Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621001545853
Ethics application status
Approved
Date submitted
11/08/2021
Date registered
12/11/2021
Date last updated
12/11/2021
Date data sharing statement initially provided
12/11/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase 1c, Single Centre Study Investigating the Safety and Tolerability of a Lysyl Oxidase Inhibitor (PXS-6302) vs Placebo in the Amelioration of Established Scars.
Scientific title
A Phase 1c, Single Centre Study Investigating the Safety and Tolerability of a Lysyl Oxidase Inhibitor (PXS-6302) vs Placebo in the Amelioration of Established Scars.
Secondary ID [1] 305017 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record
Follow up study to ACTRN12621000322831

Health condition
Health condition(s) or problem(s) studied:
burns 323187 0
scarring 323188 0
Condition category
Condition code
Skin 320771 320771 0 0
Other skin conditions
Injuries and Accidents 321095 321095 0 0
Burns
Surgery 321096 321096 0 0
Other surgery

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The interventional product (IP) is a topical cream with a Lysl oxidase inhibitor that prevents collagen cross linking formation which leads to fibrotic tissue associated with scar formation.
The active agent lysyl oxidase inhibitor, an enzyme known as PXS-6302 has been formulated as an oil in water cream. Pre-filled 1 mL Luer lock syringes fitted with a cap will be provided. Three syringes will be provided per participant (equivalent to three month supply). Participants will receive multiples doses of PXS-6302, 4 mg (2.0%).

Participants will be sent home with this three month supply of either IP or placebo. The application of the cream will be onto the scar itself in via 1ml/10cm squared area. This will be achieved by one click of the syringe. Participants will be allocated to either intervention or placebo arm via alternating sequence.

PXS-6302 will be manufactured, packaged and labelled by Pharmaxis Ltd., in accordance with Good Manufacturing Principles for Medicinal Products for use in human clinical trials and will be provided with a certificate of analysis.
Intervention code [1] 321414 0
Treatment: Drugs
Comparator / control treatment
This study will use two arms; intervention and placebo. The application method remains identical for the intervention and placebo arms. Apply 1ml/10cmsquared area over the scar. Strategies engaged to monitor adherence include syringe return and participant self reporting. The placebo cream will be identical in formulation to the IP but without PXS-6302.
Control group
Placebo

Outcomes
Primary outcome [1] 328584 0
To investigate the safety and tolerability of multiple applications of PXS-6302 vs placebo in a target cohort. This will determined via the following:
Incidence and severity of adverse events (AE);
Incidence of serious adverse events (SAE) and suspected unexpected serious adverse reactions;
Clinically significant changes from baseline in:
Laboratory evaluations (hematology, chemistry)
Vital signs;
Physical examinations
Timepoint [1] 328584 0
Primary timepoints are Day 7, 21, 28. At 2 months and Day 90.
Secondary outcome [1] 399538 0
To determine the pharmacokinetics of PXS-6302 with multiple applications of a single dose we will investigate the following:
Blood samples will be centrifuged to generate plasma. Plasma concentrations of PXS-6302 will be determined using validated HPLC-MS/MS assays following solid-phase extraction of the plasma sample.
Activity of lysyl oxidases in tissue treated with PXS-6302 via:
Pharmacokinetic parameters including:
Area under the serum PXS-6302 concentration curve (AUC);
Peak plasma concentration (Cmax);
Time to peak plasma concentration (Tmax);
Elimination half-life (t1/2);
Clearance (Cl);
Volume of distribution (Vz)
Timepoint [1] 399538 0
Secondary timepoints are as follows:

Day 1: Pre-dose (within 30 minutes prior to dosing)
Day 7: Pre day 7 dose (within 30 minutes prior to dosing)
Day 21: Pre day 21 dose (within 30 minutes prior to dosing)
Day 28: Pre day 28 dose (within 30 minutes prior to dosing)
2 months Pre 2 month dose (within 30 minutes prior to dosing)
Day 90 24 hours after final dose
Secondary outcome [2] 399539 0
Skin punch biopsies (3 mm) will be performed for the evaluation of pharmacodynamic and biomarker activity to PXS-6302 including LOX/LOXL1 activity to demonstrate inhibition compared to pre-dose sample. This will be conducted as a composite secondary outcome.

Timepoint [2] 399539 0
Skin biopsies will be performed as follows:
Within 3 hours pre dose on Day 1 and 24 hours (± 30 minutes) post dose on Day 7, Day 28 and Day 90.

Eligibility
Key inclusion criteria
To be eligible for study entry subjects must satisfy all of the following criteria:

1. Male or female and aged between 18 and 60 years (inclusive) at the screening visit;
2. Body Mass Index (BMI) between 18.0 kg/m2 and 32.0 kg/m2 (inclusive) at the screening visit;
3. Have a scar duration between 1-5 years.
4. Adequate venous access in the left or right arm to allow collection of a number of blood samples;
5. A male subject is eligible to participate if he agrees to using one medically approved (i.e., mechanical or pharmacological) contraceptive measure and have their partners agree to an additional barrier method of contraception for the duration of the study and for 90 days after the last administration of study drug; Women of childbearing potential must use effective contraception. Adequate methods of contraception include use of oral contraceptives or Depo-Provera, with an additional barrier method (diaphragm with spermicidal gel or condoms with spermicide), double-barrier methods (diaphragm with spermicidal gel and condoms with spermicide), partner vasectomy, and total abstinence
6. Able to understand, give consent, and comply with all scheduled study visits, procedures and restrictions.
Minimum age
18 Years
Maximum age
60 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Subjects will be excluded from the study if one or more of the following criterion are applicable:

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 Investigator, would jeopardize the safety of the subject or impact the validity of the study results;

2. Current acute skin condition (eg: eczema, psoriasis, broken skin, wounds etc) or large tattoos or excess hair at the study drug application site. Normal hair coverage and small blemishes are acceptable at the discretion of the Investigator.

3. History of keloid scarring.

4. History of immediate hypersensitivity to any medication or currently suffers from clinically significant systemic allergic disease;

5. Presence of a recent musculoskeletal injury or currently healing fracture;

6. Have received or is anticipated to receive any prescription systemic or topical medication within 14 days prior to the start of dosing or within 5 half-lives of the study drug, whichever is greater, or use of any over-the-counter, complementary or alternative medicine 48 hours prior to the start of dosing (with the exception of paracetamol up to 2g per day, the use of intra-nasal and inhaled corticosteroids or antihistamines and vitamins);

7. At Investigator discretion if systolic blood pressure <90 or >140 mmHg, diastolic blood pressure <50 or >95 mmHg, and heart rate <40 or >100 bpm;

8. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), or bilirubin
>1.5 × upper limit of normal. Test may be repeated once at the discretion of the Investigator;

9. Hemoglobin, white blood cell (WBC), neutrophils, platelets < lower limit of normal. Test may be repeated once at the discretion of the Investigator;

10. Evidence of significant renal insufficiency, as indicated by an estimated creatinine clearance using the Cockcroft-Gault formula < 80 mL/min at Screening;

11. Receipt of blood, or loss or donation of 450 mL or more of blood within 90 days or plasma donation within 14 days before the first dose administration;

12. Have received an experimental therapy within 30 days or 5 half-lives of the study drug, whichever is longer, prior to dosing;

13. Systemic infection other than common cold in the week prior to dosing.

14. Pregnant females.


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
Baseline demographics, descriptive statistics and tests for association and differences between intervention and placebo will be used.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
13/12/2021
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
50
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 20215 0
Fiona Stanley Hospital - Murdoch
Recruitment postcode(s) [1] 34945 0
6150 - Murdoch

Funding & Sponsors
Funding source category [1] 309405 0
Commercial sector/Industry
Name [1] 309405 0
Pharmaxis Ltd
Country [1] 309405 0
Australia
Primary sponsor type
University
Name
University of Western Australia
Address
35 Hackett Drive,
Crawley, Western Australia 6008
Country
Australia
Secondary sponsor category [1] 310375 0
None
Name [1] 310375 0
Address [1] 310375 0
Country [1] 310375 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309211 0
South Metropolitan Health Service Human Research Ethics Committee
Ethics committee address [1] 309211 0
Ethics committee country [1] 309211 0
Australia
Date submitted for ethics approval [1] 309211 0
26/08/2021
Approval date [1] 309211 0
19/10/2021
Ethics approval number [1] 309211 0

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

Contacts
Principal investigator
Name 113358 0
Dr Kylie Sandy-Hodgetts
Address 113358 0
School of Biomedical Sciences,
University of Western Australia
35 Hackett Drive, Crawley
Western Australia 6009
Country 113358 0
Australia
Phone 113358 0
+61435436747
Fax 113358 0
Email 113358 0
[email protected]
Contact person for public queries
Name 113359 0
Kylie Sandy-Hodgetts
Address 113359 0
School of Biomedical Sciences,
University of Western Australia
35 Hackett Drive, Crawley
Western Australia 6009
Country 113359 0
Australia
Phone 113359 0
+61435436747
Fax 113359 0
Email 113359 0
[email protected]
Contact person for scientific queries
Name 113360 0
Mark Fear
Address 113360 0
School of Biomedical Sciences,
University of Western Australia
35 Hackett Drive, 'Crawley
Western Australia 6009
Country 113360 0
Australia
Phone 113360 0
+61 411355944
Fax 113360 0
Email 113360 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
Participant confidentiality.


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.