Trial to Investigate the Safety and Efficacy of Cannabidiol Oral Solution (GWP42003-P; CBD-OS) in Children and Adolescents With Autism Spectrum Disorder

Study Overview
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Brief Summary
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This study will be conducted to evaluate the efficacy of GWP42003-P, compared with placebo, in reducing symptom severity in children with Autism Spectrum Disorder (ASD).

Official Title
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An Exploratory, Phase 2, Randomized, Double-blind, Placebo-controlled Trial to Investigate the Safety and Efficacy of Cannabidiol Oral Solution (GWP42003-P; CBD-OS) in Children and Adolescents With Autism Spectrum Disorder

Conditions
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Autism Spectrum Disorder

Intervention / Treatment
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* Drug: GWP42003-P
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant weight is at least 12 kilograms (kg). Participants (if possessing adequate understanding, in the investigator's opinion) and their parent(s)/legal representative are willing and able to give informed assent and consent for participation in the trial. Participant and their caregiver are willing and able (in the investigator's opinion) to comply with all trial requirements. Participant has a diagnosis of Autism Spectrum Disorder (ASD) as per Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for ASD, confirmed by Autism Diagnostic Observational Schedule (ADOS-2) criteria (conducted within 2 years at the trial site or at screening by a qualified assessor). Note: During special circumstances (e.g., COVID-19 pandemic) where the ADOS-2 cannot be performed due to site restrictions (e.g., mandatory use of face masks) and an ADOS- 2 conducted within 2 years at the trial site by a qualified assessor is not available, eligibility can be confirmed using: 1) an ADOS-2 performed within 2 years by a qualified assessor (external to the site); 2) if 1) is not available, eligibility may be confirmed using the Autism Diagnostic Interview, Revised (ADI-R) at screening. Clinical Global Impressions - Improvement Scale (CGI-S) ≥ 4 (moderately ill) at screening and randomization. Intelligence quotient (IQ) ≥ 70 at screening, or measured within 1 year of screening, using Wechsler Abbreviated Scale of Intelligence Scale Second Edition (WASI-II). All medications or interventions (including psychosocial interventions, dietary supplements, probiotics, speech therapy, etc.) for ASD related symptoms must have been stable for 4 weeks prior to screening and randomization, and the patient/caregiver should be willing to maintain a stable regimen throughout the trial. Participants must have the ability to swallow the investigational medicinal product (IMP), provided as a liquid solution. Participant and/or parent(s)/legal representative is willing to allow the responsible authorities to be notified of participation in the trial, if mandated by local law. Participant and/or parent(s)/legal representative is/are willing to allow the participant's primary care practitioner (if they have one) and consultant (if they have one) to be notified of participation in the trial if the primary care practitioner/consultant is different from the investigator. Exclusion Criteria: Current diagnosis of bipolar disorder, psychosis, schizophrenia, schizoaffective disorder, or major depression (participants with depression in remission may be included) Has a diagnosis other than ASD that dominates the clinical presentation (e.g., Attention Deficit Hyperactivity Disorder [ADHD]) Has a progressive neurological condition Seizures in the past 24 weeks Changes in anticonvulsive therapy within the last 12 weeks Currently taking more than 2 anti-epileptic drugs (AEDs) Taking sirolimus, everolimus, temsirolimus, or tacrolimus Taking clobazam Taking omeprazole, lansoprazole, tolbutamide, or warfarin Taking repaglinide, pioglitazone, rosiglitazone, montelukast, bupropion, or efavirenz Currently using or has used recreational or medicinal cannabis, cannabinoid-based medications (including Sativex®, or Epidiolex®) within the 12 weeks prior to screening and is unwilling to abstain for the duration of the trial Participant has any known or suspected hypersensitivity to cannabinoids or any of the excipients of the IMP, such as sesame oil. Participant has moderately impaired hepatic function at screening, defined as serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2 × upper limit of normal (ULN) or total bilirubin (TBL) > 2 × ULN. This criterion can only be confirmed once the laboratory results are available; participants enrolled into the trial who are later found to meet this criterion must be screen-failed. Participant is male and fertile (i.e., after puberty unless permanently sterile by bilateral orchidectomy) unless willing to ensure that they use male contraception (condom) or remain sexually abstinent during the trial and for 12 weeks thereafter. Participant is female and of childbearing potential (i.e., following menarche and until becoming postmenopausal for ≥ 12 consecutive months unless permanently sterile by hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) unless willing to ensure that they use a highly effective method of birth control (e.g., hormonal contraception, intrauterine device/hormone-releasing system, bilateral tubal occlusion, vasectomized partner, sexual abstinence) during the trial and for 12 weeks thereafter. Female participant who is pregnant (positive pregnancy test), lactating or planning pregnancy during the course of the trial or within 12 weeks thereafter. Participant has received an IMP within the 12 weeks prior to the screening visit. Participant had brain surgery or traumatic brain injury within 1 year of screening. Participant has any other significant disease or disorder which, in the opinion of the investigator, may either put the participant, other participants, or site staff at risk because of participation in the trial, may influence the result of the trial, or may affect the participant's ability to take part in the trial. Any abnormalities identified following a physical examination of the participant that, in the opinion of the investigator, would jeopardize the safety of the participant if they took part in the trial Any history of suicidal behavior (lifelong) or any suicidal ideation of type 4 or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS) in the last 4 weeks or at screening or randomization Participant has donated blood during the past 12 weeks and is unwilling to abstain from donation of blood during the trial. Participant has any known or suspected history of alcohol or substance abuse or positive drugs of abuse test at screening (not justified by a known concurrent medication). Participant has previously been randomized into this trial. Participant has plans to travel outside their country of residence during the trial, unless the participant has confirmation that the IMP is permitted in the destination country/state

Ages Eligible for Study
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Minimum Age: 6 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 |
| --- | --- |
| Experimental: GWP42003-P 10 mg/kg/day<br>Participants will be stratified based on their age (6 to 11 years old, 12 to 17 years old), use of antipsychotics (on versus off), and region (North America versus Rest of the World) and will be randomized to receive 5 milligrams per kilogram per day (mg/kg/day) GWP42003-P for 1 week and then 10 mg/kg/day GWP42003-P for 11 weeks. | Drug: GWP42003-P<br>* GWP42003-P oral solution (100 milligrams per milliliter [mg/mL] cannabidiol [CBD] in sesame oil with anhydrous ethanol, ethanol [10% v/v] sweetener [sucralose], and strawberry flavoring), administered twice a day (morning and evening)<br>* Other names: CBD-OS;|
| Placebo Comparator: Placebo<br>Participants will be stratified based on their age (6 to 11 years old, 12 to 17 years old), use of antipsychotics (on versus off), and region (North America versus Rest of the World) and will be randomized to receive matching placebo for 12 weeks. | Drug: Placebo<br>* Oral placebo to match GWP42003-P oral solution containing sesame oil with anhydrous ethanol, sweetener (sucralose), strawberry flavoring, and beta carotene, administered twice a day (morning and evening)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Aberrant Behavior Checklist (ABC) Subscale Scores |  | Baseline; Day 85 | 
| Change from Baseline in Vineland Adaptive Behavior Scales-3 (VABS-3) Scores |  | Baseline; Day 85 | 
| Clinical Global Impression Improvement (CGI-I) Scores |  | Day 85 | 
| Change from Baseline in Clinical Global Impression Severity (CGI-S) Scores |  | Baseline; Day 85 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Severe Treatment-emergent Adverse Events |  | up to Day 106 | 
| Number of Participants with Clinically Significant Clinical Laboratory Parameter Values |  | up to Day 92 | 
| Number of Participants with Clinically Significant Vital Sign Values |  | up to Day 92 | 
| Number of Participants with Clinically Significant Physical Examination Procedure Findings |  | up to Day 85 | 
| Number of Participants with Clinically Significant 12-lead Electrocardiogram Findings |  | up to Day 85 | 
| Number of Participants with a Positive Response to Questions Regarding Suicidal Behavior Using the Columbia-Suicide Severity Rating Scale (C-SSRS) |  | up to Day 92 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cannabidiol oral solution, CBD-OS, GWP42003-P, Children, Adolescents