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Trial registered on ANZCTR


Registration number
ACTRN12618001956291
Ethics application status
Approved
Date submitted
17/09/2018
Date registered
4/12/2018
Date last updated
27/11/2019
Date data sharing statement initially provided
4/12/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
A study to investigate the Safety and Tolerability of AB-2004 in a Pediatric Autism Spectrum Disorder Population
Scientific title
A Single-Arm, Single Sequence, Multiple Ascending Dose Study of the Safety and Tolerability of AB-2004 in a Pediatric Autism Spectrum Disorder Population
Secondary ID [1] 294908 0
AXL-1224-2004-001
Universal Trial Number (UTN)
U1111-1218-4954
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pediatric Autism Spectrum Disorder 307870 0
Condition category
Condition code
Human Genetics and Inherited Disorders 306912 306912 0 0
Other human genetics and inherited disorders
Mental Health 308546 308546 0 0
Autistic spectrum disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
It is now known that communication between the bacteria in your gut and your brain is important to the way in which your brain develops and functions. Additionally, your gut bacteria have been shown to have an impact on behavior. Studies have shown that the bacteria in the gut of children with ASD differs from the bacteria in the gut of typically developing children. The changes seen in the gut bacteria of children with ASD can increase the “leakiness” of the gut, making it easier for chemical substances produced by the bacteria to reach the brain and potentially affect the function of the brain. Axial Biotherapeutics has shown in animal studies that the chemical substances produced by certain gut bacteria may affect the core and non-core symptoms commonly found in ASD. Based on this research Axial Biotherapeutics has developed this study to be an open-label, outpatient, multiple ascending dose study of AB-2004 in a paediatric population diagnosed with autism spectrum disorder (ASD) accompanied by gastrointestinal symptoms. The primary outcome is to assess the safety and tolerability of AB-2004 administered daily over a period of 8 weeks as assessed by the frequency and severity of adverse events and laboratory abnormalities. Secondary outcomes include assessments of the effects of AB-2004 on intestinal permeability, systemic levels of host and microbially-derived metabolites, biomarkers of systemic inflammation, the fecal microbiome profile, gastrointestinal signs and symptoms, core behaviours and affect (particularly anxiety and irritability) and the measures of brain connectivity and white matter integrity.
There will be a single treatment arm (AB-2004) consisting of three dosing periods. Total study duration will be 14-16 weeks.

Treatment with AB-2004 administered orally, at approximately the same times each day (three times a day). AB-2004 is a granular, free flowing powder in a sachet that can be mixed into a snack and eaten.
Weight is used to determine the starting dose of AB-2004. Participants weighing greater than or equal to 50 kg will receive 0.75 gm TID, while subjects weighing greater than or equal to 30 kg and less than 50 kg will receive 0.5 gm TID as a starting dose.

In order to better facilitate adherence to the dosing regimen it is recommended that the either product be mixed with the participant’s favourite soft foods (yogurt).
Intervention code [1] 301245 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 305927 0
To assess the safety and tolerability of AB-2004 administered daily over a period of 8 weeks as assessed by the frequency and severity of adverse events, laboratory abnormalities.
Timepoint [1] 305927 0
Monitored daily through Screening Visit and 28 days after the last dose of study treatment for each treatment arm. The primary possible AEs being looked for are constipation/abdominal pain. Adverse events associated with AB-2004 will be captured via self-reported changes in bowel habits and pain.
Secondary outcome [1] 347054 0
Changes in measures of intestinal permeability as assessed in Urine Lactulose and Mannitol Test
Timepoint [1] 347054 0
Monitored at Screening Visit, End of treatment(V5 day 57(+5)) and follow -up(V6 85(+5)).
Secondary outcome [2] 352577 0
Changes in systemic exposure to host and microbial metabolites, assessed, in part, by measurements of serum and/or urinary 4-EPS, p-CS, 5-HT and 5HIAA levels. It is the composite secondary outcome
Timepoint [2] 352577 0
Monitored through Screening Visit and 29 days after the last dose of study treatment for each treatment arm frequency of assessments: weekly
Secondary outcome [3] 352578 0
Changes in mood, as assessed by the Pediatric Anxiety Rating Scale (PARS) & Child and Adolescent Inventory 5 (CASI-5), Anxiety & Depression subscales
Timepoint [3] 352578 0
Monitored through Screening Visit and 29 days after the last dose of study treatment for each treatment arm frequency of assessments: weekly
Secondary outcome [4] 353634 0
Changes in symptom severity assessments: Repetitive Behaviors Scale - Revised (RBS-R)
Timepoint [4] 353634 0
Monitored through Screening Visit and 29 days after the last dose of study treatment for each treatment arm frequency of assessments: weekly
Secondary outcome [5] 367380 0
Changes in brain connectivity, including resting connectivity, and white matter integrity, including fractional anisotropy assessment of limbic structures derived from whole brain magnetic resonance imaging (MRI) / diffusion tensor imaging (DTI) (targeting 10 subjects).
Timepoint [5] 367380 0
Monitored through Screening Visit and 28 days after the last dose of study treatment for each treatment arm frequency of assessments: weekly

Eligibility
Key inclusion criteria
Participants must meet all inclusion criteria's (and not meet exclusion criteria) to be enrolled in the study. Following are the key Inclusion Criteria -
Inclusion Criteria:
1. Clinically diagnosed, documented Autism Spectrum Disorder (DSM-V criteria)
confirmed with ADOS-2 at Visit 1 or within 18 months prior to Visit 1.
2. Adolescents greater than or equal to 12 and less than 18 years of age at the time of consent
3. History of gastrointestinal symptoms (diarrhea, constipation, abdominal pain,
bloating) confirmed in the e-diary with at least 50% compliance of entry for at least
14 days during the screening period.
4. Male subjects who are post-pubertal must be sterile (surgically or otherwise) for at
least 6 months or are using single barrier contraception during the duration of the
trial and up until 1 month after the last dose AB-2004.
OR
Female subjects that are not lactating and have a negative pregnancy test at the
Screening and who are surgically sterile for at least 6 months or who agree to use
double-barrier contraception, an intrauterine device, or an oral contraceptive over the
duration of the trial and at least 4 weeks after the last dose of AB-2004
Minimum age
12 Years
Maximum age
17 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Participants must not meet any exclusion criteria (and meet all inclusion criteria) to be enrolled in the study. Following are the key Exclusion Criteria -
1. History of inflammatory bowel disease, bowel obstruction, diverticulosis or colon
polyps.
2. Oral, injected, inhaled antibiotic within 30 days prior to Screening
3. Currently taking a controlled or extended-release medication
4. History of significant gastric or intestinal surgery (excluding appendectomy).

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
Parallel
Other design features
Phase
Phase 1 / Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
No formal statistical testing of safety variables will be performed. Descriptive statistics and
frequency analysis (percentage of subjects) will be used.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
25/03/2019
Actual
18/04/2019
Date of last participant enrolment
Anticipated
20/12/2019
Actual
Date of last data collection
Anticipated
21/03/2020
Actual
Sample size
Target
35
Accrual to date
24
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD
Recruitment hospital [1] 13255 0
Queensland Children's Hospital - South Brisbane
Recruitment postcode(s) [1] 25815 0
4101 - South Brisbane
Recruitment outside Australia
Country [1] 21310 0
New Zealand
State/province [1] 21310 0
Auckland

Funding & Sponsors
Funding source category [1] 299489 0
Commercial sector/Industry
Name [1] 299489 0
Axial Biotherapeutics Australia Pty Ltd.
Country [1] 299489 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Axial Biotherapeutics Australia Pty Ltd.
Address
ACN 623 947 599 of Level 6,
360 Queen Street, Brisbane QLD 4000
Australia
Country
Australia
Secondary sponsor category [1] 298815 0
None
Name [1] 298815 0
Address [1] 298815 0
Country [1] 298815 0
Other collaborator category [1] 280114 0
Commercial sector/Industry
Name [1] 280114 0
Novotech (Australia) Pty Limited
Address [1] 280114 0
Level 2, 235 Pyrmont Street, Pyrmont NSW 2009 Australia
Country [1] 280114 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300395 0
Bellberry HREC
Ethics committee address [1] 300395 0
Ethics committee country [1] 300395 0
Australia
Date submitted for ethics approval [1] 300395 0
10/05/2018
Approval date [1] 300395 0
11/12/2018
Ethics approval number [1] 300395 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 83518 0
Prof Adam Guastella
Address 83518 0
The University of Sydney, Brain & Mind Centre
The University of Sydney,
Brain & Mind Centre, 94 Mallett
St, Camperdown NSW 2050
Country 83518 0
Australia
Phone 83518 0
+61 2 9351 0539
Fax 83518 0
Email 83518 0
adam.guastella@sydney.edu.au
Contact person for public queries
Name 83519 0
Adam Guastella
Address 83519 0
The University of Sydney, Brain & Mind Centre
The University of Sydney,
Brain & Mind Centre, 94 Mallett
St, Camperdown NSW 2050
Country 83519 0
Australia
Phone 83519 0
+61 2 9351 0539
Fax 83519 0
Email 83519 0
adam.guastella@sydney.edu.au
Contact person for scientific queries
Name 83520 0
Adam Guastella
Address 83520 0
The University of Sydney, Brain & Mind Centre
The University of Sydney,
Brain & Mind Centre, 94 Mallett
St, Camperdown NSW 2050
Country 83520 0
Australia
Phone 83520 0
+61 2 9351 0539
Fax 83520 0
Email 83520 0
adam.guastella@sydney.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?



Results publications and other study-related documents

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

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseSafety and target engagement of an oral small-molecule sequestrant in adolescents with autism spectrum disorder: an open-label phase 1b/2a trial.2022https://dx.doi.org/10.1038/s41591-022-01683-9
N.B. These documents automatically identified may not have been verified by the study sponsor.