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Trial registered on ANZCTR


Registration number
ACTRN12624000310561
Ethics application status
Approved
Date submitted
8/01/2024
Date registered
22/03/2024
Date last updated
10/11/2024
Date data sharing statement initially provided
22/03/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase 1, Open Label, First in Human (FIH) Study Investigating Photodynamic Therapy (PDT) with INV043 0.5% Ointment in Adults with Non-melanoma Skin Cancers
Scientific title
A Phase 1, Open Label, First in Human (FIH) Study Investigating Photodynamic Therapy (PDT) with INV043 0.5% Ointment in Adults with Non-melanoma Skin Cancers
Secondary ID [1] 311274 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non melanoma skin cancer 332512 0
Condition category
Condition code
Cancer 329196 329196 0 0
Non melanoma skin cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a Phase 1, Open Label, First in Human (FIH) Study Investigating Photodynamic Therapy (PDT) with INV043 0.5% Ointment in Adults with Non- melanoma Skin Cancers consisting of 2 parts:

• Part 1: Light dose escalation (fixed Dose Light Interval [DLI])
• Part 2 (optional dose escalation): DLI optimisation

A 3+3 dose escalation design will be utilized to guide light dose escalation in Part 1 according to the table below.

An accelerated titration design will be utilised to guide dose escalation in Part 2. The design will enrol a minimum of one participant per light dose level until 1 or more participant experiences 2 or more clinically significant, treatment-related > Grade 2 AE, following which dose escalation will follow a 3+3 design, starting with enrolment of a minimum 2 additional participants at that DLI.


Study periods will consist of:

• Screening Period: Screening period of up to 28 days
• Treatment Period: 14 days
• Follow-up Period: up to 12 months post-treatment
•Treatment with Ointment and Light Source occur on Day 1 of the Protocol schema and only administered once during the course of the study for the patient during both Part 1 and 2.

Participants who did not achieve a complete response on the treated lesion following initial treatment with INV043 PDT may undergo a repeat treatment on the same lesion following discussion and approval from study Sponsor. Retreated participants can be enrolled to any Part of the study depending on the part/cohort open at the time and provided the participant meets the retreatment eligibility criteria

Combination Investigational products:

INV043 Xingda XD660 LAS 1.1 (Photosensitiser)
INV043 is formulated as 5 mg per gram ointment, 0.5% w/w ointment for dermal application. Excipients include polyvinylpyrrolidone (PVP, as Kollidon 12 PF, same as povidone), dimethyl sulfoxide (DMSO), polyethylene glycol (PEG) 400 and PEG 1500.
INV043 is a phyllochlorin derivative comprising a chlorin molecule linked to a thioglucose moiety designed to facilitate the drug’s localisation into tumour cells.

INV043 is a dark blue-green flaky solid. It is essentially insoluble in water. It is soluble in ethanol and DMSO. The ointment is dark blue-green.

Container for ointment: INV043 0.5% w/w ointment (2 g) is filled into 2 mL USP Type 1 amber borosilicate glass vials capped with a removable bromobutyl stopper and crimped with a tear-off aluminium vial seal.

Dose/amount/volume of ointment per application
2 g (10 mg INV043 equivalent).

The weight of INV043 ointment applied will be recorded by weighing the container containing the ointment before and after topical application. INV043 ointment will be rubbed into the lesion and spread 2-3 mm into the surrounding skin. It will be removed with gauze just prior to illumination.

Light Source
Model: Xingda Laser Model PDT652, manufactured by Xingda Photoelectric Medical Equipment Co Ltd, Guilin, China
Wavelength: 660 nm; Intensity: 100 mW/cm2
Light Dose: (J/cm2) will be evaluated.

Current timing of the light source is as follows:
LD-2**- 36J/cm2 for 6 minutes
LD-1**- 50J/cm2 for 8 minutes and 20 seconds
LD1 - 75J/cm2 for 12 minutes and 30 seconds
LD2 (optional)* - 100j/cm2 for 16 minute and 40 seconds
LD3 (optional)* - 125J/cm2 for 20 minutes and 50 seconds
(Abbreviations: LD, Light Dose. Notes: *LD2, LD3 and LD4 may be explored if there is insufficient clinical activity observed in LD1.
** If required, lower dose levels will be explored to determine the optimal biological dose in LD-1 and LD-2)

Participant Population:

Part 1 and Part 2: cutaneous squamous cell carcinoma (cSCC)
Other NMSCs may be approved on a case-by-case basis by Sponsor if deemed to be in the participant’s best interest by PI judgment, and unlikely to put participant at a higher risk of treatment-related toxicity and/or interfere with the integrity of study outcome.

Part 2 (optional): Dose-light interval (DLI) Optimisation
An accelerated titration design will be utilised to guide dose escalation in Part 2. The design will enrol a minimum of one participant per light dose level until 1 or more participant experiences 2 or more clinically significant, treatment-related > Grade 2 AE, following which dose escalation will follow a 3+3 design, starting with enrolment of a minimum 2 additional participants at that DLI. The table below summarises the DLIs to be investigated.

DLI -2 5 minutes
DLI -1 10 minutes
DLI 1 30 minutes
DLI 2 1 hour
DLI 3 2 hours

Its Anticipated after each cohort completed the next cohort would commence approx 2- weeks after the conclusion of the previous cohort to allow for review of the Last Patient Last visit and Data safety meeting to occur and data reviewed.


The intervention would be provided at Veracity Clinical Research Institute in Australia by a qualified dermatologist (the principal investigator)
Intervention code [1] 327725 0
Treatment: Devices
Intervention code [2] 327724 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 337031 0
To characterize the safety and tolerability of PDT with INV043 in participants with nonmelanoma skin cancers and Incidence and nature of dose limiting toxicities (DLTs)


Timepoint [1] 337031 0
Day 1, Day 2, Day 8, Day 15 and every 3 month follow up through 1 year post-intervention commencement
Primary outcome [2] 337033 0
Incidence, nature and severity of adverse events (AEs) and serious adverse events (SAEs), changes in laboratory parameters, vital signs and ECG results
Timepoint [2] 337033 0
Day 1, Day 2, Day 8, Day 15 and every 3 month follow up through 1 year post-intervention commencement.
Primary outcome [3] 337032 0
Incidence and nature of dose limiting toxicities (DLTs)
Timepoint [3] 337032 0
Baseline (pre-intervention), Day 1, Day 2, Day 8, Day 15 and every 3 month follow up through 1 year post-intervention commencement
Secondary outcome [1] 432588 0
Progression Free Survival
Timepoint [1] 432588 0
6 months and 1 year post-intervention commencement
Secondary outcome [2] 430438 0
Objectives response rates (ORR) as assessed by RECIST V1.1
Timepoint [2] 430438 0
6 months and 1 year post-intervention commencement
Secondary outcome [3] 430439 0
Disease control rate, as defined by the proportion of participants with ongoing complete response
Timepoint [3] 430439 0
6 months and 12 months post treatment

Eligibility
Key inclusion criteria
Inclusion Criteria
1. Participant is capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form and is willing and able to return for all study visits and comply with all protocol requirements and procedures.
2. Participant is at least 18 years of age at the time of signing the informed consent.
3. ECOG performance status of 0 or 1.
4. Participants must have a life expectancy of greater then 12 months in the opinion of the Investigator.
5. Participants must have measurable disease based on RECIST 1.1.
6. Participants must have available archival tissue (at least 15 consecutive, unstained, formalin-fixed, paraffin embedded [FFPE] slides or 1 FFPE block) OR, alternatively, a fresh tumour biopsy sample. Participants without any archival tissue or fresh biopsy sample, or who refuse to provide archival tissue may be approved to enrol on a case-by-case basis in discussion with the Sponsor.
7. At least one primary, clinically diagnosed and histologically confirmed, Non-melanoma Skin Cancer lesion. Lesion must meet the following guidelines:
• Target lesion must be between 1.0 to 2.0 cm (inclusive) in longest diameter.
• Target lesion must be located on a body site easily accessible for topical application by the clinician, excluding the face and scalp area, genitals, perianal area, eyelids, ears.
• Target lesion must not be located in areas with significant confounding factors, such as tattoos or deformities, that may put participant at a higher risk of treatment-related toxicity and/or interfere with the integrity of study outcome.
• Participants with lesions that are greater then 2.0 cm and/or lesions located in the face, scalp, genitals, perianal, eyelids or ears, may be allowed on a case-by-case basis in discussion with study Sponsor if deemed unlikely to put participant at a higher risk of treatment-related toxicity and/or interfere with the integrity of study outcome.
8. For Part 1 and Part 2 (dose escalation cohorts), all participants must meet either of the following tumour-type criteria:
a. Non-metastatic cutaneous SCC.
b. Other NMSCs may be approved on a case-by-case basis by Sponsor if deemed to be in the participant’s best interest by PI judgment, and unlikely to put participant at a higher risk of treatment-related toxicity and/or interfere with the integrity of study outcome.
10. Participants must not require immediate surgical removal of treatment-targeted lesions. Targeted lesion must, in the assessment of the Investigator, be appropriate for study treatment over the anticipated duration of the study. Lesions that otherwise exhibit aggressive features by Investigator judgment should not be included and should be treated with appropriate standard of care.
11. The participant must be willing and able to abstain from using prohibited therapies, including the use of moisturizers or other topical non-medical treatments at the treatment site, for at least 24 hours before INV043 PDT and during study Treatment Period. .
12. Agree to abstain from sun exposure at the treatment site for the duration of the study to End of Treatment Visit (EOTV).
13. Women of childbearing potential (WOCBP) must have a negative beta-human chorionic gonadotropin (ß-hCG) test within 48 hours before the first dose of treatment administration and must not be breastfeeding.
14. WOCBP are defined as those who are not surgically sterile or post-menopausal. Female participants will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. Female participants less then 50 years old who meet the criteria for post-menopausal status without previous surgical sterilisation should be considered for further investigation with luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels to confirm serological post-menopausal status.
15. Women of childbearing potential (WOCBP) must agree to use highly effective contraceptive measures from Screening until 14 days after the last dose of study treatment. A female participant must also not be breast feeding and must have a negative pregnancy test (prior to start of dosing and for 14 days after the last dose of study treatment) if of childbearing potential or must have evidence of non-childbearing potential by fulfilling one of the criteria such as Female participants of childbearing potential are defined as those who are not surgically sterile or post-menopausal. Female participants will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. Female participants <50 years old who meet the criteria for post-menopausal status without previous surgical sterilisation should be considered for further investigation with LH and FSH levels to confirm serological post-menopausal status.
16. Male participants or participants who are able to father a child must agree to avoid impregnating a partner and to adhere to a highly effective method of contraception during the study and for 14 days after the last dose of study treatment. All male participants must agree to not donate sperm during the study and for 14 days after the last dose of study treatment.
17. Adequate baseline organ function, as demonstrated by the following:
• Serum creatinine less then or equal 2 x institutional ULN
• Serum albumin greater then or equal to 2.5 g/dl.
• Bilirubin less then or equal to 2.0 x institutional ULN.
• AST and ALT less then or equal to3.0 x institutional ULN.
18. Adequate baseline hematologic function, as demonstrated by the following:
• ANC greater then or equal to 1.5x109/L.
• Haemoglobin greater then or equal to 9 g/dL and no red blood cell (RBC) transfusions during the prior 14 days.
• Platelet count greater then or equal to 100x109/L and no platelet transfusions during the prior 14 days.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Participants with high-risk cutaneous SCC as per the National Comprehensive Cancer Network (NCCN) guidelines. High risk criteria includes depth of the tumour >2 mm, tumour diameter >2 cm, poor differentiation, perineural invasion, or involvement of the ear or lip mucosa. Additional high-risk factors include immunocompromised participants and
fast-growing or recurrent tumours.
2. Participants with morpheaform, metatypical, basosquamous, or infiltrating BCC histologies, if the target lesion is a recurrent BCC.
3. Participants with known metastatic disease from the disease to be studied, e.g., metastatic cutaneous SCC or BCC.
4. Any other known, active malignancy, except for treated cervical intraepithelial neoplasia, or non-melanoma skin cancer. Participants with a history of malignancies of low recurrence potential who have received curative-intent therapy may be approved on a case-by-case basis in discussion with study sponsor, if deemed unlikely to put participant at a higher risk of treatment-related toxicity and/or interfere with the integrity of study outcome.
5. Use of another investigational product within 60 days, within 5 half-lives, or twice the duration of biological effect, whichever is the longest, prior to INV043 PDT.
6. Current participation in any other investigational trial.
7. Participants have undergone skin punch biopsies on the target lesion within
14 days of INV043 PDT.
8. Participants with a history of sensitivity to any of the components in the IP
formulation.
9. Evidence of dermatological disease or histological evidence of a confounding
skin condition in the treatment area, including but not limited to superficial BCC, worse level/grade of BCC, rosacea, psoriasis, atopic dermatitis, eczema, or any other tumour in the treatment area.
10. Evidence of xeroderma pigmentosa or other genetic dermal conditions.
11. Participants with a diagnosis of porphyria.
Participants with a history of photodermatosis.
13. Use of drugs with phototoxic or photoallergic potential.
14. Treatment for any of the target lesions within 60 days of screening visit by
any of the following treatments: Liquid nitrogen, Photochemotherapy (psoralene and ultraviolet A radiation, PUVA), long wave ultraviolet radiation (UVB light), surgical excision or curettage within 2 cm of target lesion; Systemic retinoids; Ionizing radiation or intralesional injections or; Undergone a skin resurfacing procedure, i.e., chemical peel, laser resurfacing, dermabrasion within the last 30 days.
15. Treatment with the following topical agents within 30 days prior to the screening visit: methyl aminolevulinate, aminolevulinate, 5-fluorouracil, corticosteroids, retinoids, diclofenac, hyaluronic acid, imiquimod.
16. History of recurrence of the target lesion. Participants with recurrent target lesion may be allowed on a case-by-case basis in discussion with study Sponsor if deemed unlikely to put participant at a higher risk of treatment- related toxicity and/or interfere with the integrity of study outcome.
17. Systemic use of immunosuppressive drugs of > 10mg Prednisolone equivalent within 30 days prior INV043 PDT. Topical, inhaled, or limited duration steroid use, e.g., for contrast allergy prophylaxis, may be allowed on a case-by-case basis in discussion with study Sponsor if deemed unlikely to put participant at a higher risk of treatment-related toxicity and/or interfere with the integrity of study outcome.
18. Use of therapeutic anti-coagulant, including prophylactic anti-platelet therapy, that cannot be safely withheld for 14 days prior to and following INV043 PDT administration.
19. QTc interval > 450 ms (male) or > 470 ms (female).
20. Known or history of, or positive test result for, hepatitis B or C, human
immunodeficiency virus (HIV), syphilis or tuberculosis.
21. Uncontrolled clinically significant medical issues such as cardiac or
pulmonary disease, or an uncontrolled intercurrent illness including, but not limited to, uncontrolled infection requiring systemic therapy, uncontrolled diabetes mellitus, disseminated intravascular coagulation, psychiatric illness/social situations that would limit compliance with study requirements, or other conditions that may impair wound healing.
22. Any medical condition which, in the opinion of the Investigator, places the participant at an unacceptably high risk for toxicities or adverse clinical outcome.

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
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Sample size calculation for dose-escalation is based on the number of dose cohorts and number of subjects to be enrolled at each cohort according to 3+3 (Part 1) and accelerated titration design (Part 2).

This study will evaluate the safety, tolerability, preliminary efficacy and exploratory
pharmacodynamics of treatment with INV043 for dose escalation cohorts.


Participant inclusion into each population will be determined prior to the final analysis.

SAFETY ANALYSIS - The safety analysis set will include all participants who receive any amount of INV043 and will be used in the analysis of participant characteristics, disposition and safety data.

EFFICACY ANALYSIS - All participants who received treatment and have a post baseline response assessment per RECIST v1.1 or who discontinue prior to disease assessment due to clinical progression of disease will be included in the efficacy evaluable analysis set. All efficacy analyses will be based on the efficacy evaluable analysis set.

PHARMACODYNAMIC ANALYSIS - All participants who received treatment, and who a baseline and at least one post-baseline pharmacodynamic result will be included in the pharmacodynamic analysis set. All pharmacodynamic analyses will be based on the pharmacodynamic analysis set

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
30/04/2024
Actual
Date of last participant enrolment
Anticipated
30/07/2025
Actual
Date of last data collection
Anticipated
31/08/2026
Actual
Sample size
Target
150
Accrual to date
0
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 25979 0
Veracity Clinical Research - Woolloongabba
Recruitment postcode(s) [1] 41830 0
4102 - Woolloongabba

Funding & Sponsors
Funding source category [1] 315529 0
Commercial sector/Industry
Name [1] 315529 0
Invion Limited
Country [1] 315529 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Invion Limited
Address
100 Albert Road South Melbourne Victoria, Australia 3205
Country
Australia
Secondary sponsor category [1] 317614 0
None
Name [1] 317614 0
Address [1] 317614 0
Country [1] 317614 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 314429 0
Bellberry Human Research Ethics Committee
Ethics committee address [1] 314429 0
Ethics committee country [1] 314429 0
Australia
Date submitted for ethics approval [1] 314429 0
20/12/2023
Approval date [1] 314429 0
10/09/2024
Ethics approval number [1] 314429 0

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

Contacts
Principal investigator
Name 131550 0
Dr Lynda Spelman
Address 131550 0
Veracity Clinical Research, Suite 18, Level 1, 250 Ipswich Road Woolloongabba Qld 4102
Country 131550 0
Australia
Phone 131550 0
+61730391311
Fax 131550 0
Email 131550 0
spelchat@veracity.net.au
Contact person for public queries
Name 131551 0
Madeleine Supranowicz
Address 131551 0
Veracity Clinical Research, Suite 18, Level 1, 250 Ipswich Road Woolloongabba Qld 4102
Country 131551 0
Australia
Phone 131551 0
+61730391311
Fax 131551 0
Email 131551 0
madeleine@veracityclinical.net.au
Contact person for scientific queries
Name 131552 0
Lynda Spelman
Address 131552 0
Veracity Clinical Research, Suite 18, Level 1, 250 Ipswich Road Woolloongabba Qld 4102
Country 131552 0
Australia
Phone 131552 0
+61730391311
Fax 131552 0
Email 131552 0
spelchat@veracity.net.au

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.