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Trial registered on ANZCTR


Registration number
ACTRN12621000760875
Ethics application status
Approved
Date submitted
27/04/2021
Date registered
18/06/2021
Date last updated
26/08/2022
Date data sharing statement initially provided
18/06/2021
Date results information initially provided
26/08/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Evaluating the Safety and Efficacy of Full-Spectrum Medicinal Cannabis (FEN164) in Children with ASD.
Scientific title
A Phase I/II Open-Label Study to Evaluate the Safety and Efficacy of Orally Administered Full-Spectrum Medicinal Cannabis Plant Extract 0.08% THC (FEN164) in Children with Autism Spectrum Disorder.
Secondary ID [1] 304066 0
FNX001/21
Universal Trial Number (UTN)
Trial acronym
Linked study record
None

Health condition
Health condition(s) or problem(s) studied:
Autism Spectrum Disorder 321711 0
Condition category
Condition code
Mental Health 319455 319455 0 0
Autistic spectrum disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Full-spectrum medicinal cannabis plant extract with 0.08% THC (FEN164).

FEN164 is an oil that will be administered orally over the course of the study.

The study involves the following phases:

• Baseline/Up-titration phase: Children will receive a baseline dose of 5mg/kg/day of FEN164 that will be increased weekly by 5mg/kg for a period of 4 weeks until the maximum tolerated dose or 20mg/kg is achieved.
• Treatment phase: Children will receive the maximum tolerated dose daily or 20mg/kg/day for either an 8-week period or they may choose to extend this up to 53 weeks (Extension phase).
• Down-titration phase: At the end of the Treatment Phase, children will receive a dosage that will be gradually decreased by 5mg/kg/week for a period of 4 weeks until the end of the study.
• Extension phase: Participants who choose to continue receiving the maximum tolerated dose beyond the set 8 weeks may do so for up to 53 weeks. They will undergo the Down-titration phase at the end of their Extension phase.
Intervention code [1] 320388 0
Treatment: Drugs
Comparator / control treatment
None
Control group
Uncontrolled

Outcomes
Primary outcome [1] 327325 0
Change in Clinical Global Impression Scale -Improvement (CGI-I)
This is a 7-point scale measuring symptom change from baseline.
Timepoint [1] 327325 0
Baseline (pre-dose), 4, 8, 12 & 16 weeks post-commencement of intervention.
Additional timepoints for Extension phase: Weeks 29, 41 & 53 post-commencement of intervention.
Primary outcome [2] 327326 0
Change in Vineland Adaptive Behaviour Scales, Third Edition (Vineland-3) Parent/Caregiver Form.
Used to measure adaptive functioning across three core domains (Communication, Daily Living Skills, and Socialization), and two optional domains (Motor Skills and Maladaptive Behaviour); items are rated on a 3-point scale (0=never; 1=sometimes; 2=usually or often). The core domains sum to a total Adaptive Behaviour Composite.

Timepoint [2] 327326 0
Baseline (pre-dose) and 16 weeks post-commencement of intervention.
Additional timepoints for Extension phase: Weeks 29, 41 & 53 post-commencement of intervention.
Primary outcome [3] 327618 0
Safety as assessed by Full Blood Examination
Timepoint [3] 327618 0
Baseline (pre-dose), 4, 8, 12 & 16 weeks post-commencement of intervention.
Additional timepoints for Extension phase: Weeks 29, 41 & 53 post-commencement of intervention.
Secondary outcome [1] 394619 0
Change in Social Responsiveness Scale, 2nd Edition (SRS-2), School-Age Form
Five domains are assessed including: Social Awareness, Social Cognition, Social Communication, Social Motivation, and Restricted Interests and Repetitive Behaviour. Items are scored on a 4-point scale (ranging from 1=not true to 4=almost always true).
Timepoint [1] 394619 0
Baseline (pre-dose) and 16 weeks post-commencement of intervention.
Additional timepoints for Extension phase: Weeks 29, 41 & 53 post-commencement of intervention.
Secondary outcome [2] 394621 0
Change in Anxiety, Depression and Mood Scale (ADAMS)
28 symptom items that resolve into five subscales labelled: Manic/Hyperactive Behaviour, Depressed Mood, Social Avoidance, General Anxiety, and Compulsive Behaviour. Items are rated on 4-point scale ranging from 0=not a problem to 3=severe problem.
Timepoint [2] 394621 0
Baseline (pre-dose) and 16 weeks post-commencement of intervention.
Additional timepoints for Extension phase: Weeks 29, 41 & 53 post-commencement of intervention.
Secondary outcome [3] 394623 0
Change in Sleep Disturbance Scale for Children (SDSC)
Six subscales including Disorders of Initiating and Maintaining Sleep, Sleep Breathing Disorders, Disorders of Arousal, Sleep Wake Transition Disorders, Disorders of Excessive Somnolence, and Sleep Hyperhydrosis. Items are rated on 5-point scale where 1=never and 5=always (daily). Subscale scores sum to equal a total score
Timepoint [3] 394623 0
Baseline (pre-dose), 4, 8, 12 & 16 weeks post-commencement of intervention.
Additional timepoints for Extension phase: Weeks 29, 41 & 53 post-commencement of intervention.
Secondary outcome [4] 394624 0
Change in Clinical Global Impression-Severity (CGI-S)
Reflects clinician’s impression of severity of illness on a 7-point scale ranging from 1=not at all to 7=among the most extremely ill.
Timepoint [4] 394624 0
Baseline (pre-dose), 4, 8, 12 & 16 weeks post-commencement of intervention.
Additional timepoints for Extension phase: Weeks 29, 41 & 53 post-commencement of intervention.
Secondary outcome [5] 394625 0
Change in Autism Family Experience Questionnaire (AFEQ)
Parent/Caregiver form used to measure impact of autism interventions on family experience and quality of life. Items are rated on a 5-point scale where 1=always and 5=never.
Timepoint [5] 394625 0
Baseline (pre-dose) and 16 weeks post-commencement of intervention.
Additional timepoints for Extension phase: Weeks 29, 41 & 53 post-commencement of intervention.
Secondary outcome [6] 394626 0
Change in Anxiety Scale for Children - Autism Spectrum Disorder - Parent Versions (ASC-ASD-P)
Parent/Caregiver form developed to detect symptoms of anxiety in youth with ASD. Composed of four subscales (Performance Anxiety, Uncertainty, Anxious Arousal, and Separation Anxiety), items are rated on a 4-point scale (0=never and 3=always). Subscales sum to equal a total score.
Timepoint [6] 394626 0
Baseline (pre-dose), 4, 8, 12 & 16 weeks post-commencement of intervention.
Additional timepoints for Extension phase: Weeks 29, 41 & 53 post-commencement of intervention.
Secondary outcome [7] 394627 0
Change in Anxiety Scale for Children - Autism Spectrum Disorder (ASC-ASD-C) - Child Versions
Child form developed to detect symptoms of anxiety in youth with ASD. Composed of four subscales (Performance Anxiety, Uncertainty, Anxious Arousal, and Separation Anxiety), items are rated on a 4-point scale (0=never and 3=always). Subscales sum to equal a total score.
Timepoint [7] 394627 0
Baseline (pre-dose), 4, 8, 12 & 16 weeks post-commencement of intervention.
Additional timepoints for Extension phase: Weeks 29, 41 & 53 post-commencement of intervention.
Secondary outcome [8] 395947 0
Primary Outcome: Safety as assessed by Liver Function Tests
Timepoint [8] 395947 0
Baseline (pre-dose), 4, 8, 12 & 16 weeks post-commencement of intervention.
Additional timepoints for Extension phase: Weeks 29, 41 & 53 post-commencement of intervention.
Secondary outcome [9] 395948 0
Primary Outcome: Safety as assessed by Kidney Function Tests
Timepoint [9] 395948 0
Baseline (pre-dose), 4, 8, 12 & 16 weeks post-commencement of intervention.
Additional timepoints for Extension phase: Weeks 29, 41 & 53 post-commencement of intervention.

Eligibility
Key inclusion criteria
• Participant is aged 8 years to 17 years (inclusive)
• Participant is at a healthy weight at the discretion of the Principal Investigator.
• Parents or caregivers can give informed consent for participation in the trial with assent from individuals with autism.
• Participants can comply with trial requirements.
• According the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria the participant has a diagnosis of Level 2 or 3 Autism Spectrum Disorder (ASD) confirmed by Autism Diagnostic Observational Schedule (ADOS-2) criteria
• All treatments including medications and therapies for ASD related symptoms must have been stable for 4 weeks before enrolment and for the duration of the trial wherever possible.
• Participants must be able to swallow liquid.
• Consent giver must be able to understand the requirements of the study.
Minimum age
8 Years
Maximum age
17 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Current diagnosis of bipolar disorder, psychosis, schizophrenia, schizoaffective disorder, or active major depression
• Has a diagnosis other than ASD that dominates the clinical presentation (e.g., Attention Deficit Hyperactivity Disorder [ADHD])
• Has a degenerative condition
• Changes in anticonvulsive therapy within the last 12 weeks
• Taking omeprazole, lansoprazole, tolbutamide, warfarin, sirolimus, everolimus, temsirolimus, tacrolimus, clobazam, 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
• 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 with 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 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 behaviour (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 enrolled into this trial.
• Participant has plans to travel outside their country of residence during the trial, unless the participant has confirmation that the product is permitted in the destination country/state

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1 / Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Wilcoxon Signed-Rank Test and the Paired t-test to be used to assess the statistical significance.

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 19203 0
Monash Children’s Hospital - Clayton
Recruitment postcode(s) [1] 33775 0
3168 - Clayton

Funding & Sponsors
Funding source category [1] 308450 0
Commercial sector/Industry
Name [1] 308450 0
Fenix Innovation Group
Country [1] 308450 0
Australia
Funding source category [2] 312128 0
Commercial sector/Industry
Name [2] 312128 0
Neurotech International Limited
Country [2] 312128 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Fenix Innovation Group
Address
5A Hartnett Court, Mulgrave VIC Australia 3170
Country
Australia
Secondary sponsor category [1] 309286 0
None
Name [1] 309286 0
Address [1] 309286 0
Country [1] 309286 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308403 0
Monash Health Human Research Ethics Committee
Ethics committee address [1] 308403 0
246 Clayton Road, Clayton VIC Australia 3168
Ethics committee country [1] 308403 0
Australia
Date submitted for ethics approval [1] 308403 0
15/04/2021
Approval date [1] 308403 0
20/04/2021
Ethics approval number [1] 308403 0

Summary
Brief summary
This is a 17 to 57-week open-label study to evaluate the safety and efficacy of full-spectrum medicinal cannabis plant extract containing only 0.08% THC (FEN164) in children with Autism Spectrum Disorder (ASD).

The purpose of this study is to determine how safe and effective FEN164 is in patients with ASD when treated with 20mg/kg/day for an 8 week period.

Participants will commence treatment with a daily dose of 5mg/kg of FEN164. This will gradually increase over a four-week period until the maximum tolerated daily dose or 20mg/kg per day is achieved (Up-titration phase). Participants will continue to receive their respective maximum dose for eight (8) weeks (Treatment phase). Participants who wish to continue receiving their maximum tolerated dose beyond the 8-week Treatment phase may do so for up to fifty-three (53) weeks (Extension phase). At the end of the Treatment or Extension phase, participants will be gradually decreased by 5 mg/kg for a period of 4 weeks until the end of their participation (Down-titration phase).

Safety will be measured and monitored by performing full blood examinations and liver and renal function tests throughout the study.

Efficacy will be measured and monitored by performing participant- and psychologist- led questionnaires specific to measuring changes in the behaviour of patients with ASD.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 110598 0
Prof Michael Fahey
Address 110598 0
Monash Children's Hospital
246 Clayton Road, Clayton VIC Australia 3168
Country 110598 0
Australia
Phone 110598 0
+61 3 8572 3757
Fax 110598 0
Email 110598 0
michael.fahey@monash.edu
Contact person for public queries
Name 110599 0
Ms Yelda Ogru
Address 110599 0
Fenix Innovation Group
5A Hartnett Court, Mulgrave VIC Australia 3170
Country 110599 0
Australia
Phone 110599 0
+61418250292
Fax 110599 0
Email 110599 0
yelda@fenixinnovationgroup.com
Contact person for scientific queries
Name 110600 0
Ms Yelda Ogru
Address 110600 0
Fenix Innovation Group
5A Hartnett Court, Mulgrave VIC Australia 3170
Country 110600 0
Australia
Phone 110600 0
+61418250292
Fax 110600 0
Email 110600 0
yelda@fenixinnovationgroup.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
IPD will not be shared as per commercial in confidence restrictions.


What supporting documents are/will be available?

No Supporting Document Provided
Current supporting documents:



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.