Clinical trial NCT04745026: Trial to Investigate the Safety and Efficacy of Cannabidiol Oral Solution (GWP42003-P; CBD-OS) in Children and Adolescents With Autism Spectrum Disorder
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Autism Spectrum Disorder
Keywords: Cannabidiol oral solution
CBD-OS
GWP42003-P
Children
Adolescents
Lead sponsor: Jazz Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2021-02-09
Enrollment: 103
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: 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

Primary outcomes:
measure: Change From Baseline in Aberrant Behavior Checklist (ABC) Subscale Total Scores
timeFrame: Baseline up to Week 12
measure: Change From Baseline in Vineland Adaptive Behavior Scales-3 (VABS-3) Scores
timeFrame: Baseline up to Week 12
measure: Number of Patients Per Clinical Global Impression Improvement (CGI-I) Category
timeFrame: Day 85
measure: Change From Baseline in Clinical Global Impression Severity (CGI-S) Scores
timeFrame: Baseline up to Week 12
Secondary outcomes:
measure: Number of Participants Reporting Treatment-emergent Adverse Events
timeFrame: Baseline up to Week 12
measure: Mean Change From Baseline in Hematology Clinical Laboratory Levels
timeFrame: Baseline up to Week 9 (end of taper/withdrawal)
measure: Mean Percentage Change From Baseline in Hematology Clinical Laboratory Levels
timeFrame: Baseline up to Week 9 (end of taper/withdrawal)
measure: Mean Change From Baseline in Hemoglobin Levels
timeFrame: Week 9 (end of taper/withdrawal)
measure: Mean Change From Baseline in Erythrocyte Mean Corpuscular Hemoglobin Levels
timeFrame: Week 9 (end of taper/withdrawal)
measure: Mean Change From Baseline in Erythrocyte Mean Corpuscular Volume Levels
timeFrame: Week 9 (end of taper/withdrawal)
measure: Number of Patients With Clinically Significant Vital Sign Values
timeFrame: Post-baseline up to 12 weeks
measure: Number of Patients With Clinically Significant Physical Examination Procedure Findings
timeFrame: Baseline up to Day 85 post-baseline
measure: Number of Patients With Clinically Significant 12-lead Electrocardiogram Findings
timeFrame: Baseline up to Day 85 post-baseline
measure: Number of Participants Reporting Suicidal Ideation or Behavior Using the Columbia-Suicide Severity Rating Scale (C-SSRS)
timeFrame: Baseline up to Day 92
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Southwest Autism Research and Resource Center (SARRRC)
state: Arizona
city: La Jolla
country: United States
facility: UCSD School of Medicine
state: California
city: Los Angeles
country: United States
facility: UCLA Neuropsychiatric Institute
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Orlando
country: United States
facility: APG Research, LLC
state: Florida
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Lexington
country: United States
facility: Massachusetts General Hospital (Lurie Center for Autism)
state: Massachusetts
city: Staten Island
country: United States
facility: Richmond Behavioral Associates
state: New York
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Houston
country: United States
facility: Red Oak Psychiatry Associates, PA
state: Texas
city: Seattle
country: United States
facility: Seattle Children's Research Institute
state: Washington
city: Clayton
country: Australia
facility: Monash Medical Centre
city: South Brisbane
country: Australia
facility: Queensland Children's Hospital
city: Ajax
country: Canada
facility: The Kids Clinic
state: Ontario
city: Ottawa
country: Canada
facility: Center for Pediatric Excellence
state: Ontario
city: Freiburg
country: Germany
facility: Klinik fur Psychiatrie, Psychotherapie und Psychosomatik im Kindes und Jugendalter
city: Mannheim
country: Germany
facility: Zentralinstitut fuer Seelische Gesundheit
city: Barcelona
country: Spain
facility: Instituto Global de Atencion Integral del Neurodesarrollo (IGAIN)
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Sabadell
country: Spain
facility: Corporacio Sanitaria Parc Tauli
city: Glasgow
country: United Kingdom
facility: University of Glasgow Institute of Health and Wellbeing
city: London
country: United Kingdom
facility: Institute of Psychiatry, King's College London
Study officials:
References: