(CGI-IS)	The study physician will also administer the CGI scale, which includes clinical judgment of the severity of illness and global improvement. The CGI is widely used in psychopharmacological studies and has high sensitivity to measure medication effects.	These measures will be completed at screening, baseline, week 2, week 4, week 6, week 8, week 10, week 12, week 14, and week 16.

Collaborators and Investigators

• Sponsor: Stanford University
• Collaborators: SPARK NS
• Investigators: Principal Investigator: Antonio Y. Hardan, M.D., Stanford University School of Medicine-Psychiatry and Behavioral Sciences - Child and Adolescent Psychiatry and Child Development

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2027
• Primary Completion (Estimated): January 1, 2030
• Study Completion (Estimated): January 1, 2030

Study Registration Dates

• First Submitted: June 3, 2026
• First Submitted That Met QC Criteria: June 3, 2026
• First Posted (Actual): June 9, 2026

Study Record Updates

• Last Update Posted (Actual): June 9, 2026
• Last Update Submitted That Met QC Criteria: June 3, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Autism; Irritability; GABA; Ganaxolone; Autism disorder in children and adolescents; Ztalmy; Insistance on Sameness; Emotional Regulation Difficulties
• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Autism Spectrum Disorder; Autistic Disorder; ganaxolone
• Other Study ID Numbers: IRB-84478

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No