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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]

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

Condition category

Condition code

Human Genetics and Inherited Disorders

Other human genetics and inherited disorders

Mental Health

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]

Treatment: Drugs

Comparator / control treatment

No control group

Control group

Uncontrolled

Outcomes

Primary outcome [1]

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]

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]

Changes in measures of intestinal permeability as assessed in Urine Lactulose and Mannitol Test

Timepoint [1]

Monitored at Screening Visit, End of treatment(V5 day 57(+5)) and follow -up(V6 85(+5)).

Secondary outcome [2]

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]

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]

Changes in mood, as assessed by the Pediatric Anxiety Rating Scale (PARS) & Child and Adolescent Inventory 5 (CASI-5), Anxiety & Depression subscales

Timepoint [3]

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]

Changes in symptom severity assessments: Repetitive Behaviors Scale - Revised (RBS-R)

Timepoint [4]

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]

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]

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?

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

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

NSW,QLD

Recruitment hospital [1]

Queensland Children's Hospital - South Brisbane

Recruitment postcode(s) [1]

4101 - South Brisbane

Recruitment outside Australia

Country [1]

New Zealand

State/province [1]

Auckland

Funding & Sponsors

Funding source category [1]

Commercial sector/Industry

Name [1]

Axial Biotherapeutics Australia Pty Ltd.

Address [1]

ACN 623 947 599 of Level 6,
360 Queen Street, Brisbane QLD 4000
Australia

Country [1]

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]

None

Name [1]

Address [1]

Country [1]

Other collaborator category [1]

Commercial sector/Industry

Name [1]

Novotech (Australia) Pty Limited

Address [1]

Level 2, 235 Pyrmont Street, Pyrmont NSW 2009 Australia

Country [1]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Bellberry HREC

Ethics committee address [1]

129 Glen Osmond Rd, Eastwood SA 5063, Australia

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

10/05/2018

Approval date [1]

11/12/2018

Ethics approval number [1]

Summary

Brief summary

This is an open-label, outpatient, multiple ascending dose study of AB-2004 in approximately 35 adolescent subjects diagnosed with 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 behaviors and affect (particularly anxiety and irritability) and the measures of brain connectivity and white matter integrity.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Prof Adam Guastella

Address

The University of Sydney, Brain & Mind Centre
The University of Sydney,
Brain & Mind Centre, 94 Mallett
St, Camperdown NSW 2050

Country

Australia

Phone

+61 2 9351 0539

Fax

[email protected]

Contact person for public queries

Name

Adam Guastella

Address

The University of Sydney, Brain & Mind Centre
The University of Sydney,
Brain & Mind Centre, 94 Mallett
St, Camperdown NSW 2050

Country

Australia

Phone

+61 2 9351 0539

Fax

[email protected]

Contact person for scientific queries

Name

Adam Guastella

Address

The University of Sydney, Brain & Mind Centre
The University of Sydney,
Brain & Mind Centre, 94 Mallett
St, Camperdown NSW 2050

Country

Australia

Phone

+61 2 9351 0539

Fax

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

What supporting documents are/will be available?

Doc. No.	Type	Citation	Link	Email	Other Details	Attachment
613	Ethical approval				Not applicable	375115-(Uploaded-04-12-2018-16-43-23)-Study-related document.pdf
614	Ethical approval				Not Applicable	375115-(Uploaded-04-12-2018-16-45-40)-Study-related document.pdf

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Safety and target engagement of an oral small-molecule sequestrant in adolescents with autism spectrum disorder: an open-label phase 1b/2a trial.	2022	https://dx.doi.org/10.1038/s41591-022-01683-9

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Documents added manually

Documents added automatically