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Trial registered on ANZCTR


Registration number
ACTRN12624001138572
Ethics application status
Approved
Date submitted
26/07/2024
Date registered
20/09/2024
Date last updated
20/09/2024
Date data sharing statement initially provided
20/09/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase 1/2a, First-In-Human, Single and Multiple Ascending Dose Escalation and Dose Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Clinical Efficacy of Intralesional FLD-103 in Subjects with Basal Cell Carcinoma (BCC)
Scientific title
A Phase 1/2a, First-In-Human, Single and Multiple Ascending Dose Escalation and Dose Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Clinical Efficacy of Intralesional FLD-103 in Subjects with Basal Cell Carcinoma (BCC)
Secondary ID [1] 312079 0
P01-CLIN01
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Basal Cell Carcinoma 333704 0
Condition category
Condition code
Cancer 330385 330385 0 0
Non melanoma skin cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a multi-centre, phase 1, open-label, single ascending dose (SAD) and multiple ascending dose (MAD) study, to determine the safety, tolerability and pharmacokinetics of intralesional FLD-103 when administered to subjects with Basal Cell Carcinoma (BCC). FLD-103 will be injected directly in the central areas of the tumour.

This Phase of the study is planned to enrol approximately 18 subjects with BCC. Each subject will receive either a single dose of FLD-103 or doses of FLD-103 once weekly for four (4) weeks. FLD-103 is comprised of two (2) components, FSD147L and PMO-Gli1 formulated as an intralesional injection.

FLD-103 is provided as a ready-to-use formulation in single-use sterile 1.0 mL vials filled with 0.80 mL of IP solution. The volume of FLD-103 to be injected throughout the study will be determined by the initial size of the lesion, at Baseline.

In Part 1, participants will be assigned to receive one of three dose levels. Either 0.5 mg/ml (cohort 1SAD and 1MAD), 1.0 mg/mL (cohort 2SAD and 2MAD) or 3.0 mg/mL (cohort 3SAD and 3MAD) of FLD-103 in an open-label fashion.

Up to six (6) single and multiple dose Cohorts of 3 + 3 eligible subjects will be studied in Part 1 (Phase 1) initially, as required.
Participants will be assigned to either the SAD or MAD based on the timing of their screening visit.

Three subjects are planned initially to enrol into each of six (6) sequential Cohorts according to a detailed Dose Level Guide:
- Three (3) Cohorts – Cohorts 1s, 2s, and 3s will be administered a single dose of FLD-103, and
- Three (3) Cohorts – Cohorts 1m, 2m, and 3m will be administered FLD-103 once weekly for four (4) weeks.
A sentinel subject will be required in each Single Ascending Dose Cohort.
A review of the sentinel subject will be made by the Principal Investigator and Medical Monitor 48 hours after their dosing. If no safety concerns are reported, the remaining two (2) subjects in the Cohort will be dosed a minimum of 24 hours after the completion of the safety evaluation of the sentinel subject in that Cohort.

Once all subjects of a Cohort have been dosed, all available safety and tolerability data, from evaluable subjects to Day 8 for the single dose Cohorts or Day 29 for the multiple dose Cohorts, will be reviewed by the Safety Review Committee (SRC). According to the occurrence of Dose Limiting Toxicity (DLT) within the initial three (3) subjects within a Cohort, the SRC will make a recommendation: 1) escalate to the next dose level (DL) (and initiate concurrent multiple dosing at the current DL, if applicable), 2) enrol three (3) additional subjects at the current dose or 3) the current dose is not tolerated, meaning that the MTD has been exceeded. SRC will then have the option to declare the previous dose as the MTD or recommend enroling three (3) additional subjects to the previous DL Cohort.

It is anticipated that a total of three (3) dose concentrations of FLD-103 (DL1: 0.50 mg/mL FSD147L / 0.63 mg/mL PMO-Gli1; DL2: 1.00 mg/mL FSD147L / 1.26 mg/mL PMO-Gli1 and DL3: 3.00 mg/mL FSD147L / 3.77 mg/mL PMO-Gli1) will be administered in the study. However, based on the SRC review of each individual Cohort, the total number of Cohorts and the doses administered may be revised.
Intervention code [1] 328528 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 338157 0
SAD Study - To evaluate the safety and tolerability of ascending single intralesional doses of FLD-103 administered to subjects with BCC
Timepoint [1] 338157 0
Adverse events - The Investigator will make an assessment of severity for each AE and SAE reported during the study. AEs will be scored in accordance with the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. The severity of each AE and SAE will be assessed continuously as they are reported or observed and reviewed daily up until end of study (EOS) visit at Day 46.

Local Skin Response (LSR) and other potential localised responses will be performed at screening, pre-dose on Day 1, and post-dose on Day 1, Day 2, Day 3, Day 8, Day 15, Day 29 and Day 36.

Vital signs - Measured at screening, pre-dose on Day 1, and post-dose on Day 1, Day 2, Day 3, Day 8, Day 15, Day 29 and Day 36. Vital signs consist of blood pressure and heart rate which will be measured using a sphygmomanometer, respiratory rate by manual breath count and temperature by thermometer.

Electrocardiogram (ECG) - 12-lead ECG recordings will be obtained in triplicate at screening, pre-dose on Day 1, and post-dose on Day 1, Day 2, Day 3, and Day 36.

Clinical laboratory evaluations (clinical chemistry, hematology, coagulation, routine urinalysis - blood and urine samples will be collected at screening and pre-dose at Day 1, Day 2, Day 3, Day 8, and Day 36.

Development of anti-FLD-103 antibodies - A blood sample will be collected pre-dose on Day 1, Day 8 and Day 29.
Primary outcome [2] 338203 0
MAD Study - To evaluate the safety and tolerability of ascending multiple intralesional doses of FLD-103 administered to subjects with BCC
Timepoint [2] 338203 0
Adverse events - The Investigator will make an assessment of severity for each AE and SAE reported during the study. AEs will be scored in accordance with the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. The severity of each AE and SAE will be assessed continuously as they are reported or observed and reviewed daily up until end of study (EOS) visit at Day 67.

Local Skin Response (LSR) and other potential localised responses - Assessed at screening, pre-dose on Day 1, Day 2, Day 3 (if needed), Day 8, Day 9, Day 15, Day 15, Day 22 and post-dose at Day 23, Day 29, Day 36, Day 43, Day 50 and Day 57.

Vital signs - Measured at screening, pre-dose on Day 1, Day 8, Day 16 and Day 22 and post-dose on Day 1, Day 2, Day 3 (if needed), Day 9, Day 16, Day 23, Day 29, Day 36 , Day 43, Day 50 and Day 57. Vital signs consist of blood pressure and heart rate which will be measured using a sphygmomanometer, respiratory rate by manual breath count and temperature by thermometer.

Electrocardiogram (ECG) - 12-lead ECG recordings will be obtained in triplicate at screening, pre-dose at Day 1, Day 8, Day 15 and Day 22 and post-dose at Day 2 and Day 57.

Clinical laboratory evaluations (clinical chemistry, hematology, coagulation, routine urinalysis - Blood and urine samples will be collected at screening and pre-dose at Day 1, Day 8, Day 15 and Day 22 and post-dose at Day 2, Day 29 and Day 57.

Development of anti-FLD-103 antibodies - A blood sample will be collected pre-dose on Day 1 and Day 8 and post-dose on Day 29.
Secondary outcome [1] 434750 0
SAD Study - To evaluate the pharmacokinetics (PK) of FLD-103 following single
intralesional doses administered to subjects with BCC
Timepoint [1] 434750 0
Blood plasma samples will be collected via venepuncture pre-dose on Day 1 and post-dose on Day 1, Day 2, Day 3 and Day 8.
Secondary outcome [2] 434956 0
MAD Study - To evaluate the pharmacokinetics (PK) of FLD-103 following multiple intralesional doses administered to subjects with nBCC
Timepoint [2] 434956 0
Blood plasma samples will be collected via venepuncture pre-dose on Day 1, Day 8, Day 15 and Day 22 and post-dose on Day 29 and Day 36
Secondary outcome [3] 434957 0
SAD Study - To make a preliminary assessment of tumour response to FLD-103
Timepoint [3] 434957 0
Lesion assessment and measurement will be performed at Screening, pre-dose on day 1, then post-dose on day 8, day 15, day 29 and day 36.
Secondary outcome [4] 438955 0
MAD Study - To make a preliminary assessment of tumour response to FLD-103
Timepoint [4] 438955 0
Lesion assessment and measurement will be performed at Screening, pre-dose on day 1, day 8, day 15, day 22, then post dose on day 29, day 36, day 43. day 50 and day 57.
Secondary outcome [5] 439620 0
SAD Study - To make a preliminary assessment of tumour response to FLD-103
Timepoint [5] 439620 0
Lesion assessment and measurement will be performed at Screening, pre-dose on day 1, then post-dose on day 8, day 15, day 29 and day 36.
Secondary outcome [6] 439621 0
MAD Study - To make a preliminary assessment of tumour response to FLD-103
Timepoint [6] 439621 0
Lesion assessment and measurement will be performed at Screening, pre-dose on day 1, day 8, day 15, day 22, then post dose on day 29, day 36, day 43. day 50 and day 57.
Secondary outcome [7] 439622 0
SAD Study - To make a preliminary assessment of tumour response to FLD-103
Timepoint [7] 439622 0
Lesion assessment and measurement will be performed at Screening, pre-dose on day 1, then post-dose on day 8, day 15, day 29 and day 36.
Secondary outcome [8] 439623 0
MAD study - To make a preliminary assessment of tumour response to FLD-103
Timepoint [8] 439623 0
Lesion assessment and measurement will be performed at Screening, pre-dose on day 1, day 8, day 15, day 22, then post dose on day 29, day 36, day 43. day 50 and day 57.

Eligibility
Key inclusion criteria
1. At least 18 years of age and up to 85 years of age, inclusive, at the time of signing the informed consent.
2. 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.
3. At Screening, the subject must have at least a single histologically confirmed nBCC suitable for treatment and final excision by the Investigator.
4. A nBCC previously biopsied outside the study as part of standard clinical practice may be re-biopsied within the study, provided that less than 25 percent of the area of the nodular lesion is removed as a result of the second biopsy.
5. Target nBCC must be appropriate for a full thickness 2 mm punch biopsy (for lesions from 5 mm up to less than 10 mm diameter) or 3 mm punch biopsy (for lesions from 10 mm to less than 20 mm diameter), taken approximately halfway from the centre or outer border of each target nBCC, within 28 to 42 days prior to Day 1 for histological confirmation at Screening. The biopsy(ies) must remove less than 25 percent of the area of the nBCC.
6. Target BCC must, in the assessment of the Investigator, be appropriate for FLD-103 intralesional treatment over the anticipated duration of the study.
7. Female volunteers, must:
a. Be of non-child-bearing potential i.e., surgically sterilised (hysterectomy, bilateral salpingectomy, bilateral oophorectomy) at least 6 weeks before the Screening visit, or
b. Be postmenopausal (where postmenopausal is defined as no menses for 12 months without an alternative medical cause and follicle-stimulating hormone (FSH) level and estradiol level consistent with postmenopausal status, per local laboratory guidelines).
8. Male volunteers, must:
a. Agree not to donate sperm from signing the consent form until at least 90 days after the last dose of study drug.
b. If engaging in sexual intercourse with a female partner who could become pregnant, agree to use adequate contraception (defined as use of a condom combined with use of a highly effective method of contraception from signing the consent form until at least 90 days after the last dose of study drug.
c. If engaging in sexual intercourse with a female partner who is not of childbearing potential or a same-sex partner, agree to use a condom from signing the consent form until at least 90 days after the last dose of study drug.
Minimum age
18 Years
Maximum age
85 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Women of childbearing potential.
2. History of sensitivity to any of the components in the Investigational Product (IP) formulation.
3. Target lesion in high-risk anatomic location (e.g. ocular/peri-ocular, nose/perinasal, ears, lips/perioral, scalp, fingers/hands).
4. Target lesion requiring immediate surgical removal.
5. Histologically confirmed concurrent diagnosis of locally advanced or metastatic BCC.
6. Use of known inhibitors of the HH signaling pathway (including but not limited to vismodegib, sonidegib, itraconazole) within six (6) months of Screening.
7. Use of topical or intralesional treatment within 5 cm of the target BCC (e.g. 5-FU, topical corticosteroids, retinoids) within the specified period
8. Use of topical imiquimod, anywhere on the body, within six (6) months of Screening.
9. Use of any other systemic therapy, within the specified period.
10. Any prior exposure to TG1041, TG1042 (ASN-002), any other adenoviral-based experimental agent, or any form of gene therapy within six (6) months of Screening.
11. Has received or is expected to receive phototherapy, including treatment with psoralen plus UVA or UVB therapy, within six (6) months of the Screening visit or during the study.
12. Use of another Investigational Product (IP) within three (3) months or five (5) halflives or twice the duration of biological effect (whichever is the longest) preceding the first dose of FLD-103.
13. Previous superficial radiation therapy for acne or other cutaneous disorder.
14. A history of, or current hepatic disease, or known hepatic or biliary abnormalities that in the opinion of the Investigator would preclude the subject from participation in the study.
15. Moderate to severe renal impairment, including subjects on chronic renal dialysis and subjects with a history of nephrectomy or kidney transplant (regardless of renal function)
16. History of anaphylaxis, anaphylactoid (resembling anaphylaxis) reactions, or severe allergic responses.
17. Alcohol or drug abuse within the past 180 days, a positive pre-study drug screen or other current mental health condition (including, but not
limited to, psychiatric disorder or dementia), which may affect study compliance or prevent understanding of the aims, investigational procedures, or possible consequences of the study.
18. History or current evidence of any condition, laboratory abnormality or situation which, in the Investigator’s opinion, may put the subject’s safety at significant risk, confound the study results, interfere with the evaluation of the target lesion/treatment area or interfere with the subject’s participation in the study, (for example, but not limited to, other clinically active or uncontrolled skin disorders or tattoos that would interfere with evaluation of the area surrounding the target BCC, uncontrolled systemic disease such as metabolic dysfunction, organ transplant patients, immunocompromised patients, and any other physical examination findings, or abnormal clinical laboratory findings).
19. Diagnosis of Xeroderma Pigmentosum or any other skin disorder that is associated with an abnormal rate of development of skin cancers or which may interfere with administration of the treatment and/or assessment of the target nBCC.
20. History of any malignancy within the past five (5) years or has a known malignancy that is progressing or requires active treatment excluding BCC or squamous cell carcinoma in situ or in situ cervical cancer or other low risk cancer like prostate cancer, Gleason score 6 or lower.
21. Treatment with any anti-platelet and/or anticoagulant medication.
22. Immunocompromised (e.g. Hepatitis A or B infection, current Hepatitis C infection, HIV infection) or receiving or expected to receive an immunomodulating agent (including immunosuppressive agents, cytotoxic drugs, biological agents, immunoglobulins, interferon or other immune or cytokine-based therapies. Use of inhaled or oral corticosteroids at doses higher than physiological replacement doses is an exclusion criterion).
23. Pulse rate less than 40 or greater than 100 bpm; systolic blood pressure (SBP) greater than 140 mmHg; diastolic blood pressure (DBP) greater than 90 mmHg at Screening after resting for five (5) minutes in a supine or semi-recumbent position. Repeat measurements are allowed at the discretion of the Investigator.
24. Any clinically significant abnormalities at Screening in rhythm, conduction or morphology of the 12-lead ECG, as considered by the Investigator, that may interfere with the interpretation of QTc interval changes including abnormal ST-T wave morphology.
25. Prolonged QTcF (QT interval corrected for heart rate using Fridericia’s formula) greater than 450 ms for male subjects or greater than 470 ms for female subjects, or a shortened QTcF less than 300 ms or a family history of prolonged QT syndrome, at Screening.
26. Plasma donation within the 14 days prior to Screening or any whole blood donation/significant blood loss greater than 500 mL during the three (3) months prior to Screening.
27. Subject with poor glycemic control who, within the last four months, initiated insulin treatment (e.g., oral agents, insulin pump or daily injections) or plan to do so in the next four (4) months.

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

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
21/10/2024
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
18
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,VIC

Funding & Sponsors
Funding source category [1] 316438 0
Commercial sector/Industry
Name [1] 316438 0
Feldan Therapeutics
Country [1] 316438 0
Canada
Primary sponsor type
Commercial sector/Industry
Name
Feldan Therapeutics
Address
Country
Canada
Secondary sponsor category [1] 318607 0
Commercial sector/Industry
Name [1] 318607 0
Avance Clinical
Address [1] 318607 0
Country [1] 318607 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 315230 0
Bellberry Human Research Ethics Committee
Ethics committee address [1] 315230 0
https://www.bellberry.com.au
Ethics committee country [1] 315230 0
Australia
Date submitted for ethics approval [1] 315230 0
19/06/2024
Approval date [1] 315230 0
07/08/2024
Ethics approval number [1] 315230 0

Summary
Brief summary
This study aims to determine the safety, tolerability and pharmacokinetics of intralesional FLD-103 when administered to subjects with Basal Cell Carcinoma.

Who is it for?
You may be eligible to join this study if you are a male or female aged 18 to 85 years old and have at least a single histologically confirmed nBCC suitable for treatment. A nBCC previously biopsied outside the study as part of standard clinical practice may be re-biopsied within the study, provided that less than 25 percent of the area of the nodular lesion is removed as a result of the second biopsy.

Study details
All participants who meet the eligibility criteria in this study will receive either a single dose of FLD-103 or doses of FLD-103 once weekly for four (4) weeks. FLD-103 is comprised of two (2) components, FSD147L and PMO-Gli1 formulated as an intralesional injection.
During and after completion of the treatment participants will be assessed for safety and tolerability of FLD-103, plasma PK and tumor response.
It is hoped the research in the Dose Escalation Phase (Part 1) will determine the maximum dose of FLD-103 that can be administered safely without causing severe reactions. Once Part 1 is completed, Part 2 will then evaluate one or more dose level(s) deemed to be safe and well tolerated, based on the data from the Part 1 of the study.

A sentinel subject will be required in each Single Ascending Dose Cohort. .

Once all subjects of a Cohort have been dosed, all available safety and tolerability data, from evaluable subjects will be reviewed.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 134062 0
Dr Juliana Junger
Address 134062 0
NovaTrials, Level 1, 10 Bradford Close, Kotara, NSW 2289
Country 134062 0
Australia
Phone 134062 0
+61 2 4089 3744
Fax 134062 0
Email 134062 0
[email protected]
Contact person for public queries
Name 134063 0
Catherine Lippe
Address 134063 0
Feldan Therapeutics, 2666 Boul. du Parc-Technologique, Suite 290, Quebec QC G1P 4S6 Canada
Country 134063 0
Canada
Phone 134063 0
+1 418 872 7277
Fax 134063 0
Email 134063 0
[email protected]
Contact person for scientific queries
Name 134064 0
Catherine Lippe
Address 134064 0
Feldan Therapeutics, 2666 Boul. du Parc-Technologique, Suite 290, Quebec QC G1P 4S6 Canada
Country 134064 0
Canada
Phone 134064 0
+1 418 872 7277
Fax 134064 0
Email 134064 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

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No documents have been uploaded by study researchers.

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No additional documents have been identified.