Arbaclofen vs. Placebo in the Treatment of Children and Adolescents With ASD (ARBA)

Study Overview
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Brief Summary
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This study will examine the safety and efficacy of arbaclofen vs. placebo on social function in children and adolescents with Autism Spectrum Disorder (ASD).

Detailed Description
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There are no pharmacologic treatments available for social function deficits in individuals with ASD. The data for pharmacologic treatment of repetitive behaviours in this disorder has also become difficult to interpret given that the last two large multisite trials of selective serotonin reuptake inhibitors (SSRIs) in autism are reported to be negative for the treatment of repetitive behaviours. Only the associated symptom of irritability has 2 drugs with Food and Drug Administration (FDA) indications, whereas no systematic data exists on the pharmacologic treatment of anxiety in ASD, and response to rates to stimulants for hyperactivity are lower than what is seen in Attention Deficit Hyperactivity Disorder (ADHD). In addition, there are no biological markers of treatment response identified in this population at this point. This study will examine the potential efficacy and safety of arbaclofen for social function, and will explore biological markers of safety and treatment response.

Official Title
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A Randomized Placebo-controlled Trial of ARBaclofen vs. Placebo in the Treatment of Children and Adolescents With ASD

Conditions
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Autism Spectrum Disorder

Intervention / Treatment
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* Drug: Arbaclofen
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Outpatients 5-17 years of age inclusive. Meet Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). DSM-5 criteria will be established by a clinician with expertise with individuals with ASD. Diagnosis will be supported by the Autism Diagnostic Observation Schedule, Second Edition (ADOS-2). Complex language to qualify for ADOS-2 modules 3 or 4. If already receiving stable concomitant medications affecting behaviour, have stable regimens with no changes during the preceding 6 weeks prior to Screening, and will not electively initiate new or modify ongoing medications for the duration of the study. If already receiving stable non-pharmacological educational and behavioural interventions, have continuous participation during the preceding 3 months prior to Screening, and will not electively initiate new or modify ongoing interventions for the duration of the study. Have normal physical examination and laboratory test results at Screening. If abnormal, the finding(s) must be deemed clinically insignificant by the Investigator. Ability to obtain written informed consent from the participant, if developmentally appropriate. If a participant does not have the capacity to consent, ability to obtain assent (if developmentally appropriate), as well as written informed consent from their parent(s)/legal guardian(s). Exclusion Criteria: Pregnant females; sexually active females on inadequate birth control. Have a serious medical condition that, based on Investigator judgment, might interfere with the conduct of the study, confound interpretation of the study results, or endanger their own well-being. Have evidence of any significant hematological, endocrine, cardiovascular (including uncorrected symptomatic congenital heart disease), respiratory, renal, hepatic, or gastrointestinal disease, not including mild common pediatric diseases in these areas that are stable (e.g. mild asthma, constipation, etc.). Have unstable epilepsy (i.e. seizures occurring within the last 6 months), or have epilepsy and not on stable doses of antiepileptic medications (i.e. dose changes within the last 3 months). Have a history of drug abuse. Have hypersensitivity to arbaclofen or any components of its formulation. Unable to tolerate venipuncture procedures for blood sampling. Actively enrolled in another intervention study. Taking racemic bacblofen, vigabatrin, tiagapine, riluzole, clobazam or regular benzodiazepine use (prn and hs use is allowed). Unable to take oral medications. Known hypersensitivity to racemic baclofen. Inability to speak and understand English sufficiently enough to allow for the completion of all study assessments (parent/legal guardian; participant).

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arbaclofen<br> | Drug: Arbaclofen<br>* Administered orally as disintegrating tabs, round, white and beveled edges, at the following strengths: 5mg, 10mg, 15mg and 20mg<br>|
| Placebo Comparator: Placebo<br> | Other: Placebo<br>* Administered orally as disintegrating tabs, round, white and beveled edges<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) - Social Domain | To examine the effect of arbaclofen vs. placebo social function | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Global Impressions - Impression Scale - Improvement (CGI-I) | To examine the effect of arbaclofen vs. placebo on measures of global function | 16 weeks | 
| Aberrant Behavior Checklist (ABC) - Social Withdrawal Subscale | To examine the effect of arbaclofen vs. placebo on social withdrawal | 16 weeks | 
| Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) - Communication Domain | To examine the effect of arbaclofen vs. placebo on communication | 16 weeks | 
| Safety Monitoring Uniform Report Form (SMURF) | To examine the safety and tolerability of arbaclofen in children and adolescents with ASD | 16 weeks | 
| Clinical Global Impressions - Impression Scale - Global (CGI-I-Global) | To examine the safety and tolerability of arbaclofen in children and adolescents with ASD | 16 weeks | 
| Epworth Sleepiness Scale for Children and Adolescents (ESS-CHAD) | To examine the safety and tolerability of arbaclofen in children and adolescents with ASD | 16 weeks | 
| Suicidality assessment using the Columbia-Suicide Severity Rating Scale (C-SSRS) | To examine the safety and tolerability of arbaclofen in children and adolescents with ASD | 16 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ASD, Autism