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

Prior treatment

• Changes in anticonvulsive therapy within the last 12 weeks
• Currently taking more than 2 anti-epileptic drugs (AEDs)
• 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 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 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.

Other illness

• 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
• Participant has any known or suspected hypersensitivity to cannabinoids or any of the excipients of the IMP, such as sesame oil.
• 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 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

Lab values

• 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.

Other

• Taking sirolimus, everolimus, temsirolimus, or tacrolimus
• Taking clobazam
• Taking omeprazole, lansoprazole, tolbutamide, or warfarin
• Taking repaglinide, pioglitazone, rosiglitazone, montelukast, bupropion, or efavirenz
• 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.
• 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
• Participant has donated blood during the past 12 weeks and is unwilling to abstain from donation of blood during the 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

• 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.