NTI164 bij Autismespectrumstoornis (Beyond Harmony)
Een fase III dubbelblinde, gerandomiseerde, placebo-gecontroleerde studie naar de werkzaamheid en veiligheid van NTI164 bij kinderen en jongvolwassenen met autismespectrumstoornis
This is a double-blind, randomised, placebo-controlled study investigating the efficacy of a full-spectrum medicinal cannabis plant extract on core and associated ASD symptoms over placebo. Participants will be randomly allocated to either NTI164 or placebo at a 1:1 ratio and blood samples will be collected and surveys completed at baseline and Week 16. This study will expand efficacy and safety data of NTI164 and provide additional mechanism of action data of NTI164 in this patient cohort.
Studie Overzicht
Toestand
Interventie / Behandeling
Gedetailleerde beschrijving
Participants will be recruited from sites across Australia and will have a diagnosis of ASD Level II or III, as well as satisfying other inclusion/exclusion criteria. The primary objective is to assess efficacy of 16 weeks of daily oral administration of NTI164 on core ASD symptoms compared to placebo. The secondary objectives are to further expand the safety data of NTI164 in this patient cohort, and assess the changes in other associated symptoms of ASD following NTI164.
Studietype
Inschrijving (Geschat)
Fase
- Fase 3
Contacten en locaties
Studiecontact
- Naam: Michael C Fahey
Studie Contact Back-up
- Naam: Kanan Sharma
- Telefoonnummer: +61395946666
- E-mail: monashchildrensctc@monashhealth.org
Studie Locaties
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Queensland
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Brisbane, Queensland, Australië
- Children's Hospital Queensland
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Contact:
- Michael Duhig
- Telefoonnummer: 61+ 07 3068 2593
- E-mail: CHQ_CCTRND@health.qld.gov.au
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Hoofdonderzoeker:
- Helen Heussler
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Sunshine Coast, Queensland, Australië, 4575
- Sunshine Coast University Hospital
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Contact:
- Roni Cole
- Telefoonnummer: 61+ 07 5202 0000
- E-mail: sc-wcs-research@health.qld.gov.au
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Hoofdonderzoeker:
- Ianthe Mills
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Victoria
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Clayton, Victoria, Australië, 3168
- Monash Health
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Contact:
- Kanan Sharma
- Telefoonnummer: +61395946666
- E-mail: MonashChildrensCTC@monashhealth.org
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Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
Accepteert gezonde vrijwilligers
Geslachten die in aanmerking komen voor studie
Beschrijving
Inclusion Criteria:
- Participant is aged 6 years to 21 years (inclusive).
- Participant is at a healthy weight at the discretion of the Principal Investigator.
- Written informed consent from parent or legal guardian according to the local law.
- 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 II or III ASD confirmed by a validated assessment tool.
- All treatments including medications and therapies for ASD related symptoms must have been stable for 12 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.
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., 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, vasectomised 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 jeopardise 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 12 weeks or at screening or randomisation.
- 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.
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: Gerandomiseerd
- Interventioneel model: Parallelle opdracht
- Masker: Verviervoudigen
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
|---|---|
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Placebo-vergelijker: Placebo
Placebo |
Placebo oil suspension |
|
Experimenteel: Active
NTI164 |
A CBDA-dominant full-spectrum medicinal cannabis plant extract with extremely low THC.
Andere namen:
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Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
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Vineland Adaptive Behaviour Scales, 3rd Edition (Vineland-3)
Tijdsspanne: Baseline, Week 16
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Used to measure functioning across 3 core domains, Communication, Daily Living Skills, and Socialisation, as well as 2 optional domains, Motor Skills and Maladaptive Behaviour. The core domains sum to a total Adaptive Behaviour Composite. Scores are between 20-160, higher scores indicate better outcomes. |
Baseline, Week 16
|
Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
|
Social Responsiveness Scale, 2nd Edition (SRS-2)
Tijdsspanne: Baseline, Week 16
|
Captures overall change in core ASD symptoms across domains including social awareness, social cognition, social communication, social motivation, and restricted and repetitive behaviours. Scores are between 0-195, and higher scores indicate greater impairment. |
Baseline, Week 16
|
|
Clinical Global Impression - Improvement (CGI-I)
Tijdsspanne: Baseline, Week 16
|
Provides a clinician-rated global assessment of improvement at a given time point following an intervention. 1-3 = improvement, 4 = no change, 5-7 = worsening. |
Baseline, Week 16
|
|
Clinical Global Impression - Severity (CGI-S)
Tijdsspanne: Baseline, Week 16
|
Evaluates a clinician's impression of disease severity at a given time point from a scale of 1-7. A higher score indicates greater impairment/disease severity. |
Baseline, Week 16
|
|
Anxiety, Depression, and Mood Scale (ADAMS)
Tijdsspanne: Baseline, Week 16
|
Measures emotional and behavioural disturbances frequently comorbid with ASD. Assesses 5 domains (Manic/hyperactive Behaviour, Depressed Mood, Social Avoidance, General Anxiety, and Compulsive Behaviour). Scores are between 0-84, with higher scores indicating greater impairment. |
Baseline, Week 16
|
|
Autism Family Experience Questionnaire (AFEQ)
Tijdsspanne: Baseline, Week 16
|
Captures caregiver perceptions of changes in family impact, child wellbeing, and support burden. Scores range from 48-240, with higher scores indicating worse family outcomes. |
Baseline, Week 16
|
|
Sleep Disturbances Scale for Children (SDSC)
Tijdsspanne: Baseline, Week 16
|
Evaluates treatment-related changes in sleep quality and sleep-wake behaviours. Assesses 6 domains (Disorders of Initiating and Maintaining Sleep, Sleep Breathing Disorders, Disorders of Arousal, Sleep Wake Transition Disorders, Disorders of Excessive Somnolence, and Sleep Hyperhidrosis). Scores range from 26-130, with higher scores indicating greater impairment and issues around sleep. |
Baseline, Week 16
|
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EQ-5D-Y-5L
Tijdsspanne: Baseline, Week 16
|
Measures broader wellbeing and day-to-day function, as well as quality of life (QoL), from a caregiver-reported perspective. Assesses health in 5 domains (Mobility, Usual Activities, Self-care, Pain/discomfort, and Anxiety/depression), and QoL. Scores range from 0-1, with 0 = the worst health possible and 1 = the best possible health state. The higher the score, the better the health state. |
Baseline, Week 16
|
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Anxiety Scale for Children with ASD, Parent edition (ASC-ASD-P)
Tijdsspanne: Baseline, Week 16
|
Evaluates changes in anxiety symptoms and emotional regulation. It is used to detect symptoms of anxiety in youth with ASD and assesses 4 domains (Performance Anxiety, Uncertainty, Anxious Arousal, and Separation Anxiety). Scores range from 0-72, with higher scores indicating greater impairment. |
Baseline, Week 16
|
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Aberrant Behaviour Checklist (ABC)
Tijdsspanne: Baseline, Week 16
|
Assesses challenging behaviours and behavioural regulation relevant to ASD functioning. Measures impairment across 5 domains (Irritability, Lethargy/social Withdrawal, Stereotypic Behaviour, Hyperactivity/non-compliance, and Inappropriate Speech. Scores range from 0-174, with higher scores indicating greater impairment. |
Baseline, Week 16
|
Andere uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
|
Research samples - transcriptomics
Tijdsspanne: Baseline, Week 16
|
To further clarify the mechanism of action of NTI164, both bulk and single-cell RNA sequencing will be performed on peripheral blood mononuclear cells (PBMCs) from patients at specified time points. This will provide additional information regarding which genes are being expressed in patients at either abnormally low or high levels compared to a non-ASD population, and the effects NTI164 has on gene expression. This workflow includes RNA extraction, depletion of ribosomal RNA via hybrid capture, library preparation, and sequencing. Cleaned sequence reads will then be aligned against the Homo sapiens genome (Build version hg38) and STAR aligner (v2.5.3a) will be used to map unique reads to the genomic sequences. This is exploratory so genes of interest cannot be identified in advance. |
Baseline, Week 16
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Research bloods - proteomics (and phosphoproteomics)
Tijdsspanne: Baseline, Week 16
|
To further clarify the mechanism of action of NTI164, proteomics and phosphoproteomics will be performed on peripheral blood mononuclear cells (PBMCs) from patients at specified time points. This will provide additional information regarding which proteins are being expressed at either abnormally low or high levels compared to a non-ASD population, as well as how extensively these proteins are phosphorylated compared to a non-ASD population, and the effects NTI164 has on protein expression and phosphorylation. Samples will be tagged using the TMTpro system and hydrophilic ion liquid chromatography fractionation performed. This is exploratory so proteins of interest cannot be identified in advance. |
Baseline, Week 16
|
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Research bloods - Methylomics
Tijdsspanne: Baseline, Week 16
|
To further clarify the mechanism of action of NTI164, methylomics will be performed on whole blood from patients at specified time points. This will provide additional information on methylation patterns (e.g. addition of a methyl group to histones or DNA) in patients compared to non-patients, and how NTI164 effects this type of epigenetic modification and how genes of interest may be regulated. This is exploratory so patterns of interest cannot be identified in advance. Genome-wide methylation will be assessed using the Illumina MethylationEPIC v2.0 BeadChip (or the latest version if a new version is available to the study team at the time of analysis). |
Baseline, Week 16
|
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Research bloods - cytokine assay
Tijdsspanne: Baseline, Week 16
|
To further clarify the mechanism of action of NTI164, a cytokine assay investigating a panel of inflammatory markers will be performed on plasma from patients at specified time points. The cytokine assay will likely be the LEGENDplex Human Neuroinflammation Panel 1 (13 plex). Cytokines investigated with this panel include VILIP-1, CCL2, sTREM-2, b-NGF, TGF-b1, TNF-a, IL-6, s-TREM-1, sRAGE, CX3CL1, VEGF, BDNF, and IL-18. |
Baseline, Week 16
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Medewerkers en onderzoekers
Sponsor
Medewerkers
Studie record data
Bestudeer belangrijke data
Studie start (Geschat)
Primaire voltooiing (Geschat)
Studie voltooiing (Geschat)
Studieregistratiedata
Eerst ingediend
Eerst ingediend dat voldeed aan de QC-criteria
Eerst geplaatst (Werkelijk)
Updates van studierecords
Laatste update geplaatst (Werkelijk)
Laatste update ingediend die voldeed aan QC-criteria
Laatst geverifieerd
Meer informatie
Termen gerelateerd aan deze studie
Trefwoorden
Aanvullende relevante MeSH-voorwaarden
Andere studie-ID-nummers
- NTIASD3
- FENASD3 (Andere identificatie: Fenix Innovation Group)
Informatie over medicijnen en apparaten, studiedocumenten
Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel
Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct
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