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Trial registered on ANZCTR


Registration number
ACTRN12618001341213
Ethics application status
Approved
Date submitted
3/08/2018
Date registered
9/08/2018
Date last updated
10/12/2018
Date data sharing statement initially provided
10/12/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
A 15-Day, Single-blind, Placebo Controlled Food Safety and Tolerability Study of AXA3359 in Adult Subjects with Mild Traumatic Brain Injury (mTBI)
Scientific title
A 15-Day, Single-blind, Placebo Controlled Food Safety and Tolerability Study of AXA3359 in Adult Subjects with Mild Traumatic Brain Injury (mTBI)
Secondary ID [1] 295355 0
AXA3359-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Otherwise healthy individuals with mild Traumatic Brain Injury 308574 0
Concussion 308575 0
Condition category
Condition code
Neurological 307529 307529 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will be randomised to receive either 51.3g of active food product (AXA3359) or matched placebo per administration at a 2:1 ratio respectively; a total of 16 administrations over 8 Days. The amount of study product per administration may be reduced based on ongoing safety data. AXA3359/ placebo will be dissolved in 350 ml water for consumption. Participants will receive their first administration of study product within 24hrs of a concussion/ mild Traumatic Brain Injury at the study centre. The 2nd administration will then be 1-3 hours after the first at the study centre. Participants will then be sent home with sufficient study product to self administer for their 3rd administration on Day 1 either before dinner or at bedtime whichever is sooner; and twice daily, before breakfast and dinner, on Days 2 -7. On Day 8 participants will return to the study centre and will received a single administration of study product before breakfast.
Adherence will be monitored via study product accountability by study personnel, and by review of the participant diary by study personnel in person with the participant on Day 8. Adherence will also be discussed with the participant either at the study centre or by phone on Days 2, 3, 4, 5, and 7.
Blood samples will be collected on Day 1 and on Day 8 to assess blood levels of study product to assist with adherence.
Intervention code [1] 301677 0
Treatment: Other
Comparator / control treatment
A match placebo group will be the control group consisting of maltodextrin powder and flavourings to match the active study product.
Control group
Placebo

Outcomes
Primary outcome [1] 306525 0
Safety and tolerability
Timepoint [1] 306525 0
These will be determined by reported adverse events (AEs), physical and neurological examinations (including EEG, neurocognitive tests, SCAT5), clinical laboratory tests, vital sign measurements, and ECGs and blood biomarkers of neural injury. Safety will be assessed on an ongoing basis including at all scheduled study visits (Days 1, 2, 3, 5, 8, 11, 15) and phone calls (Days 4, 7, 10, 14) from consent to the participants last study visit on Day 15. All AEs will be followed to resolution or until stabilised.
Tolerability will also be assessed using information in the product administration diaries, from which either amount and/or frequency may be reduced, if needed.
Secondary outcome [1] 348783 0
Pharmacokinetic parameters including AUC0-t, Cmax, and Tmax will be assessed
Timepoint [1] 348783 0
Pharmacokinetic blood samples will be collected at baseline, before study product administration on Day 8 (pre-administration, and then 30 mins, 1 hr, 1.5 hrs, 2 hrs, 3 hrs, 4 hrs and 5 hrs post administration).

Eligibility
Key inclusion criteria
1. Males or females aged 18-35 years (inclusive)
2. Body Mass Index < 32 kg/m2
3. Confirmed medical diagnosis of concussion/mTBI from a study investigator within 24 hours or less of the injury event.
4. Otherwise in generally good health, and be nonsmokers and abstain from any alcohol use for the duration of the study.
6. A Brain Function Index (BFI) of <= 40 percentile
Minimum age
18 Years
Maximum age
35 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Individuals with any clinically significant or unstable medical conditions, other than mTBI, requiring acute intervention.
2. Individuals with a concussion or a prior concussion or hospitalization for a head injury within 60 days
4. Any head trauma that is considered “moderate” or “severe” by the study investigator as measured by Glasgow Coma Scale (GCS) score of <13 within 24 hours of injury.
15. Receipt of an investigational drug or any investigational dietary supplement/food product (including, but not limited to creatine, Lacetyl carnitine, N-acetyl cysteine, any amino acids, protein drinks, fish oils, etc.), or participation in a trial of an investigational device within 1 month (or 5 half-lives), whichever is longer, before Screening.

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)
Once the study investigator confirms that the participant is eligible for the trial, they will request that the participant is randomised to receive either active study product or matched placebo based on the randomisation schema provided by the sponsor. As this is a single blinded study, only participants will be blinded/ concealed from knowing their study product allocation. Both active and placebo study products are labelled in a manner which does not disclose to the participant their study product allocation, however is coded to enable study staff to know their allocation if required. Every effort will be made by the study staff and sponsor representatives to ensure the participant does not find out their allocation. The site specific allocation schema will be housed in an area not accessible by study participants to ensure concealment remains intact.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Every site will have a site-specific paper static randomisation schedule and participants will be randomised consecutively based on their enrollment number in blocks of 3 (2 active and 1 placebo control per block).
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint(s)
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
No data analysis planned
Reason for early stopping/withdrawal
Participant recruitment difficulties
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] 11279 0
The Alfred - Prahran
Recruitment postcode(s) [1] 23166 0
3004 - Prahran

Funding & Sponsors
Funding source category [1] 299947 0
Commercial sector/Industry
Name [1] 299947 0
Axcella Health Inc.
Address [1] 299947 0
840 Memorial Drive, 3rd Floor
Cambridge, MA 02139 USA
Country [1] 299947 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Axcella Health Inc.
Address
840 Memorial Drive, 3rd Floor
Cambridge, MA 02139 USA
Country
United States of America
Secondary sponsor category [1] 299323 0
Other
Name [1] 299323 0
The Florey Institute of Neuroscience and Mental Health trading as Neuroscience Trials Australia
Address [1] 299323 0
245 Burgundy Street, Heidelberg VIC 3084
Country [1] 299323 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300813 0
St Vincent's Hospital Melbourne Human Research Ethics Committee
Ethics committee address [1] 300813 0
St Vincent's Hospital Melbourne
40 Victoria Pde, Fitzroy, VIC, 3065
Ethics committee country [1] 300813 0
Australia
Date submitted for ethics approval [1] 300813 0
20/03/2018
Approval date [1] 300813 0
21/05/2018
Ethics approval number [1] 300813 0
HREC/18/SVHM/123

Summary
Brief summary
This is a 15-day, single-blind, placebo-controlled study intended to assess the safety and tolerability as well as pharmacokinetics of the food product, AXA3359 administered over 8 days in adult participants with mild traumatic brain injury (mTBI). Up to 30 participants will be enrolled and randomised to receive either AXA3359 or matched placebo at a 2:1 ratio respectively. Participants will receive their first administration of study product within 24 hours of a mTBI and will receive a total of 3 study product administrations on the first study day regardless of food. On Days 2-7 participants will received study product twice daily 30 minutes before breakfast and dinner respectively. On Day 8, participants will have blood samples collected before and after administration to assess the pharmacokinetic properties of AXA3359. Safety follow up will extend to 15 days post first dose.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 84898 0
Prof Terence O’Brien
Address 84898 0
The Alfred Hospital 55 Commercial Rd, Melbourne, VIC, 3004
Country 84898 0
Australia
Phone 84898 0
+61 3 9076 2029
Fax 84898 0
Email 84898 0
te.obrien@alfred.org.au
Contact person for public queries
Name 84899 0
Dr Tristan Iseli
Address 84899 0
Neuroscience Trials Australia
245 Burgundy St, Heidelberg, VIC, 3084
Country 84899 0
Australia
Phone 84899 0
+61 3 9035 7195
Fax 84899 0
Email 84899 0
tristan.iseli@florey.edu.au
Contact person for scientific queries
Name 84900 0
Prof Terence O’Brien
Address 84900 0
The Alfred Hospital 55 Commercial Rd, Melbourne, VIC, 3004
Country 84900 0
Australia
Phone 84900 0
+61 3 9076 2029
Fax 84900 0
Email 84900 0
te.obrien@alfred.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Insufficient data to be meaningful with only 1 recruited
What supporting documents are/will be available?
No other documents available
Summary results
No Results