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Trial registered on ANZCTR


Registration number
ACTRN12622001203741
Ethics application status
Approved
Date submitted
2/09/2022
Date registered
8/09/2022
Date last updated
13/09/2023
Date data sharing statement initially provided
8/09/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Phase I clinical study to evaluate the safety and tolerability of Quadrivalent Influenza Vaccine (QIV) delivered intradermally by a high-density micro-array patch (HD MAP), compared to intramuscular Influvac® Tetra injection, in healthy adults aged 18 to 50 years
Scientific title
Phase I clinical study to evaluate the safety and tolerability of Quadrivalent Influenza Vaccine (QIV) delivered intradermally by a high-density micro-array patch (HD MAP), compared to intramuscular Influvac® Tetra injection, in healthy adults aged 18 to 50 years
Secondary ID [1] 307899 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
respiratory infection 327534 0
Influenza 327577 0
Condition category
Condition code
Respiratory 324636 324636 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
• QIV HD-MAP intradermal (ID) delivery system (VXS-1222) (active);
• Uncoated, vaccine-free HD-MAP ID delivery system (VXS 1222U) (inactive);
• Influvac® Tetra (Northern Hemisphere [NH] 2022/2023) intramuscular (IM) injection (active comparator).
VXS-1222 is an integrated, single-use, ID QIV delivery system containing a mechanical, dome-spring that applies an array of micro-projections to the skin at approximately 20 m/s. The spring is actuated by pressing down on the top of the applicator with a finger and the whole delivery system (including the HD-MAP) is removed after two minutes of application time.
VXS-1222 (active) includes an aseptically produced 0.64 cm² polymer array (or ‘patch’) with approximately 1,600 micro-projections. VXS-1222 (active) HD-MAP will be coated with 30 µg, 60 µg or 100 µg HA of QIV. Based on an estimated 70% transfer of QIV into study participants, approximately 21, 42 or 70 µg of QIV will be delivered ID per VXS 1222 HD-MAP application.
The QIV to be used in VXS-1222 (active) is comprised of the following 2022/2023 Northern Hemisphere strains:
• A/Victoria/2570/2019 (H1N1) pdm09-like strain;
• A/Darwin/9/2021 (H3N2)-like strain;
• B/Austria/1359417/2021-like strain (Victoria lineage);
• B/Phuket/3073/2013-like strain (Yamagata lineage).
The QIV virus strain composition is identical to Influvac Tetra (NH 2022/2023) (active comparator). These are also the same strains that were used in the TGA-approved Southern Hemisphere 2022 Influvac Tetra vaccine (AUST R 292237, Viatris Pty Ltd).

Eligible participants (n=150) will be randomised into the one of the following five treatment groups and will receive a single treatment of ID VXS-1222 (active), ID VXS 1222U (inactive), or IM Influvac Tetra (NH 2022/2023) (active comparator) on Day 1, as per their assigned group:
• Group 1: VXS-1222 (active), expected QIV delivered amount 21 µg (5 µg/strain) hemagglutinin (HA), n=35;
• Group 2: VXS-1222 (active), expected QIV delivered amount 42 µg (11 µg/strain) HA, n=35;
• Group 3: VXS-1222 (active), expected QIV delivered amount 70 µg (18 µg/strain) HA, n=35;
• Group 4: VXS-1222U (inactive), n=10;

Doses will be administered by a trained Study site team member. Training will be provided by the sponsor and documented in the study records.
Intervention code [1] 324356 0
Treatment: Devices
Intervention code [2] 324359 0
Prevention
Comparator / control treatment
Group 5: Influvac Tetra (NH 2022/2023) (active comparator), 60 µg (15µg per strain) HA, n=35 Intra muscular injection.
Control group
Active

Outcomes
Primary outcome [1] 332449 0
Safety and tolerability of Intradermal delivery (via HD-MAP) of VXS-1222 at 21 µg (5 µg per strain), 42 µg (11 µg per strain) and 70 µg (18 µg/strain) HA, compared to Intra muscular delivery of QIV at 60 µg (15µg per strain) HA and VXS-1222U (uncoated, vaccine free HD MAP).

Measured by:
Treatment site assessment of treatment site visibility, swelling or flaking assessed by clinical examination.
Any reported Adverse events.
There are no expected Adverse events other than localised skin responses to the HD-MAP or IM injection and these are listed in the Patient Information Form..
Timepoint [1] 332449 0
Days 4, 8, 22 and 57 post administration
Secondary outcome [1] 413554 0
the systemic immune response of ID delivery of VXS-1222 at 21 µg (5 µg per strain), 42 µg (11 µg per strain) and 70 µg (18 µg/strain) HA, compared to IM QIV at 60 µg (15µg per strain) HA and VXS-1222U (uncoated, vaccine free HD-MAP) determined by antibody titres from whole blood samples
Timepoint [1] 413554 0
Days 8, 22 and 57 post administration
Secondary outcome [2] 413555 0
skin penetration performance of applied HD MAPs at 21 µg (5 µg per strain), 42 µg (11 µg per strain) and 70 µg (18 µg/strain) HA

measured by scanning electron microscopy
Timepoint [2] 413555 0
immediately after administration and HD-MAP removal from skin

Eligibility
Key inclusion criteria
1) Aged 18 to 50 years (inclusive) at the time of consent;
2) Body mass index (BMI) within the range 18.0 to 32.0 kg/m² (inclusive) at Screening;
3) Being in good health, as determined by satisfactory medical history, physical examination, vital signs, laboratory evaluation and clinical judgment of the Investigator. Participants with stable, chronic underlying illnesses such as psychiatric/psychological disorders, hypertension, diabetes, ischemic heart disease or hypothyroidism (or other conditions as per investigator’s discretion) may be enrolled provided their signs and symptoms are controlled. If on regular prescription medication, the medication dose must have been stable for at least three months prior to Screening;
4) Adequate venous access in left or right arm to allow collection of a number of small-volume blood samples at different time points;
5) Women of childbearing potential must return a negative pregnancy test at Screening (serum) and pre-dose on Day 1 (urine), and must agree to remain sexually abstinent, use medically effective contraception or have a partner who is sterile or same-sex, from Screening through EoS. Post menopausal women can be included, and are defined as those with at least 12 months since their last menstrual period;
6) Non-surgically sterilised, sexually active male participants with a female partner of child-bearing potential must agree to use condoms, together with medically effective contraception for their female partner;
7) Participant is able to communicate effectively with study personnel and is considered likely to be reliable, willing and cooperative in terms of compliance with the protocol requirements;
8) Participant is able and willing to provide written, personally signed, informed consent to participate in the study.
Minimum age
18 Years
Maximum age
50 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1) Participants who have received a registered or investigational (confirmed active) influenza vaccination within the six months prior to Day 1;
2) Participants who have had laboratory-confirmed influenza infection within the six months prior to Day 1;
3) Participants with birthmarks, tattoos, wounds, scars, moles, blemishes, heavy hair or other skin conditions (such as eczema) at the planned vaccination site that could be expected to obscure the observation of application-site reactions;
4) Participant with known chronic spontaneous urticaria or dermographism;
5) Known predisposition to keloid-scar formation;
6) Known anaphylactic hypersensitivity to haemagglutinin or to any of the vaccine excipients (potassium chloride, potassium phosphate, sodium phosphate, sodium chloride, calcium chloride, magnesium chloride, sulfobutyl-ß-cyclodextrin) and to residues of eggs (ovalbumin, chicken proteins), formaldehyde, cetrimonium bromide, polysorbate 80, gentamicin, sodium citrate, sucrose, tylosine tartrate, or hydrocortisone;
7) Allergy to a previous vaccination at any time in the past;
8) Recent vaccination (within 30 days prior to Day 1) or any planned vaccination up to Day 22 with any non-influenza vaccine. In addition, any planned vaccination with influenza vaccine other than the study vaccines for the duration of the study;
9) Known history of demyelinating disease or Guillain-Barré syndrome;
10) History of granulomatous diseases, including sarcoidosis and granuloma annulare;
11) History of convulsions, epilepsy, other central nervous system diseases, excluding febrile convulsions experienced as a child that are considered resolved;
12) History of clinically significant haematological, gastrointestinal, hepatic, renal, cardiovascular, dermatological, immunological, respiratory, endocrine, oncological, neurological, metabolic, psychiatric disease, that, at the discretion of the Investigator, precludes the participant from the study;
13) Presence of active viral of bacterial infection, with or without fever (tympanic temperature greater than or equal to 38.0 °C), at Day 1 or within 72 hours prior to study vaccination, if determined by the Investigator to be of clinical significance. Participants with a minor illness such as mild diarrhoea or mild upper respiratory infection without fever may be enrolled at the discretion of the Investigator. Enrolment may be deferred for up to two weeks provided participant remains otherwise eligible and the total Screening period does not exceed 28 days;
14) History of any haematological malignancy or active neoplastic disease (excluding non-melanoma skin cancer that was successfully treated). Active is defined as having received treatment within the 5 years prior to Screening;
15) Presence of an active medical condition, defined as a condition under current evaluation or treatment, that is considered clinically significant by the Investigator, or a recent illness that is considered clinically significant by the Investigator;
16) Any condition that, in the opinion of the Investigator, is considered clinically significant or might interfere with the evaluation of the study objectives;
17) Planned surgery requiring a general anaesthetic, or surgery requiring inpatient hospitalisation for at least 24 hours during the entire study period.
18) History of illness and/or infection with Hepatitis B, or Hepatitis C or Human Immunodeficiency Virus (HIV), or a positive test for Hepatitis B surface antigen, Hepatitis C or antibodies against HIV at Screening;
19) History of abnormal bleeding, and/or thrombophlebitis unrelated to venepuncture or intravenous cannulation;
20) Receiving chronic treatment with immunosuppressive therapy, including chronic use (more than 14 continuous days) of systemic corticosteroids within 30 days prior to Day 1. Intraarticular, intrabursal, intraocular, intranasal, inhaled, or topical corticosteroids, within the dosage of the package insert and without any sign of systemic exposure, are permitted.
21) Participant who has received immunoglobulins and/or any blood or blood products within 3 months prior to Day 1 or plans to receive any blood or blood products at any time during the study.
22) Participant who has donated blood or plasma, or has had clinically significant blood loss, within 14 days prior to Day 1;
23) Female participant who is pregnant or breast-feeding, or intends to become pregnant, from Screening through EoS;
24) A history of alcohol or drug abuse in the past 12 months, or current declared alcohol consumption less than 4 standard drinks per day for 7 days per week (one standard drink is equivalent to 285 mL of full-strength beer, 100 mL of wine or 30 mL of spirits);
25) Use of any prescription medication (with the exception of contraceptives, hormone replacement therapy, or stable doses of medication required for the management of stable, chronic underlying illnesses) within seven days prior to Day 1;
26) Use of any investigational drug or device within 30 days, or five half-lives of the drug (whichever is longer) before Day 1;
27) Was a participant in a placebo-controlled influenza vaccine clinical trial within six months prior to Screening for this study, if the treatment arm is not known.
28) An employee, or a first-degree family member of an employee, of the Sponsor, Contract Research Organization conducting this study, or study site involved in this study.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Randomisation will be produced by the Statistician and the site Pharmacist will hold the allocation list. This will be unavailable/blinded to any other staff member working in the study.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
This will be a randomised, partially-blind, controlled study. VXS-1222 (active) and VXS 1223U (inactive) will be supplied to site as visually identical blinded (coded) product to maintain the blind of the study team and participant. Influvac Tetra (NH 2022/2023) (active comparator) is unable to be masked due to the nature of the product, and therefore the study team and participants will be aware of treatment assignment for this group.
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
The proposed sample size is 35 participants per active treatment group and 10 participants for the inactive group, totalling 150 participants overall. The sample size is consistent with monovalent data (A-H1N1) obtained from a previous Phase I study.

All data will be summarised by treatment group and time point
The general analytical approach for all data will be descriptive in nature:

Continuous variables:: Descriptive statistics will include the number of non-missing values, mean, standard deviation (SD), median, minimum, and maximum. The minimum and maximum values will be presented to the same number of decimal places as recorded in the raw data; mean, median and SD will be presented to one more decimal place than the raw data.
Categorical variables: Descriptive statistics will include frequency counts and percentages per category. Percentages will be rounded to one decimal place, with the denominator being the number of patients in the relevant population with non-missing data.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
12/11/2022
Actual
28/11/2022
Date of last participant enrolment
Anticipated
1/06/2023
Actual
17/04/2023
Date of last data collection
Anticipated
5/08/2023
Actual
9/06/2023
Sample size
Target
150
Accrual to date
Final
150
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 23095 0
University of Sunshine Coast Health Clinics - Sippy Downs
Recruitment hospital [2] 23096 0
University of the Sunshine Coast Clinical Trials Centre - Health Hub Morayfield - Morayfield
Recruitment postcode(s) [1] 38450 0
4556 - Sippy Downs
Recruitment postcode(s) [2] 38451 0
4506 - Morayfield

Funding & Sponsors
Funding source category [1] 312172 0
Commercial sector/Industry
Name [1] 312172 0
Vaxxas Pty Ltd
Country [1] 312172 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Vaxxas Pty Ltd
Address
37 Kent Street
Woolloongabba, QLD 4102
AUSTRALIA
Country
Australia
Secondary sponsor category [1] 313698 0
None
Name [1] 313698 0
Address [1] 313698 0
Country [1] 313698 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311558 0
Bellberry HREC
Ethics committee address [1] 311558 0
Ethics committee country [1] 311558 0
Australia
Date submitted for ethics approval [1] 311558 0
12/09/2022
Approval date [1] 311558 0
31/10/2022
Ethics approval number [1] 311558 0

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

Contacts
Principal investigator
Name 121534 0
Dr Nischal Sahai
Address 121534 0
University of the Sunshine Coast Clinical Trials Centre - Southbank
Building A1. SW 1 Complex
32 Cordelia Street
South Brisbane, QLD 4101
AUSTRALIA
Country 121534 0
Australia
Phone 121534 0
+61 07 5409 8630
Fax 121534 0
Email 121534 0
nsahai@usc.edu.au
Contact person for public queries
Name 121535 0
Angus Forster
Address 121535 0
Vaxxas Pty Ltd
37 Kent Street
Woolloongabba, QLD, 4102
AUSTRALIA
Country 121535 0
Australia
Phone 121535 0
+61 0734437838
Fax 121535 0
Email 121535 0
aforster@vaxxas.com
Contact person for scientific queries
Name 121536 0
Angus Forster
Address 121536 0
Vaxxas Pty Ltd
37 Kent Street
Woolloongabba, QLD, 4102
AUSTRALIA
Country 121536 0
Australia
Phone 121536 0
+61 0734437838
Fax 121536 0
Email 121536 0
aforster@vaxxas.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
the de-identified individual participant data will not be available for this study. Only the aggregate results of the full study cohort will be available as per the protocol.


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.