Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619001378112
Ethics application status
Approved
Date submitted
26/08/2019
Date registered
9/10/2019
Date last updated
7/10/2021
Date data sharing statement initially provided
9/10/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase I clinical study to evaluate safety, tolerability and biological activity of platelet-derived extracellular vesicles on wound healing in healthy adults
Scientific title
A Prospective open-Label, single dose proof of concept study to Evaluate the safety, tolerability and biological activity of platelet-derived extracellular vesicles, on the augmentation of wound healing rate and effect on scar formation following skin punch biopsy in healthy volunteer adults
Secondary ID [1] 299068 0
None
Universal Trial Number (UTN)
Trial acronym
PLEXOVAL
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Wound healing 314095 0
Condition category
Condition code
Skin 312473 312473 0 0
Normal skin development and function

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The active drug is Plexaris (formulation of platelet-derived extracellular vesicles). One to two weeks prior to drug administration, participants will be required to undergo a procedure to extract a sample of their own platelets, which will then be processed into the Plexaris drug product. The drug product will be patient-specific (autologous) for this study.

Each patient receives a punch biopsy in the upper underside of both their arms to form a small wound. The 0.3 mg/mL Plexaris drug product is administered by intradermal injection in two locations adjacent to the punch biopsy wound in the non-dominant arm. The placebo formulation is administered by intradermal injection in two locations adjacent to the punch biopsy wound in the dominant arm.
The same procedure is followed for Cohort 1 and Cohort 2, however Cohort 2 will receive a further punch biopsy seven days after the initial biopsy. This will partially intersect the original biopsy to enable the partially healed wound tissue to be extracted for analysis.
Intervention code [1] 315335 0
Treatment: Drugs
Comparator / control treatment
A matched placebo formulation that does not contain extracellular vesicles will be administered to a second matched wound site in the dominant arm of each participant. The placebo contains sucrose, polysorbate 20, sodium chloride and L-Histidine.
Control group
Placebo

Outcomes
Primary outcome [1] 321116 0
Record the incidence and severity of adverse drug reactions that are considered to have a causal relationship with PLEXARIS administration. Potential reactions include injection site reactions, erythema, pruritus. Clinicians will make observations regarding adverse events at study visits and will ask participants to recall the occurrence of adverse events that may have occurred between study visits.
Timepoint [1] 321116 0
Day 0, 3, 7, 10, 14, 21, 28 and 42 (Cohort 1) and Day 0, 3, 7, 30 (Cohort 2).
Secondary outcome [1] 374040 0
Determination of time to wound closure of skin biopsy wound following PLEXARIS administration relative to control biopsy wound in Cohort 1 by determining the number of days taken for the wound to close. Wound size will be measured at each visit using a ruler.

Timepoint [1] 374040 0
Day 0, 3, 7, 10, 14, 21, 28 and 42
Secondary outcome [2] 374043 0
Compare the presence of scarring by clinical observation of the presence of hypertrophic scarring, hypotrophic scarring and redness between PLEXARIS treated and control wounds at Day 42 in Cohort 1 (composite outcome)
Timepoint [2] 374043 0
Day 42
Secondary outcome [3] 374045 0
Compare the wound characteristics between PLEXARIS treated and control wounds up to Day 42 in Cohort 1 by clinical observation of presence of exudate, fibrin, granulation, wound margin, increase in wound temperature, presence of pus or odour and peri-wound odema (composite outcome)
Timepoint [3] 374045 0
Day 0, 3, 7, 10, 14, 21, 28, 42

Eligibility
Key inclusion criteria
• Adult patients aged 18 – 45 years
• Able to read, understand and sign Participant Information and Consent Form
• Suitable health status to participate in the study, determined by non-clinically significant Laboratory profiles, medical history, vital signs, physical examination as deemed by the Principal Investigator.
• No history of cardiac disease.
• No active or chronic diseases/disorders, no history of hospitalization for illness within the six months prior to enrolment into study, and no major surgery within the 6 months
prior to enrolment into study
• Females must be non-pregnant or non-lactating in the last 12 months, postmenopausal for at least 1 year (as confirmed by follicle stimulating hormone [FSH]), or surgically sterile for at least 6 months prior to dosing.
• All male and females of childbearing potential must agree to use two forms of acceptable contraception from the time of signing informed consent until 30 days after study completion. Acceptable forms of contraception are: a nonhormonal
intrauterine device (IUD); contraceptive sponge; diaphragm; cervical cap; a male sexual partner who agrees to use a male condom; a sterile sexual partner; or complete abstinence. Hormonal contraceptives may not be used from the time of signing the informed consent until end of treatment period. Female Participants of childbearing potential must have a negative urine pregnancy test result at the screening visit and at
Visit 4 . Male Participants must use contraception or practice complete abstinence for 30 days after dosing and must not donate sperm during this time.
• Agreeing to maintain wound dressings as per study instructions

Additional inclusion criteria specific for the donation of platelets:
• Height no less than 168 cm and weight no less than 70 kg as determined at screening visit (Visit 0)
• Platelet count no less than 215,000 platelets/µL
Minimum age
18 Years
Maximum age
45 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
• History of any clinically important cardiac, endocrinologic, haematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, and renal, or other major disease, as determined by the Investigator
• Chronic inflammatory disease
• Chronic infectious disease
• History of keloid formation
• Concurrent administration of NSAIDs, Immunosuppressive agents, anticoagulation therapy or systemic corticosteroids therapy
• Acute disease state (e.g., nausea, vomiting, diarrhoea) within 7 days of Study Visit 1.
• No personal history of cardiac arrhythmia, epilepsy and no family or personal history of prolonged QT syndrome
• History of any clinically important severe allergic or anaphylactic reaction or known or suspected hypersensitivity to compounds similar to the investigational product. Use of any
investigational or prescription drug within 30 days of Study Visit 1.
• Participation in another clinical trial or administration of any investigational product or experimental treatment within 12 weeks or 5 half-lives (whichever is longer) preceding Study Visit 1.
Additional exclusion criteria specific for the donation of platelets:
• Acute disease state (e.g., nausea, vomiting, diarrhea) within 7 days of proposed apheresis date
• Dental treatments (i.e. cleaning, scaling, fillings, etc) or root canals in the preceding 7 days
• Positive serologic findings for human immunodeficiency virus (HIV) antibodies, hepatitis B surface antigen (HBsAg), and/or hepatitis C virus (HCV) antibodies.
• Positive serologic screening for HTLV (human T-lymphotropic virus) and syphilis
• Any other findings that the Investigator considers precludes the participant from taking part in the study.
• Veins that are not suitable for a large gauge needle used during apheresis

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)
N/A
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
N/A
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Each participant will receive a punch biopsy in their left and right arm. One wound will receive the active treatment, and one wound will receive the comparator (placebo) treatment.
Phase
Phase 1
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
The evaluation of safety will be based on the safety analysis set. The data collected will be
presented in listings and summary tables to give an overview of the safety findings. No
inferential statistical analysis of safety data is planned.

Descriptive statistics (n, mean, standard deviation, median, and range) for each clinical
assessments of wound diameter and Modified Hollander Wound Evaluation Score will be
presented by study part and available visit. Change from baseline values will also be
presented for each post-baseline measurement for the control and treated arms. Results will also be individually listed.

Descriptive statistics (n, mean, standard deviation, median, and range) will be presented for
data related to vital signs (i.e. blood pressure, pulse rate, respiration rate and temperature).
Change from baseline values will also be presented for each post-baseline measurement.
Vital signs results will also be individually listed.

Physical Exam will be summarised by visit in terms of n (%) of patients with
normal/abnormal results per body system and study part. Moreover, shift tables (from normal to abnormal and abnormal to normal) will be presented (when possible) for each postbaseline measurement. Physical examination results will also be individually listed.

Recruitment
Recruitment status
Stopped early
Data analysis
Data analysis is complete
Reason for early stopping/withdrawal
Participant recruitment difficulties
Date of first participant enrolment
Anticipated
21/10/2019
Actual
18/11/2019
Date of last participant enrolment
Anticipated
30/04/2021
Actual
10/03/2020
Date of last data collection
Anticipated
28/05/2021
Actual
10/03/2020
Sample size
Target
20
Accrual to date
Final
3
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 303599 0
Commercial sector/Industry
Name [1] 303599 0
Exopharm Ltd
Country [1] 303599 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Exopharm Ltd
Address
Level 17/31 Queen St,
Melbourne VIC 3000
Country
Australia
Secondary sponsor category [1] 303694 0
None
Name [1] 303694 0
Address [1] 303694 0
Country [1] 303694 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304128 0
Melbourne Health Human Research Ethics Committee
Ethics committee address [1] 304128 0
Ethics committee country [1] 304128 0
Australia
Date submitted for ethics approval [1] 304128 0
30/04/2019
Approval date [1] 304128 0
16/07/2019
Ethics approval number [1] 304128 0
HREC/52345/MH-2019
Ethics committee name [2] 304133 0
Australian Red Cross Blood Service Human Research Ethics Committee
Ethics committee address [2] 304133 0
Ethics committee country [2] 304133 0
Australia
Date submitted for ethics approval [2] 304133 0
Approval date [2] 304133 0
19/08/2019
Ethics approval number [2] 304133 0
2019#14

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

Contacts
Principal investigator
Name 95906 0
A/Prof Johannes Kern
Address 95906 0
Royal Melbourne Hospital
300 Grattan Street
Parkville VIC 3050
Australia
Country 95906 0
Australia
Phone 95906 0
+61 3 9342 4532
Fax 95906 0
Email 95906 0
[email protected]
Contact person for public queries
Name 95907 0
Gregor Lichtfuss
Address 95907 0
Exopharm Ltd
Level 17, 31 Queen Street
Melbourne VIC 3000
Australia
Country 95907 0
Australia
Phone 95907 0
+61 3 9111 0026
Fax 95907 0
Email 95907 0
[email protected]
Contact person for scientific queries
Name 95908 0
Gregor Lichtfuss
Address 95908 0
Exopharm Ltd
Level 17, 31 Queen Street
Melbourne VIC 3000
Australia
Country 95908 0
Australia
Phone 95908 0
+61 3 9111 0026
Fax 95908 0
Email 95908 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
SourceTitleYear of PublicationDOI
EmbaseThe therapeutic and commercial landscape of stem cell vesicles in regenerative dermatology.2023https://dx.doi.org/10.1016/j.jconrel.2022.12.025
N.B. These documents automatically identified may not have been verified by the study sponsor.