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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04416516




Registration number
NCT04416516
Ethics application status
Date submitted
21/05/2020
Date registered
4/06/2020
Date last updated
25/08/2020

Titles & IDs
Public title
Safety and Efficacy of ASN-002 Combined With a Hedgehog Pathway Inhibitor
Scientific title
A Phase 2A Study to Assess the Safety and Efficacy of ASN-002 Combined With a Hedgehog Pathway Inhibitor in the Treatment of Multiple Low Risk Basal Cell Carcinomas in Sporadic or Basal Cell Nevus Syndrome Patients
Secondary ID [1] 0 0
ASN-002-003
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Basal Cell Carcinoma 0 0
Basal Cell Nevus Syndrome 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - ASN-002

Experimental: Arm 1, Patients with 1 Tumour - Participants with 1 Target Tumour will receive 3 x ASN-002 1.0x10(11) Injections
+ VISMODEGIB (150 mg) daily for 4 weeks.

Experimental: Arm 2, Patients with 3 or more Tumours - Participants with 3 or more Target Tumours will receive 3 x ASN-002 1.0x10(11) Injections (per tumour) + VISMODEGIB (150 mg) daily for 4 weeks.


Other interventions: ASN-002
ASN-002 has been designed for clinical applications, especially for intratumoral administration in the treatment of various cancers. This rAd vector delivers the gene of interest, in the case of ASN-002 the human IFN? gene, into target cells. The rAd vector in ASN-002 is replication deficient and although it infects cells, it is not able to replicate in the tumor or in normal human cells. The infected cells are able to transcribe and translate the IFN? DNA leading to a sustained local concentration of IFN? in the tumor mass that is designed to avoid high levels of systemic IFN? that may be lead to unacceptable toxicity.

Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of ASN-002 related Adverse Events in patients with previously untreated nBCC - Incidence of Adverse Adverse events will be monitored
Timepoint [1] 0 0
Participants will be followed up to 6 months
Primary outcome [2] 0 0
Microscopic clearance of the injected Target basal cell carcinoma. - Histological clearance (HC) will be defined as the absence of detectable evidence of BCC tumor cell nests in serial histological samples as determined by central pathology review.
Timepoint [2] 0 0
Microscopic examinations of sample collected at weeks 25-33 after the first dose.
Secondary outcome [1] 0 0
Microscopic clearance of the injected Non-Target basal cell carcinoma. - Histological clearance (HC) will be defined as the absence of detectable evidence of BCC tumor cell nests in serial histological samples as determined by central pathology review.
Timepoint [1] 0 0
Microscopic examinations of sample collected at weeks 25-33 after the first dose.

Eligibility
Key inclusion criteria
1. Histologically confirmed previously untreated, BCC (nodular and superficial), 5-20 mm
in maximum diameter, per the selection criteria for study BCC tumours. A punch biopsy
(refer to study procedure manual for biopsy size selection) from the thickest part of
all the target tumours is required for histological confirmation of BCC and to exclude
BCC non-eligible subtypes.

Note: If a patient has mix of nodular and superficial BCC tumours, at least one target
tumour should be a nodular BCC.

2. Removal of < 25% of the area of each biopsied tumour by initial biopsy performed 1-12
weeks before Day 1. If the initial biopsy was performed >8 weeks prior to screening,
the investigator may re-biopsy the tumour, provided not > 25% of the area of the
original tumour is removed. Non-study tumours may be resected or treated at the
discretion of the Investigator prior to study entry or if they develop during the
study.

3. Hedgehog pathway inhibitor treatment naïve.

4. Acceptable general health as determined by the investigator, i.e. no serious or active
medical or psychiatric illness or recreational or therapeutic drug or alcohol use
that, in the opinion of the Investigator, would interfere with treatment, assessment
or compliance with the protocol, ability to provide informed consent, or patient
safety.

5. 18 years of age or older.

6. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2.

7. Screening laboratory values as follows:

1. Neutrophil count > 1500/mm3

2. Haemoglobin > 9 g/dL

3. Platelet count >100,000/mm3

4. Prothrombin INR < 1.5

5. Total bilirubin < 1.5 X upper limit of normal (ULN), except in the case of known
Gilbert's syndrome

6. Aspartate transaminase (AST), alanine transaminase (ALT) or alkaline phosphatase
(ALP) < 2X ULN

7. Creatinine < 1.5 X upper limit of normal (ULN)

8. Female patients who are documented infertile, postmenopausal for at least 1 year,
surgically sterile or using acceptable and highly effective birth control for the
duration of the study and for at least 3 months after last administration of the study
treatments.

9. Male patients with female partners of child bearing potential, agreement to use two
adequate contraception methods while being on vismodegib and for 3 months of
completion. agreement not to donate semen for 3 months after completion of vismodegib.

10. Written informed consent prior to initiation of study-specified procedures.

11. Able and willing to comply with all study requirements, including surgical removal of
tumour/tumour site at completion of study.

12. Baseline tissue sample adequate for determination of histological or other biomarkers.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria

1. Known or suspected metastatic disease or other active, invasive malignancy.

2. Female patients of childbearing potential who are lactating or pregnant (negative
serum pregnancy test needed prior to dosing).

3. Clinically active or uncontrolled skin disease or tattoos that would interfere with
evaluation of the area surrounding the target tumour (e.g. eczema, unstable psoriasis,
xeroderma pigmentosa).

4. Known history of sensitivity to any of the ingredients in ASN-002 and any Hh pathway
inhibitors.

5. Immunocompromised (e.g. known Hepatitis B or 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).

6. Has received or is expected to receive treatment with psoralen plus UVA or UVB therapy
within 6 months of the Screening visit.

7. Any prior systemic anti-tumour therapy or local treatment for target tumours prior to
first dose.

8. History of immunological disorder, severe allergic reaction, moderate or severe asthma
or known history of anaphylaxis or any other serious adverse reactions to any
medication.

9. Any experimental or investigational agents within one month of first ASN-002
injection.

10. Any prior exposure to TG1041, TG1042 (ASN-002), any other adenoviral-based
experimental agent, or any form of gene therapy within 6 months of first dose of
vismodegib in the study.

11. Any prior exposure to vismodegib or any other Hh inhibitor within 6 months of first
dose in the study.

12. Current therapy with any medications recognized to cause rhabdomyolysis or a prior
history of rhabdomyolysis.

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 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 0 0
Central Brisbane Dermatology - Brisbane
Recruitment postcode(s) [1] 0 0
4000 - Brisbane

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Ascend Biopharmaceuticals Ltd
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The primary objectives are to:

1. Evaluate the safety and tolerability of intralesional ASN-002 when administered in
combination with oral vismodegib in patients with Basal Cell Carcinomas (BCC)s;

2. Evaluate the efficacy of intralesional ASN-002 in target tumours when administered in
combination with oral vismodegib in patients with BCCs.

The secondary objective is to:

1) Evaluate the efficacy of intralesional ASN-002 in non-target tumours when administered in
combination with oral vismodegib in patients with BCCs.

The exploratory objective is to:

1) Evaluate immunological biomarkers during the course of treatment.
Trial website
https://clinicaltrials.gov/show/NCT04416516
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clement Leong, Ph.D
Address 0 0
Ascend Biopharmaceuticals Ltd
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Clement Leong, Ph.D
Address 0 0
Country 0 0
Phone 0 0
+61 421 837 218
Fax 0 0
Email 0 0
clementleong@ascendbiopharma.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04416516