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Trial registered on ANZCTR


Registration number
ACTRN12623001071617
Ethics application status
Approved
Date submitted
12/09/2023
Date registered
6/10/2023
Date last updated
6/10/2023
Date data sharing statement initially provided
6/10/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Investigating targEting LysyL oxIdase tO ameliorate scarring in burn Trauma
Scientific title
Investigating Safety and Preliminary Efficacy of TargEting LysyL oxIdase tO ameliorate scarring in burn Trauma
Secondary ID [1] 308959 0
Nil known
Universal Trial Number (UTN)
U1111-1290-8614
Trial acronym
ELLIOT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
burn injury 329624 0
Condition category
Condition code
Skin 326548 326548 0 0
Other skin conditions
Injuries and Accidents 328262 328262 0 0
Burns

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will receive PXS-5505 at a dose of 200mg twice daily in oral capsules for 26 weeks. PXS-5505 will be dispensed at baseline (start of treatment), and at 4, and 12 week visits after the start of treatment. Unused capsules will be returned at 4, 12 and 26 week visits in order to assess compliance. Each time treatment is dispensed, subjects will be provided with a diary containing dosing instructions where they can log each dose taken and any issues.


Intervention code [1] 325829 0
Treatment: Drugs
Comparator / control treatment
Control group will receive placebo in oral capsules twice daily for 26 weeks. Hard capsules containing inactive ingredients of mannitol and magnesium stearate identical in appearance to the PXS-5505 capsules. Placebo will be dispensed at baseline (start of treatment), and at 4, and 12 week visits after the start of treatment. Unused capsules will be returned at 4, 12 and 26 week visits in order to assess compliance. Each time treatment is dispensed, subjects will be provided with a diary containing dosing instructions where they can log each dose taken and any issues.
Control group
Placebo

Outcomes
Primary outcome [1] 334387 0
Adverse events (incidence and severity of adverse events and serious adverse events)

At each study visit the investigator is responsible for recording all adverse events i,e. any untoward medical occurrence whether or not it is considered to have a causal relationship with treatment.

The severity of adverse events will be assessed by the investigator using CTCAE V5.0 criteria.

An event will be categorized as serious if; it results in death; is life threatening, requires hospitalization (or prolongation of existing hospitalization); results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or is a medically important event or reaction.

Adverse events will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) and grouped by system organ class and preferred term when summarized.
Timepoint [1] 334387 0
All adverse events from start of treatment to 26 weeks, and for 4 weeks after discontinuation of treatment will be captured. Investigators will assess the occurrence of adverse events at each visit (at start of treatment and 1 week, 4 week, 12 weeks and 26 weeks after start of treatment, and 4 weeks after discontinuation.)
Primary outcome [2] 335637 0
Clinical laboratory tests, vital signs and physical examinations (this will be assessed as a composite outcome to assess overall tolerability).

A peripheral blood sample will be taken and the following clinical laboratory tests performed: full blood count, beta-2 microglobulin, serum free light chains (Kappa/Lambda ratio), immunoelectrophoresis, electrolytes including calcium, magnesium and phosphate, creatinine, lactic dehydrogenase, troponin 1; Liver function: total & direct bilirubin, albumin, total protein, alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase and alkaline phosphatase; Kidney function: serum creatinine, blood urea nitrogen, estimated glomerular filtration rate.

Vital signs measured will be oral temperature (measured using digital thermometer), pulse rate (pulse oximeter), respiratory rate (manual count) and blood pressure (pulse and blood pressure to be measured after subject has been resting comfortably for at least 5 minutes in a semi-supine position using a sphygmomanometer.)

A full physical examination will be performed at screening and will include examination of the following: general appearance, head, ears, eyes, nose, throat, neck (including thyroid), skin (including dosing area), cardiovascular system, respiratory system, gastrointestinal system, musculoskeletal system, lymph nodes and nervous system.

An abbreviated physical examination will be performed at subsequent visits and will include, at a minimum, assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen).
Timepoint [2] 335637 0
Baseline (start of treatment) and 1, 4, 12 and 26 weeks after the start of treatment.
Primary outcome [3] 335638 0
Plasma concentration of PXS-5505, measured in blood sample.
Timepoint [3] 335638 0
Baseline (start of treatment), and 4, 12, 26 weeks (prior to first study drug dose of the day) after start of treatment
Secondary outcome [1] 420469 0
Patient and Observer Scar Assessment Scale (POSAS) v3.0,
The POSAS measures scar quality in all types of scars by evaluating visual (e.g. color), tactile (e.g. pliability) and sensory (e.g. itch) characteristics of the scar from the perspective of the observer and patients.
Timepoint [1] 420469 0
Baseline (start of treatment), and 4, 12 and 26 weeks after start of treatment and 4 weeks after treatment discontinuation.
Secondary outcome [2] 420470 0
Modified vancouver scar score (VSS). This assesses the height, pliability, pigmentation and vascularity of the scar.
Timepoint [2] 420470 0
Baseline (start of treatment), and 4, 12 and 26 weeks after start of treatment and 4 weeks after treatment discontinuation.
Secondary outcome [3] 420471 0
3D volumetric scan of scar
Timepoint [3] 420471 0
Baseline (start of treatment), and 4, 12 and 26 weeks after start of treatment and 4 weeks after treatment discontinuation.
Secondary outcome [4] 420472 0
Scar thickness using ultrasound
Timepoint [4] 420472 0
Baseline (start of treatment), and 4, 12 and 26 weeks after start of treatment and 4 weeks after treatment discontinuation.
Secondary outcome [5] 420473 0
Scar collagen density using ultrasound
Timepoint [5] 420473 0
Baseline (start of treatment), and 4, 12 and 26 weeks after start of treatment and 4 weeks after treatment discontinuation.
Secondary outcome [6] 425017 0
Scar elasticity (stiffness) using ultrasound based shear wave elastography
Timepoint [6] 425017 0
Baseline (start of treatment) and 1,4,12 and 26 weeks after start of treatment, and 4 weeks after treatment discontinuation.
Secondary outcome [7] 425022 0
Dermal vascular flow using ultrasound based Colour Doppler imaging
Timepoint [7] 425022 0
Baseline (start of treatment) and 1,4,12 and 26 weeks after start of treatment, and 4 weeks after treatment discontinuation
Secondary outcome [8] 425023 0
Oedema of the scar measured by bioimpedance spectroscopy (BIS)
Timepoint [8] 425023 0
Baseline (start of treatment) and 1,4,12 and 26 weeks after start of treatment, and 4 weeks after treatment discontinuation
Secondary outcome [9] 425024 0
Scar rating based on assessments from multiple raters of primary injury site photos (using a scale designed specifically for this study).
Timepoint [9] 425024 0
Baseline (start of treatment) and 1,4,12 and 26 weeks after start of treatment, and 4 weeks after treatment discontinuation
Secondary outcome [10] 425025 0
Use of other scar treatments (laser, pressure garments, occupational therapy (OT) sessions). To be assessed using a study specific data collection form.
Timepoint [10] 425025 0
All other scar treatments from start of treatment to 26 weeks, and for 4 weeks after discontinuation of treatment will be captured. Investigators will assess the other treatments used at screening at then those used since the last visit at each subsequent visit (baseline (start of treatment), 1 week, 4 week, 12 weeks and 26 weeks after start of treatment, and 4 weeks after discontinuation.)
Secondary outcome [11] 425026 0
Pharmacodynamic endpoints including lysyl oxidase (LOX) inhibition in peripheral blood samples (secondary outcome) and other biomarkers measured in blood, serum and skin biopsy samples (exploratory outcomes).
Timepoint [11] 425026 0
Baseline (start of treatment), and 4, 12, 26 weeks (prior to first study drug dose of the day) after start of treatment
Secondary outcome [12] 426962 0
Scar oedema using ultrasound
Timepoint [12] 426962 0
Baseline (start of treatment) and 1,4,12 and 26 weeks after start of treatment, and 4 weeks after treatment discontinuation
Secondary outcome [13] 426965 0
Electrical properties of the scar measured by bioimpedance spectroscopy (BIS)
Timepoint [13] 426965 0
Baseline (start of treatment) and 1,4,12 and 26 weeks after start of treatment, and 4 weeks after treatment discontinuation.

Eligibility
Key inclusion criteria
1. Aged between 21 and 60 years (inclusive).
2. Acute burn injury of >=5% and <=15% total body surface area (TBSA) requiring treatment with a split-thickness skin graft
3. Agree to use of adequate contraception if participant/partner of childbearing age.
4. Have given written informed consent to participate in this study in accordance with local regulations.
5. Able to understand, give consent, and comply with all scheduled study visits, procedures and restrictions.
Minimum age
21 Years
Maximum age
60 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Clinically significant gastrointestinal, renal, hepatic, neurologic, hematologic, endocrine, oncologic, pulmonary, immunologic, psychiatric, skin, or cardiovascular disease or any other condition, that, in the opinion of the Principal Investigator, would jeopardize the safety of the subject or impact the validity of the study results.
2. History of immediate hypersensitivity to any medication or currently suffers from clinically significant systemic allergic disease.
3. Alanine aminotransferase (ALT) and/or), aspartate aminotransferase (AST) >3.0 x), or bilirubin>2.5 × upper limit of normal (ULN) or direct bilirubin >1.5 ULN.).
4. Evidence of significant renal insufficiency, as indicated by an estimated creatinine clearance using the Cockcroft-Gault formula of less than 50 mL/min at Screening.
5. Have participated in a clinical trial or have received an experimental therapy within 30 days or 5 half-lives of the drug, whichever is longer, prior to dosing.
6. Active systemic infection
7. History of aneurysm

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. Eligible patients will be allocated to the next randomisation number in the sequence. Study medication is labelled with this randomisation number only and the specific treatment is not identified.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Block randomisation, 2:1 randomisation PXS5505:placebo
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis
The sample size for this study is 60 subjects, randomised 2:1 to PXS-5505 and placebo, to be treated with at least one dose of study medication. With this sample size and an assumed drop-out rate of up to 20% across the 26 week treatment period at least 48 subjects should complete the study. As this is an early phase study with a primary objective of safety, the sample size has primarily been selected to provide adequate information on the safety profile in this population to proceed to further studies. No formal sample size calculation was performed.

In general, data will be summarized using descriptive statistics (mean, median, standard deviation, minimum and maximum) or frequency counts and percentages, as appropriate to the type of data.

Preliminary efficacy measures will be summarised by treatment group and compared between treatment groups using t-tests or non-parametric tests as appropriate. The impact of baseline or injury characteristics on preliminary efficacy endpoints may be explored via exploratory modelling and/or analysis in relevant subgroups if the subject numbers allow. Information on other scar treatments during the study (e.g. the proportion of patients receiving laser treatment the timing of first laser treatment) may also be summarised and compared between groups if subject numbers allow.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
6/11/2023
Actual
Date of last participant enrolment
Anticipated
23/12/2024
Actual
Date of last data collection
Anticipated
24/07/2025
Actual
Sample size
Target
60
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 25311 0
Fiona Stanley Hospital - Murdoch
Recruitment postcode(s) [1] 40064 0
6150 - Murdoch

Funding & Sponsors
Funding source category [1] 313172 0
Commercial sector/Industry
Name [1] 313172 0
Pharmaxis Ltd
Country [1] 313172 0
Australia
Primary sponsor type
University
Name
university of western australia
Address
35 Stirling HighwayCrawleyWA 6009
Country
Australia
Secondary sponsor category [1] 315373 0
None
Name [1] 315373 0
Address [1] 315373 0
Country [1] 315373 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312413 0
South Metropolitan Health Service HREC
Ethics committee address [1] 312413 0
Ethics committee country [1] 312413 0
Australia
Date submitted for ethics approval [1] 312413 0
22/02/2023
Approval date [1] 312413 0
03/04/2023
Ethics approval number [1] 312413 0
RGS0000005959

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

Contacts
Principal investigator
Name 124570 0
Dr Mark Fear
Address 124570 0
Burn injury research unitHarry Perkins institute lvl 56 Verdun streetNedlandsWA 6009
Country 124570 0
Australia
Phone 124570 0
+61 864888133
Fax 124570 0
Email 124570 0
[email protected]
Contact person for public queries
Name 124571 0
Mark Fear
Address 124571 0
Burn injury research unitHarry Perkins institute lvl 56 Verdun streetNedlandsWA 6009
Country 124571 0
Australia
Phone 124571 0
+61 864888133
Fax 124571 0
Email 124571 0
[email protected]
Contact person for scientific queries
Name 124572 0
Mark Fear
Address 124572 0
Burn injury research unitHarry Perkins institute lvl 56 Verdun streetNedlandsWA 6009
Country 124572 0
Australia
Phone 124572 0
+61 864888133
Fax 124572 0
Email 124572 0
[email protected]

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?

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.