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Trial registered on ANZCTR


Registration number
ACTRN12622001398796
Ethics application status
Approved
Date submitted
19/10/2022
Date registered
1/11/2022
Date last updated
1/02/2023
Date data sharing statement initially provided
1/11/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Evaluating the Efficacy of Full-Spectrum Medicinal Cannabis Plant Extract 0.08% THC (NTI164) in Young People with Autism Spectrum Disorder, a Double-Blind, Randomised and Controlled-to-Open-Label Study.
Scientific title
A Phase II/III Double-Blind, Randomised and Controlled-to-Open-Label Study Assessing the Efficacy of Full-Spectrum Medicinal Cannabis Plant Extract 0.08% THC (NTI164) on the Severity of Autism Spectrum Disorder in Young People
Secondary ID [1] 308228 0
NTIASD2
Universal Trial Number (UTN)
Trial acronym
Linked study record
Follow-up study to registration record ACTRN12621000760875

Health condition
Health condition(s) or problem(s) studied:
Autism Spectrum Disorder 327987 0
Condition category
Condition code
Mental Health 325047 325047 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 (NTI164).

NTI164 is an oil that will be administered orally over the course of the study.

The study involves the following phases:

• Randomised Controlled Phase (duration = 8 weeks)
At the beginning of the study, participants will be randomised into either the active group or placebo group. Both groups will commence a double-blinded baseline dose of either 5mg/kg/day of NTI164 or Placebo that will be increased weekly by 5mg/kg for a period of 4 weeks until the maximum tolerated dose or 20/mg/kg/day is achieved.

At the end of the 8-week period, both study groups will be unblinded and the primary endpoint of the study will be assessed.

• Open-Label Phase (duration = 8 weeks)
Participants who received Placebo will commence NTI164. This involves a 4-week weekly up-titration of 5mg/kg until the maximum tolerated dose or 20/mg/kg/day is achieved. These participants will then continue to receive their maximum tolerated dose for an additional 4-weeks.

Participants who received NTI164 during the Randomised Controlled phase will continue receiving their maximum tolerated dose during the Open-label phase for 8-weeks.

• Wash-out phase (duration = 2 weeks)
At the end of the 16 weeks, participants have the option of ending their participation and undergoing a 2-week down-titration of NTI164. The dosage down-titration will be dependent on the maximum tolerated dose of each participant and at the discretion of the Principal Investigator.

• Extension phase (duration = 36 weeks)
Participants who choose to continue receiving NTI164 beyond the duration of the study may do so for an additional 38 weeks. They will undergo the 2-week Down-titration phase at the end of their Extension phase.

The minimum duration of this study is 18 weeks and the maximum duration is 54 weeks.

Monitoring of completion of daily online drug administration forms plus accountability of returned study product and packaging at each visit, will be conducted to ensure protocol adherence.
Intervention code [1] 324687 0
Treatment: Drugs
Comparator / control treatment
The control treatment will be a virgin olive oil placebo that has a similar appearance to the active treatment.
Control group
Placebo

Outcomes
Primary outcome [1] 332868 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 [1] 332868 0
Primary endpoint: Baseline (pre-dose), 4 & 8 weeks post-commencement of treatment.
Secondary outcome [1] 414900 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 [1] 414900 0
Baseline (pre-dose) and 16 weeks post-commencement of treatment. Additional timepoints for Extension phase: Weeks 28, 40 & 52 post-commencement of treatment.
Secondary outcome [2] 414901 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 [2] 414901 0
Baseline (pre-dose) and 16 weeks post-commencement of treatment. Additional timepoints for Extension phase: Weeks 28, 40 & 52 post-commencement of treatment.
Secondary outcome [3] 414902 0
Change in Clinical Global Impression Scale -Improvement (CGI-I) This is a 7-point scale measuring symptom change from baseline.
Timepoint [3] 414902 0
Baseline (pre-dose), 4, 8, 12 & 16 weeks post-commencement of treatment. Additional timepoints for Extension phase: Weeks 28, 40 & 52 post-commencement of treatment.
Secondary outcome [4] 414903 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 [4] 414903 0
Baseline (pre-dose) and 16 weeks post-commencement of treatment. Additional timepoints for Extension phase: Weeks 28, 40 & 52 post-commencement of treatment.
Secondary outcome [5] 414904 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 [5] 414904 0
Baseline (pre-dose), 4, 8, 12 & 16 weeks post-commencement of treatment. Additional timepoints for Extension phase: Weeks 28, 40 & 52 post-commencement of treatment.
Secondary outcome [6] 414905 0
Change in Anxiety Scale for Children - Autism Spectrum Disorder - A 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] 414905 0
Baseline (pre-dose), 4, 8, 12 & 16 weeks post-commencement of treatment. Additional timepoints for Extension phase: Weeks 28, 40 & 52 post-commencement of treatment.
Secondary outcome [7] 414906 0
Change in Clinical Global Impression of Change (CGI-C) Target Behaviour - Reflects clinician’s impression of change of behaviour on a 7-point scale ranging from 1=not at all to 7=very severe problem. Provided as Baseline and Post-Baseline questionnaires.
Timepoint [7] 414906 0
Baseline (pre-dose), 4, 8, 12 & 16 weeks post-commencement of treatment. Additional timepoints for Extension phase: Weeks 28, 40 & 52 post-commencement of treatment.
Secondary outcome [8] 414907 0
Change in Clinical Global Impression of Change in Attention (CGI-CA) - Reflects clinician’s impression of change in attention on a 7-point scale ranging from 1=not at all to 7=very severe problem.
Timepoint [8] 414907 0
Baseline (pre-dose), 4, 8, 12 & 16 weeks post-commencement of treatment. Additional timepoints for Extension phase: Weeks 28, 40 & 52 post-commencement of treatment.
Secondary outcome [9] 415062 0
Safety as assessed by Full Blood Examination
Timepoint [9] 415062 0
Baseline (pre-dose), 8 & 16 weeks post-commencement of intervention. Additional timepoints for Extension phase: Weeks 28, 40 & 52 post-commencement of treatment.
Secondary outcome [10] 415063 0
Safety as assessed by Liver Function Tests
Timepoint [10] 415063 0
Baseline (pre-dose), 8 & 16 weeks post-commencement of intervention. Additional timepoints for Extension phase: Weeks 28, 40 & 52 post-commencement of treatment.
Secondary outcome [11] 415064 0
Safety as assessed by Kidney Function Tests
Timepoint [11] 415064 0
Baseline (pre-dose), 8 & 16 weeks post-commencement of intervention. Additional timepoints for Extension phase: Weeks 28, 40 & 52 post-commencement of treatment.

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 greater than or equal to 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
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is concealed utilising central randomisation by computer.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A computerised sequence generator will be used to randomly allocate participants into groups.
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 2 / Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/02/2023
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
54
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 312483 0
Commercial sector/Industry
Name [1] 312483 0
Fenix Innovation Group
Country [1] 312483 0
Australia
Funding source category [2] 312484 0
Commercial sector/Industry
Name [2] 312484 0
Neurotech International Limited
Country [2] 312484 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Fenix Innovation Group
Address
5A Hartnett Close, Mulgrave VIC Australia 3170
Country
Australia
Secondary sponsor category [1] 314069 0
None
Name [1] 314069 0
Address [1] 314069 0
Country [1] 314069 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311824 0
Monash Health Human Research Ethics Committee
Ethics committee address [1] 311824 0
246 Clayton Road, Clayton VIC Australia 3168
Ethics committee country [1] 311824 0
Australia
Date submitted for ethics approval [1] 311824 0
28/09/2022
Approval date [1] 311824 0
17/10/2022
Ethics approval number [1] 311824 0

Summary
Brief summary
This is an 18 to 54 week study assessing the efficacy of Full-Spectrum Medicinal Cannabis Plant Extract 0.08% THC (NTI164) on the severity of autism spectrum disorder in young people.

The purpose of this study is to determine the effectiveness of NTI164 in patients with ASD when treated with 20mg/kg/day for 8 - 54 weeks.

The study comprises of an 8-week double-blinded randomised controlled treatment period followed by an 8-week open-label maintenance period followed by a 2-week wash-out period. Participants who wish to continue receiving the study treatment beyond the 16 week period may do so for up to fifty-two weeks (Extension phase)

Efficacy will be measured and monitored by performing participant- and psychologist- led questionnaires specific to measuring changes in the behaviour of patients with ASD.

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

Additional assessments include microbiome and inflammatory marker assessments.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 122498 0
Prof Michael Fahey
Address 122498 0
Monash Children's Hospital 246 Clayton Road, Clayton VIC Australia 3168
Country 122498 0
Australia
Phone 122498 0
+61 3 8572 3757
Fax 122498 0
Email 122498 0
michael.fahey@monash.edu
Contact person for public queries
Name 122499 0
Ms Kanan Sharma
Address 122499 0
Monash Children's Hospital 246 Clayton Road, Clayton VIC Australia 3168
Country 122499 0
Australia
Phone 122499 0
+61 03 8572 3581
Fax 122499 0
Email 122499 0
MonashchildrensCTC@monashhealth.org
Contact person for scientific queries
Name 122500 0
Ms Kanan Sharma
Address 122500 0
Monash Children's Hospital 246 Clayton Road, Clayton VIC Australia 3168
Country 122500 0
Australia
Phone 122500 0
+61 03 8572 3581
Fax 122500 0
Email 122500 0
MonashchildrensCTC@monashhealth.org

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



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.