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Trial registered on ANZCTR


Registration number
ACTRN12621000820808
Ethics application status
Approved
Date submitted
6/04/2021
Date registered
28/06/2021
Date last updated
23/05/2022
Date data sharing statement initially provided
28/06/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
First-in-human study to investigate the skin tolerability of micro-projection array patches coated with live attenuated measles and rubella vaccine in healthy adult volunteers
Scientific title
Phase I clinical study with high-density microarray patches (HD-MAPs) coated with live attenuated measles and rubella vaccine (MR) in healthy adult volunteers
Secondary ID [1] 303874 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Measles infection 321953 0
Rubella Infection 322555 0
Condition category
Condition code
Infection 319209 319209 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
HD-MAP administration
HD-MAPs are approximately 1cm2. They are applied to the upper arm, over the deltoid muscle, preferably of the non-dominant arm of the participant. Following application, the HD-MAP is held in place for 60 seconds. Each HD-MAP is single use, disposable. Each participant will receive three HD-MAPs, once only in the following groups:

Group 1: 15 subjects receive (a) 1 active MR HD-MAP on the upper arm delivering ~2,000 CCID50 each of measles and rubella vaccine viruses AND (b) 2 placebo (uncoated) HD-MAPs.
Group 2: 15 subjects receive 3 active HD-MAPs on the upper arm, delivering a total of ~6,000 CCID50 each of measles and of rubella vaccine virus (as in group 1 each having ~2,000 CCID50 each virus per HD-MAP).
Group 3: 15 subjects receive three placebo uncoated HD-MAPs on the upper arm.
Intervention code [1] 320179 0
Treatment: Drugs
Intervention code [2] 320606 0
Treatment: Devices
Intervention code [3] 320607 0
Prevention
Comparator / control treatment
Group 4: 15 subjects receive 1 sub-cutaneous 0.5mL standard adult human dose MR injection to the upper arm (Serum Institute of India), with a label claim of not less than 1,000 CCID50 of each vaccine virus.
Control group
Active

Outcomes
Primary outcome [1] 327080 0
Safety of a single high and low-dose of live attenuated measles and rubella vaccine (MR, supplied by Serum Institute of India) delivered by the high-density microarray patch (HD-MAP), as MR HD-MAP, compared with an uncoated (placebo) HD-MAP and also subcutaneous (SC) administration of a standard adult human dose of a licensed MR vaccine, MR-Vac (Serum Institute of India) will be assessed using adverse events documented in accordance with the Common Terminology Criteria for Adverse Events (CTCAE4.0).
Timepoint [1] 327080 0
The number, severity and relatedness of local and systemic adverse events will be collected on the day of study product administration and daily until day 7 post-administration, then on days 14, 28 and 56 post administration.
For each subject the study duration is up to 56 days, accounting for all visits (excluding pre-treatment screening). If necessary, some subjects may be contacted at fortnightly intervals until treatment sites are no longer visible or have any other associated AEs.
Primary outcome [2] 327766 0
Incidence of treatment-emergent biochemical and hematological abnormalities as assessed by regional laboratory normal values for a given test.
Timepoint [2] 327766 0
The number, severity and relatedness of biochemical and hematological abnormalities will be assessed on day 7 and day 28 post-administration.
Secondary outcome [1] 393699 0
Measles serum neutralization antibody titers by plaque reduction neutralization (PRN) assay. Measles serum IgG antibody concentrations.
Timepoint [1] 393699 0
Days 7, 28 and 56 post vaccination
Secondary outcome [2] 393700 0
Rubella serum neutralization antibody titers by plaque reduction neutralization (PRN) assay. Rubella serum IgG antibody concentrations
Timepoint [2] 393700 0
Days 7, 28 and 56 post vaccination
Secondary outcome [3] 396518 0
Assessment of HD-MAP skin-penetration performance by scanning electron microscopy (SEM)
Timepoint [3] 396518 0
Post vaccine administration

Eligibility
Key inclusion criteria
Subjects must meet all of the following criteria to be eligible for participation in this study:
1. Aged 18–50 years (inclusive);
2. With a body mass index (BMI) within the range 18.0–32.0 kg/m²;
3. Satisfactory medical assessment: no clinically significant or relevant abnormalities in medical history, physical examination,
vital signs (blood pressure, oral temperature, heart rate, respiratory rate) and laboratory evaluation (haematology or biochemistry);
4. Adequate venous access in their left or right arms to allow collection of a number of small volume blood samples at different time points;
5. Risk of pregnancy: Females of childbearing potential should either be sexually inactive (abstinent) for 14 days prior to screening and throughout the duration of the study or be using one of the following acceptable birth control methods:
a. Surgically sterile (hysterectomy and/or bilateral oophorectomy);
b. Surgically sterile (bilateral tubal ligation with surgery at least six months prior to study initiation);
c. Intrauterine device (IUD) in place for at least three months;
d. Stable hormonal contraceptive for at least three months prior to study through completion of study;
e. Surgical sterilization (vasectomy) for female participant’s partner(s) at least six months prior to study;
f. Condom for male participant;
g. Menopausal women can be included, and are defined as being at least 12 months since their last menstrual period;
h. Females in same sex relationship can be included.
6. Subject 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;
7. Subject 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
Subjects meeting any of the following criteria will not be eligible for participation in this study:
1. Subject with birthmarks, tattoos, wounds, scars, moles, blemishes, heavy hair or other skin conditions (such as eczema) on upper arm regions (on both arms) that could be expected to obscure the observation of application-site reactions
2. Subject with known chronic spontaneous urticaria / dermographism;
3. Known anaphylactic hypersensitivity or allergy to a previous measles and/or rubella vaccination or to any of the vaccine components;
4. Recent vaccination (within 30 days prior to enrolment) with any vaccine or a plan to be vaccinated during the study period;
5. Vaccination with a measles- or rubella-containing vaccine in the past 5 years;
6. Receipt of blood, blood products, or immunoglobulins during the preceding three months;
7. Known predisposition to keloid-scar formation;
8. History of granulomatous diseases (especially sarcoidosis and granuloma annulare);
9. History of convulsions, epilepsy, other central nervous system diseases;
10. History of clinically significant hematological, gastrointestinal, hepatic, renal, cardiovascular, dermatological, immunological, respiratory, endocrine, oncological, neurological, metabolic, psychiatric disease;
11. An acute febrile illness at the time of enrolment;
12. A clinically significant history of cancer;
13. An active medical condition that is considered clinically significant and is under evaluation or treatment;
14. A recent illness that is considered clinically significant;
15. A chronic illness that is considered clinically significant such as an autoimmune disease;
16. A history of major surgery that is considered clinically significant, for example within the past year;
17. History of illness and/or infection with hepatitis B, or hepatitis C or HIV, or, during screening, a positive test for Hepatitis B surface antigen, Hepatitis C or antibodies against HIV.
18. History of abnormal bleeding, and/or thrombophlebitis unrelated to venepuncture or intravenous cannulation;
19. Receiving chronic treatment with immune-suppressive therapy other than asthma inhalers and topical corticosteroids. All such medications will be documented and reviewed for acceptance by the investigator or other medically qualified nominee;
20. History of any psychiatric illness or psychological disorder that might impair the ability to provide written informed consent or participate in the study;
21. Subject has donated blood or plasma or has had clinically significant blood loss within 60 days before the first screening visit;
22. Subject is pregnant or breast-feeding;
23. A history of alcohol or drug abuse in the past 12 months, or current declared alcohol consumption is >4 standard drinks (equivalent to 7 units) per day;
24. Use of any prescription medication (except for contraceptives and Hormone Replacement Therapy (HRT)) within seven days of enrolment, unless approved by the principal investigator. All medications will be documented and reviewed for acceptance by the investigator or other medically qualified nominee
25. Use of any investigational drug or device within 30 days, or 5 half-lives of the drug (whichever is longer), before the Day 0 of the 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)
Allocation concealed by sealed envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created
by computer software
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
Phase
Phase 1
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
19/07/2021
Actual
1/08/2021
Date of last participant enrolment
Anticipated
3/09/2021
Actual
1/02/2022
Date of last data collection
Anticipated
29/10/2021
Actual
30/04/2022
Sample size
Target
60
Accrual to date
Final
60
Recruitment in Australia
Recruitment state(s)
QLD

Funding & Sponsors
Funding source category [1] 308269 0
Charities/Societies/Foundations
Name [1] 308269 0
Bill and Melinda Gates Foundation
Country [1] 308269 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Vaxxas Pty Ltd
Address
Suite 13.02,
Level 13,
179 Elizabeth Street,
Sydney,
NSW 2000
Country
Australia
Secondary sponsor category [1] 309065 0
None
Name [1] 309065 0
None
Address [1] 309065 0
None
Country [1] 309065 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308245 0
Bellberry Limited
Ethics committee address [1] 308245 0
123 Glen Osmond Rd, Eastwood SA 5063
Ethics committee country [1] 308245 0
Australia
Date submitted for ethics approval [1] 308245 0
03/02/2021
Approval date [1] 308245 0
16/04/2021
Ethics approval number [1] 308245 0

Summary
Brief summary
This study is designed to test the hypothesis that HD-MAP application to the skin using a small number of healthy adult subjects with a well characterised measles rubella (MR) vaccine results in comparable safety / local skin reaction to conventional subcutaneous vaccination. This study represents the first time that HD-MAPs with an active measles rubella vaccine will be applied to humans. Therefore, this study will assess both systemic and the local reaction to application of the MR HD-MAPs delivering a low and high doses measles and rubella vaccine virus, in comparison to uncoated MAPs, and SC administration of the standard adult human dose of MR vaccine (Serum Institute of India). The local skin response will be monitored for up to 56 days. On-site clinic assessments will be performed up to 2 hours post application and at day 3, 7, 28 and 56 days post application. Phone calls will be made at Day 1 and Day 14
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 110054 0
Dr Angus Forster
Address 110054 0
Vaxxas Pty Ltd
Translational Research Institute
37 Kent Street
Woolloongabba,
QLD 4102
Country 110054 0
Australia
Phone 110054 0
+61 7 3443 7838
Fax 110054 0
Email 110054 0
[email protected]
Contact person for public queries
Name 110055 0
Angus Forster
Address 110055 0
Vaxxas Pty Ltd
Translational Research Institute
37 Kent Street
Woolloongabba,
QLD 4102
Country 110055 0
Australia
Phone 110055 0
+61 7 3443 7838
Fax 110055 0
Email 110055 0
[email protected]
Contact person for scientific queries
Name 110056 0
Angus Forster
Address 110056 0
Vaxxas Pty Ltd
Translational Research Institute
37 Kent Street
Woolloongabba,
QLD 4102
Country 110056 0
Australia
Phone 110056 0
+61 7 3443 7838
Fax 110056 0
Email 110056 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

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
Dimensions AIAccelerating the Development of Measles and Rubella Microarray Patches to Eliminate Measles and Rubella: Recent Progress, Remaining Challenges2022https://doi.org/10.3389/fpubh.2022.809675
EmbaseSafety, Tolerability, and Immunogenicity of Measles and Rubella Vaccine Delivered with a High-Density Microarray Patch: Results from a Randomized, Partially Double-Blinded, Placebo-Controlled Phase I Clinical Trial.2023https://dx.doi.org/10.3390/vaccines11111725
Dimensions AIEstimating the future global dose demand for measles–rubella microarray patches2023https://doi.org/10.3389/fpubh.2022.1037157
N.B. These documents automatically identified may not have been verified by the study sponsor.