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Trial registered on ANZCTR


Registration number
ACTRN12615000583549
Ethics application status
Approved
Date submitted
18/05/2015
Date registered
3/06/2015
Date last updated
14/10/2015
Type of registration
Prospectively registered

Titles & IDs
Public title
A first-in-human study to evaluate the safety, tolerability and performance of uncoated and placebo-coated Nanopatches
Scientific title
A first-in-human study to evaluate the safety, tolerability and performance of uncoated and placebo-coated Nanopatches
Secondary ID [1] 286737 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Vaccination Delivery Device 295101 0
Condition category
Condition code
Other 295346 295346 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
Comparison of safety, tolerability and performance of uncoated and placebo coated Nanopatches and the Nanopatch applicator device (Vaccine Delivery Device).
The uncoated Nanopatch is a terminally sterilised 1cm2 monocrystalline silicon wafer with 8200 micro-projections.
The placebo-coated Nanopatch is a terminally sterilised 1 cm2 monocrystalline silicon wafer with 8200 micro-projections coated with hypromellose, trehalose dihydrate and phosphate buffered saline.
The Nanopatch delivery device is a hand-held mechanical, spring loaded and reusable applicator (CAP02) calibrated at a specific speed of either 20 m/s (placebo coated patch) or 17.5 m/s (uncoated patch).
There are 2 study cohorts; Patients in Cohort 1 on Day 0 will have one uncoated patch applied to the forearm and one uncoated patch applied to the deltoid. On Day 3 they will return to to the clinic and receive one placebo-coated patch to the forearm and one placebo-coated patch to the deltoid.
Cohort 2 will only receive placebo-coated patches on one occasion (Day 0). Two patches will be applied to the forearm and 2 patches willbe applied to the deltoid region. Therefore each subject will have a total of 4 patches applied, 2 to the forearm and 2 to the deltoid region of the non-dominant arm.
Each patch will be held on the arm for 2 minutes before manual removal.
Observations (and photography) will be done at regular timepoints on the day of application for then daily for 6 days, then again at the end of study visit.
Intervention code [1] 291892 0
Treatment: Devices
Comparator / control treatment
Uncoated nanopatches will be compared to placebo-coated nanopatches. Placebo coating consists of hypromellose, trehalose dihydrate and phosphate buffered saline.
Control group
Placebo

Outcomes
Primary outcome [1] 295098 0
Composite Primary Outcome: To examine the safety and tolerability of uncoated and placebo-coated Nanopatches in healthy volunteers. Safety is assessed by number of Adverse events; Tolerability assessed by observation and measurements of erythema, itching, induration and flaking of skin (Draize scoring system).
Timepoint [1] 295098 0
For Cohort 1; Observations will begin immediately after application for 2 hours then daily for 6 days after each application then on day 10, 14 and Day 35
For Cohort 2; Observations will begin immediately after application then daily for 6 days after application then on day 28
Secondary outcome [1] 314765 0
Composite outcome To assess the pain and acceptability of the Nanopatch administration process in healthy volunteers. This will be assessed by optional Questionnaire administered after application. (Study Specific design); Pain assessed on 100mm VAS.
Timepoint [1] 314765 0
Assessment will begin immediately after application and will continue for 2 hours.
Secondary outcome [2] 314888 0
To compare sites of application and uncoated versus placebo-coated patches within subjects. This will be assessed by examination and photography
Timepoint [2] 314888 0
For Cohort 1: examination and photography will be done on Days 0, 3, 7, 10, 14 and 35.
For Cohort 2: examination and photography will be done on Days 0, 3, 7, and 28.
Secondary outcome [3] 314889 0
Exploratory Objective: To perform post-application analysis of the nanopatches to investigate skin penetration and performance using scanning electron microscopy and for the placebo-coated nanopatches, residual trehalose content
Timepoint [3] 314889 0
The patches will be analysed post removal from patient.

Eligibility
Key inclusion criteria
1. Aged 18-45 years (inclusive).
2. Subject has a BMI within the range 18.0–30.0 kg/m2
3. Satisfactory medical assessment, with no clinically significant or relevant abnormalities in medical
history, physical examination, vital signs and laboratory evaluation (haematology or biochemistry)
4. Adequate venous access in their left or right arms to allow collection of a number of blood samples.
5. Subject is fair-skinned.
6. Subject is able to communicate effectively with study personnel and is considered reliable, willing and cooperative in terms of compliance with the protocol requirements.
7. Able and willing to provide written, personally signed and dated informed consent to participate in the study.
Minimum age
18 Years
Maximum age
45 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Subject with birthmarks, tattoos, wounds, scars, moles, blemishes, heavy hair or other skin conditions on both forearms and deltoid regions which could reasonably obscure application site reactions.
2. Known Predisposition to keloid scar formation.
3. History of clinically significant gastrointestinal, hepatic, renal, cardiovascular, dermatological, immunological, respiratory, endocrine, oncological, neurological, metabolic, psychiatric disease or haematological disorders.
4. History of malignancy, other than non-melanoma skin cancer.
5. An active medical condition that is under evaluation or treatment, or a recent illness, a chronic illness, an autoimmune disease or had major surgery within the last year.
6. History of Hepatitis B, Hepatitis C or HIV infection or clinical laboratory serology is positive for Hepatitis B surface antigen, Hepatitis C or HIV antibodies.
7. History of abnormal bleeding tendencies or thrombophlebitis unrelated to venepuncture or intravenous cannulation,
8. Receiving chronic treatment with immune-suppressive therapy (asthma inhalers and topical corticosteroids are permitted). All medications will be documented and reviewed for acceptance by the Investigator or a medically qualified nominee.
9. History of any psychiatric illness or psychological disorder which may impair the ability to provide written informed consent or participate in the study.
10. Subject has donated blood or plasma or clinically significant blood loss within 60 days prior to screening visit
11. Subject is pregnant or breast-feeding.
12. A history of alcohol or drug abuse in the last 12 months or current alcohol consumption is >4 standard drinks (or equivalent) per day.
13. Use of any prescription medication within 7 days, unless approved by the PI. All medications will be documented and reviewed for acceptance by the Investigator or a medically qualified nominee.
14. Use of any investigational drug or device within 30 days or 10 half-lives of the drug, whichever is longer, prior to the Day 0.

Study design
Purpose of the study
Prevention
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)
Subjects are placed into one of 2 cohorts, the placement into a cohort is dependent on the availability of the subject.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Cohort 1: 6 subjects receive an application of 2 uncoated Nanopatches (forearm and deltoid) and 7 days later receive an application of 2 placebo coated Nanopatches (forearm and deltoid) of the same arm.
Cohort 2: 12 subjects receive an application of 4 placebo-coated Nanopatches (2 patches per site: forearm and deltoid) to the same arm
Phase
Phase 1
Type of endpoint(s)
Safety
Statistical methods / analysis
No statistical testing is planned between the cohorts. Safety endpoints have been identified as being of main interest in this study. Study investigations will be exploratory and conclusions based on the complete set of subject evidence.
Mixed effects generalised linear models will be used to separately estimate variances between and within subjects and to make comparisons between sites of application and between uncoated and placebo coated patches for cohorts 1 and 2 separately.
Descriptive statistics of demographics (age, height and weight at screening, race and ethnic origin) will be presented by cohort group and overall. Medical history information collected at screening will be listed. All adverse events will be listed by subject and will include details of the onset date and time, duration, severity, causality and treatment/medications administered.
Laboratory parameters will be listed over the scheduled visits by subject number and treatment cohort. Vital signs (blood pressure, heart rate, aural temperature and respiratory rate) which are outside of the normal reference range and clinically significant will be tabulated .
Physical examination data will be tabulated.
Local reactions will be tabulated.
Concomitant medications will be coded to their generic name. All medications will be listed by subject, date and time of inset, end date and time, reason for administration.

Recruitment
Recruitment status
Completed
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 postcode(s) [1] 9692 0
4006 - Herston

Funding & Sponsors
Funding source category [1] 291289 0
Commercial sector/Industry
Name [1] 291289 0
Vaxxas Pty Ltd
Address [1] 291289 0
Suite 304, Level 3
1 Alfred Street
Sydney, New South Wales 2000
Country [1] 291289 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Vaxxas Pty Ltd
Address
Suite 304, Level 3
1 Alfred Street
Sydney, New South Wales 2000
Country
Australia
Secondary sponsor category [1] 289967 0
None
Name [1] 289967 0
Address [1] 289967 0
Country [1] 289967 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292859 0
QIMR - Berghofer Medical Research Institute Human Research Ethics Committee
Ethics committee address [1] 292859 0
QIMR locked Bag 2000
RBWH
Herston 4029
Ethics committee country [1] 292859 0
Australia
Date submitted for ethics approval [1] 292859 0
11/05/2015
Approval date [1] 292859 0
14/05/2015
Ethics approval number [1] 292859 0
P2104

Summary
Brief summary
This is a first in human study to evaluate the safety, tolerability and performance of a new vaccine delivery device.

The sponsor is developing a novel approach for the administration of vaccines that does not require the use of needles. Small nanopatches patches designed to carry the vaccine are applied to the skin and kept in place for 2 minutes. This study will assess how safe and acceptable these nanopatches are.
Trial website
www.noneedles.com.au
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 57354 0
Dr Paul Griffin
Address 57354 0
Q-Pharm Pty Ltd
Level 5, 300 Herston Road
Herston QLD 4006
Country 57354 0
Australia
Phone 57354 0
+61 (0)7 3845 3636
Fax 57354 0
Email 57354 0
qpharm@qpharm.com.au
Contact person for public queries
Name 57355 0
Dr Paul Griffin
Address 57355 0
Q-Pharm Pty Ltd
Level 5, 300 Herston Road
Herston QLD 4006
Country 57355 0
Australia
Phone 57355 0
+61 (0)7 3845 3636
Fax 57355 0
Email 57355 0
qpharm@qpharm.com.au
Contact person for scientific queries
Name 57356 0
Dr Angus Forster
Address 57356 0
Vaxxas Pty Ltd
Suite 304, Level 3
1 Alfred Street
NSW 2000
Australia
Country 57356 0
Australia
Phone 57356 0
+61 (0) 7 3346 3177
Fax 57356 0
Email 57356 0
aforster@vaxxas.com

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary