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Trial registered on ANZCTR


Registration number
ACTRN12618000140257
Ethics application status
Approved
Date submitted
23/01/2018
Date registered
30/01/2018
Date last updated
24/01/2020
Date data sharing statement initially provided
24/01/2020
Date results provided
24/01/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase I, single centre, open label, escalating dose study to assess the safety, tolerability and immunogenicity of a therapeutic Human Papilloma Virus (HPV) DNA vaccine (AMV002) for HPV-associated head and neck cancer (HNC) after curative treatment.
Scientific title
A Phase I, single centre, open label, escalating dose study to assess the safety, tolerability and immunogenicity of a therapeutic Human Papilloma Virus (HPV) DNA vaccine (AMV002) for HPV-associated head and neck cancer (HNC) after curative treatment.
Secondary ID [1] 293840 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
HPV associated oropharyngeal squamous cell carcinoma 306288 0
Condition category
Condition code
Cancer 305375 305375 0 0
Head and neck

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is an open label first-in-human study evaluating three escalating doses of HPV DNA vaccine (AMV002), each given by a nurse three times by ID injection to the forearm, administered four weeks apart to HPV-associated oropharyngeal squamous cell carcinoma patients in remission following curative treatment. The minimum dose is 0.25mg and maximum dose is 4mg.
Intervention code [1] 300100 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 304521 0
Safety and tolerability. Possible adverse events include erythema, induration and pain at the injection site. After vaccination the participant will be given a diary to record these and any other adverse events for 1 week.
Timepoint [1] 304521 0
The incidence and severity of adverse events in each treatment group, including vaccine related adverse events will be measured from enrollment until the end of study visit. There are 8 visits including screening and at days 0, 7, 28, 35, 56, 63 and 84.
Secondary outcome [1] 342221 0
The immunogenicity of AMV002 will be assessed by measuring anti-HPV antibodies in the participant's serum and measuring the cell mediated response in the peripheral blood mononuclear cells by interferon gamma enzyme linked immunospot assay.
Timepoint [1] 342221 0
At day 0 pre-treatment and days 7, 28, 35, 56, 63 and 84 post treatment.

Eligibility
Key inclusion criteria
1. Diagnosed with a loco-regional confined HPV-associated OPSCC
2. Have results from local testing of HPV positivity for oropharyngeal cancer defined as a positive test for HPV16 DNA or HPV16 mRNA or p16 immunohistochemistry (IHC) testing using CINtec® p16 Histology assay and a 70% cut-off point. If HPV status has previously been tested using one of these procedures, no retesting is required, however HPV16 DNA or HPV16 mRNA testing may be performed on archived paraffin-embedded tumour tissue if not previously done.
3. Received curative intent treatment which may include any of the following: surgery, chemotherapy and/or radiotherapy (RT).
4. Completed curative treatment at least 12 weeks prior and undergone re-staging scans confirming loco-regional complete response and no evidence of distant disease.
5. World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at enrolment
6. Able to communicate effectively with study personnel and is considered reliable, willing, and cooperative in terms of compliance with the protocol requirements.
7. Written informed consent signed prior to entry into the study.
8. Aged greater than or equal to 18 years at the time of informed consent.
9. Males who are not surgically sterile must use a condom through to study completion and for 1 month after the last vaccination, unless they have a female partner who is surgically sterile or post-menopausal. They must refrain from fathering a child during this time.
10. Women of child-bearing potential (WOCBP) must use highly effective contraceptive measures (failure rate of < 1% per year when used consistently and correctly) and intend to continue use of contraception for at least 3 months following the last vaccination. Highly effective contraceptive measures could include: combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation, progestogen-only hormonal contraception associated with inhibition of ovulation, intrauterine device, intrauterine hormone releasing system, bilateral tubal occlusion, vasectomized partner, and sexual abstinence.
11. Participant in otherwise general good health based on medical history and physical examination.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Histologically or cytologically confirmed head and neck cancer of any other primary anatomic location in the head and neck, including participants with Head and Neck Squamous Cell Carcinoma (HNSCC) of unknown primary or non-squamous histologies (e.g., nasopharynx or salivary gland), not specified in the inclusion criteria.
2. Birthmarks, tattoos, wound or other skin conditions on the forearms that could reasonably obscure injection site reactions.
3. Inadequate venous access to allow collection of blood samples.
4. Breastfeeding or pregnant as confirmed by a positive serum beta human chorionic gonadotropin (ß-HCG) pregnancy test at Screening or subsequent clinic visits.
5. Current acute or chronic disease, other than the study indication, that would increase the expected risk of exposure to the investigational product or would be expected to interfere with the planned evaluations, in the judgment of the Investigator.
6. Received medication known to have anti-HPV activity within 28-days of screening
(Note: prior vaccination with HPV prophylactic vaccines is not an exclusion criterion for this study).
7. Laboratory blood values:
a) Haemoglobin <10.0 grams/decilitre (g/dL)
b) Neutrophil count <1000/mm3
c) Platelet count <80000/mm3
d) Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >1.5 times the upper limit of normal (ULN)
e) Amylase >1.5 times ULN (unless serum lipase is less than or equal to 1.5 times ULN)
f) Subjects with an estimated creatinine clearance of <60 mL/minute (min)
g) International Normalised Ratio (INR) > ULN
h) Hepatitis B surface antigen (HBsAg), Hepatitis C Virus (HCV) antibody or Human Immunodeficiency Virus (HIV) antibody positive.
8. Received any prophylactic or therapeutic vaccine, or investigational drug, within 4 weeks of first vaccination.
9. History of severe allergy (requiring hospital care), severe reaction to any drug or prior vaccination, or any known or suspected allergies or sensitivities to the study drug or its constituents.
10. Unwilling to abstain from blood donation during the course of the study, and/or has donated blood or plasma within 60 days prior to the Screening visit.

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
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Since the study is a pilot without consideration given to formal hypothesis testing and statistical power, the focus of the statistical analysis will be descriptive. As such, summary descriptive statistics relevant for the various endpoints will be provided and no statistical testing is planned.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
31/01/2018
Actual
15/05/2018
Date of last participant enrolment
Anticipated
29/08/2018
Actual
16/04/2019
Date of last data collection
Anticipated
26/11/2018
Actual
11/07/2019
Sample size
Target
12
Accrual to date
Final
12
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 9862 0
Princess Alexandra Hospital - Woolloongabba
Recruitment postcode(s) [1] 18647 0
4102 - Woolloongabba

Funding & Sponsors
Funding source category [1] 298459 0
Commercial sector/Industry
Name [1] 298459 0
Admedus Vaccines Pty Ltd
Country [1] 298459 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Admedus Vaccines Pty Ltd
Address
PO Box 836
Stones Corner QLD 4120
Country
Australia
Secondary sponsor category [1] 297600 0
None
Name [1] 297600 0
Address [1] 297600 0
Country [1] 297600 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299450 0
Metro South Hospital and Health Service Human Research Ethics Committee
Ethics committee address [1] 299450 0
Ethics committee country [1] 299450 0
Australia
Date submitted for ethics approval [1] 299450 0
19/10/2017
Approval date [1] 299450 0
21/11/2017
Ethics approval number [1] 299450 0
HREC/17/QPAH/726

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

Contacts
Principal investigator
Name 80442 0
Prof Sandro Porceddu
Address 80442 0
Princess Alexandra Hospital
199 Ipswich Rd
Woolloongabba QLD 4102
Country 80442 0
Australia
Phone 80442 0
+61 7 3176 7853
Fax 80442 0
Email 80442 0
Sandro.Porceddu@health.qld.gov.au
Contact person for public queries
Name 80443 0
Neil Finlayson
Address 80443 0
Admedus Vaccines Pty Ltd
PO Box 836
Stones Corner QLD 4120
Country 80443 0
Australia
Phone 80443 0
+61 7 3443 6996
Fax 80443 0
Email 80443 0
nfinlayson@admedusimmunotherapies.com
Contact person for scientific queries
Name 80444 0
Neil Finlayson
Address 80444 0
Admedus Vaccines Pty Ltd
PO Box 836
Stones Corner QLD 4120
Country 80444 0
Australia
Phone 80444 0
+61 7 3443 6996
Fax 80444 0
Email 80444 0
nfinlayson@admedusimmunotherapies.com

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
EmbaseA phase 1, single centre, open label, escalating dose study to assess the safety, tolerability and immunogenicity of a therapeutic human papillomavirus (HPV) DNA vaccine (AMV002) for HPV-associated head and neck cancer (HNC).2021https://dx.doi.org/10.1007/s00262-020-02720-7
EmbaseCurrent status and perspective of tumor immunotherapy for head and neck squamous cell carcinoma.2022https://dx.doi.org/10.3389/fcell.2022.941750
EmbaseNovel Immunotherapeutic Approaches to Treating HPV-Related Head and Neck Cancer.2023https://dx.doi.org/10.3390/cancers15071959
EmbaseSkin-Grafting and Dendritic Cell "Boosted" Humanized Mouse Models Allow the Pre-Clinical Evaluation of Therapeutic Cancer Vaccines.2023https://dx.doi.org/10.3390/cells12162094
EmbaseThe Role of Different Immunocompetent Cell Populations in the Pathogenesis of Head and Neck Cancer-Regulatory Mechanisms of Pro- and Anti-Cancer Activity and Their Impact on Immunotherapy.2023https://dx.doi.org/10.3390/cancers15061642
N.B. These documents automatically identified may not have been verified by the study sponsor.