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Trial registered on ANZCTR


Registration number
ACTRN12623000837628
Ethics application status
Approved
Date submitted
7/06/2023
Date registered
4/08/2023
Date last updated
4/08/2023
Date data sharing statement initially provided
4/08/2023
Type of registration
Retrospectively registered

Titles & IDs
Public title
The test evaluation, development and implementation (TEDI) study recruits asymptomatic individuals to provide negative clinical samples with the purpose of developing and validating new point-of-care of diagnostic tests for a range of infectious diseases.
Scientific title
The test evaluation, development and implementation (TEDI) study recruits asymptomatic individuals to provide negative clinical samples with the purpose of developing and validating new point-of-care of diagnostic tests for a range of infectious diseases.
Secondary ID [1] 309817 0
None
Universal Trial Number (UTN)
Trial acronym
TEDI study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
COVID-19
 330234 0
RSV 330413 0
Dengue 330414 0
Hepatitis B 330415 0
gonorrhoea 330416 0
measles 330417 0
Influenza 330646 0
Zika 330647 0
Japanese encephalitis 330648 0
Ross River virus 330649 0
chikungunya 330650 0
Malaria 330651 0
Hepatitis C 330652 0
HIV 330653 0
chlamydia 330654 0
monkeypox 330655 0
tetanus 330656 0
Condition category
Condition code
Infection 327105 327105 0 0
Other infectious diseases

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Description of intervention(s) / exposure: This is a prospective study to obtain fresh samples from staff, patients, and visitors at Royal Melbourne Hospital, as well as members of the general public via social media.

• Recruitment and sampling: Victorian Infectious Diseases Service (outpatient clinic), Royal Melbourne Hospital, 300 Grattan St, Parkville, VIC.
• Research and Development: ZiP Diagnostics Pty Ltd, 24 Cromwell St, Collingwood Victoria, Australia

Participant recruitment: A general advertising email will be sent to employees at RMH, as well as posters displayed in common areas around the hospital to invite patients and visitors to participate. For RMH employees, the email will be sent via Heads of Department/Nurse Unit Managers. Members of the general public will be invited to participate through social media advertising. Advertisements include a website address that contains additional information regarding the study, participation involvement and contact details. Potential study participants will be able to make an individual teleconference appointment to discuss the details of the study with the Principal Investigator (PI) or Research Nurse (RN). In addition to recruiting new participants, those who completed the first 12 months of the study will be approached by the RN to ascertain whether they would be interested in reconsenting to the 12-month study extension.
Participant consent processes: Individual information sessions will be via teleconference with interested potential participants. The RN will provide potential study participants with a copy of the Patient Informed Consent Form (PICF) and additional verbal information about the study. If a potential participant agrees to participate, they will be asked to sign the PICF which will be posted out to them and returned to the RN by mail in a reply-paid envelope. Once written informed consent is provided the RN will assign the participant a unique Participant Identification (PID) Number. A copy of the PICF will be given to the participants to keep.

Sample size and frequency of recruitment: Up to 70 participants will be recruited. This potentially offers a diverse range of specimen types and heterogenous samples that can be collected. The specimen type and sampling frequency will be according to the experimental needs of the projects. The total study duration will be 24, months. As critical experiments are planned, the ZiP Diagnostics contact person will inform the Site Coordinator (SC) about the number and type of samples required.

Sample types:
Self-collected samples: nasal swabs, throat swabs, nose and throat swabs, skin swabs, saliva, urine, vaginal swabs. These samples are self-collected by participants based on standard operating procedures (SOPs).
Nurse-collected samples: blood (venous or fingerprick). Blood samples are collected by trained RN according to the standard operating procedures (SOPs) developed that outlined in study protocol.

Sample collection: The study is likely to have variable needs for clinical samples because the test development program is dynamic. To ensure that samples are only collected as required for specific experiments, the R&D team (via the ZiP Diagnostics Study Coordinator) will request the specific specimen types and numbers of samples on a weekly basis. This will allow the SC to email all study participants to request samples, with a minimum of 24 hours’ notice. Participants that are available and willing to donate samples on that occasion will nominate an approximate time for sample self-collection or make an appointment to provide blood samples with the RN. All urine, swab and saliva samples will be self-collected by participants following the sample collection standard operating procedure (SOP) developed as outlined in the study protocol. Due to the current COVID-19 outbreak, participants that are no longer at RMH will be able to take a self-collected sample at home.
Participants will be given a self-collection kit by the RN or it may be couriered to them. If a venous or fingerprick blood sample is required, this will be taken by a trained Registered Nurse at the RMH clinic. The RN is trained to collect blood samples according to the sample collection standard operating procedures (SOPs) developed as outlined in the study protocol at the RMH clinic. The RN collects The RN When self-collected samples have been obtained, they will be returned by the participant to the RN, who will contact the courier and inform the ZiP Diagnostics Study Coordinator that a sample will be delivered. Samples collected at home will be couriered directly to the ZiP Diagnostics lab.
Each sample is assigned a unique and coded Sample Identification (ID) Number, based on the PID, date the sample was taken and sample type. This will be entered into the laboratory sample log by the Zip Diagnostic Study Coordinator. At no stage will any R&D staff have access to information about the study participants, or access to re-identifiable or decoded data that would disclose the identity of participants.

To illustrate how the sample collection process will occur; the Chlamydia trachomatis and Neisseria gonorrhoeae (CT/NG) project may require 3 urine and vaginal samples for a particular experiment, and this experiment might be repeated a second time in the same week. This sample requirement could successfully be met either with 3 people donating twice in that week, or 6 participants donating once. It is likely that over the 12 months of the study, there will be many weeks in which no clinical samples will be required. Study participants may choose to donate one sample type but refuse to provide another sample type. For example, if a request is made for 3 nasal swabs for the SARS-CoV-2 project and 3 urine/ vaginal swab samples for the CT/NG project, then one participant might choose to provide all sample types, but another participant might choose to provide a urine sample but decline to provide a nasal or vaginal swab. This will be at the discretion of the study participant. Participant preferences and the number and frequency of sampling will be managed by the SC. Participants can choose the number and frequency of the sampling.
Participants may be asked to provide 2 of the same sample type on the same day for clinical validation testing. On these occasions, one sample will be sent to a NATA-accredited diagnostic laboratory and the other will be used at ZiP Diagnostics. Both test outcomes are expected to be negative. These comparative test results assist in the clinical validation of the test platform demonstrating the new test accurately determines negative test results by comparing them to gold-standard laboratory-based tests.

A maximum number of samples is defined to ensure that there is not an excessive burden placed on any of the study participants. Participants can provide samples at each request from the SC or choose to refuse to provide a sample at any time point.

The following collection limits will be applied:

- Up to but not exceeding 2 nasal swabs per person per day, max limit of three times a week. Mid-turbinate swabs are preferred but anterior nares may also be tested. Deep nasopharyngeal swabs will not be collected.
- Up to but not exceeding 2 throat swabs per person per day, max limit of three times a week.
- Up to but not exceeding 2 throat and nose swabs per day, max limit of three times a week.
- Up to but not exceeding 2 skin swabs per person per day, max limit of three times a week.
- Up to but not exceeding 20ml saliva per person per day, max limit of three times a week.
- Up to but not exceeding 2 vaginal swabs per person per day, max limit of three times a week.
- Up to but not exceeding 200mL of urine per person per day, max limit of three times a week.
- Up to but not exceeding 20mL of blood per person per day, max limit of once per week.

OUTCOME MEASURES
Samples collected in this study will be used to optimise sample processing methods, reagent composition, and result algorithms, and to ascertain early insights into test performance including sensitivity, specificity, and reproducibility for the new point-of-care for a range of infectious diseases.
A subset of samples will be used as negative controls for clinical validation purposes (determine sensitivity and specificity.)
The point-of-care diagnostic tests are based on DNA/ RNA nucleic acid amplification, as well as lateral flow antigen/ antibody detection methods.
These tests are for a range of infectious diseases including respiratory pathogens (SARS-CoV-2, Influenza, RSV,) mosquito-borne diseases (Dengue, Zika, Japanese encephalitis, chikungunya, Ross River virus, Malaria), Blood-borne viruses (e.g., Hepatitis B, Hepatitis C, HIV), Sexually Transmitted Diseases (e.g., gonorrhoea, chlamydia, monkeypox, etc), Vaccine-preventable diseases (measles, tetanus, etc).

Current Project:
Ethics and governance approval was first obtained for the TEDI study on 14 October 2021. Since that time, negative samples have been collected for the purposes of optimising a new SARS-CoV-2 point-of-care test, called ZiP-CoVx-P2. We recently obtained an ethics amendment to use these samples to validate this SARS-CoV-2 test, comparing it to lab-based RT-PCR.
Primary Objective: To optimise novel diagnostic tests for different infectious diseases. This will use a range of negative human specimen types as a clinical matrix with spiked-in microorganisms.
Secondary Objective: To undertake analytical test performance testing in early-stage validation studies using mock-infected human samples. Early-stage analytical validation in alpha and beta prototypes will guide design and manufacture revisions to ensure optimal performance. This is to ensure that final analytical testing and clinical trials using final ‘lock-down’ products are likely to meet performance criteria.
Sample type: combined oropharyngeal (throat) and bilateral mid-turbinate (nasal) swabs.
Comparator: established RT-PCR standard platform.
Outcome:
1) Develop an optimised point-of-care test that meets pre-specified test specifications.
2) Determine test sensitivity and specificity (including limit-of-detection and clinical sensitivity/ specificity, compared with lab-based RT-PCR) using 100 positive and 500 negative samples.
Intervention code [1] 326252 0
Diagnosis / Prognosis
Comparator / control treatment
The paired sample will be used for gold-standard comparator test methods run in a laboratory.
For example,
• Laboratory-based reverse transcriptase polymerase chain reaction (RT-qPCR) analysis will be used as the gold-standard comparator for respiratory pathogens (SARS-CoV-2, Influenza, RSV), mosquito-borne diseases (Dengue, Zika, Japanese encephalitis, chikungunya, Ross River virus, Malaria), Blood-borne viruses (e.g. Hepatitis B, Hepatitis C, HIV), Sexually transmitted Diseases (e.g., gonorrhoea, chlamydia, monkeypox, etc), Vaccine-preventable diseases (measles, tetanus, etc.
• Enzyme immunoassays (EIAs) will be used as the gold-standard comparator for point-of-care tests for responses against vaccine-preventable pathogens (e.g., measles, tetanus).
• Thick and thin blood film examination for malaria parasites by light microscopy will be used as the gold-standard comparator for Malaria.
Control group
Active

Outcomes
Primary outcome [1] 334969 0
Develop an optimised point-of-care test that meets pre-specified test specifications.
Timepoint [1] 334969 0
Cumulative samples will be assessed at a single timepoint that will occur when all negative samples have been collected. Samples will be stored at or below -20oC until tested.
Primary outcome [2] 335339 0
Determine the sensitivity and specificity of a new diagnostic test “ZiP-CoVx-P2 test” for COVID-19 compared to laboratory-based polymerase chain reaction (PCR) analysis as the gold-standard comparator
Timepoint [2] 335339 0
Cumulative samples will be assessed at a single timepoint that will occur when all negative samples have been collected. Samples will be stored at or below -20oC until tested.
Secondary outcome [1] 425106 0
None
Timepoint [1] 425106 0
None

Eligibility
Key inclusion criteria
Written informed consent is provided.
Age: 18 years years and older
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
None

Study design
Purpose
Screening
Duration
Cross-sectional
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
When a subset of samples is used as negative controls for clinical validation purposes for the new POC diagnostic test platform. Then, sensitivity and specificity are estimated against gold-standard comparator test methods.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
30/11/2021
Date of last participant enrolment
Anticipated
17/03/2024
Actual
Date of last data collection
Anticipated
17/03/2024
Actual
Sample size
Target
70
Accrual to date
45
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 24853 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment postcode(s) [1] 40502 0
3050 - Parkville

Funding & Sponsors
Funding source category [1] 314002 0
Commercial sector/Industry
Name [1] 314002 0
ZiP Diagnostics Pty Ltd
Country [1] 314002 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
ZiP Diagnostics Pty Ltd
Address
24 Cromwell Street, Collingwood, Vic 3066
Country
Australia
Secondary sponsor category [1] 315887 0
None
Name [1] 315887 0
Address [1] 315887 0
Country [1] 315887 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 313140 0
Royal Melbourne Hospital Human Research Ethics Committee
Ethics committee address [1] 313140 0
Office for Research
The Royal Melbourne Hospital
Level 2 South West
300 Grattan Street
Parkville VIC 3050
Australia
Ethics committee country [1] 313140 0
Australia
Date submitted for ethics approval [1] 313140 0
20/11/2020
Approval date [1] 313140 0
19/08/2021
Ethics approval number [1] 313140 0
HREC Reference Number: HREC/71883/MH-2020

Summary
Brief summary
This is a prospective study to collect different human specimen types to be used in the test development, optimisation, analytical validation and clinical validation of new diagnostic tests for a range of infectious diseases.
Primary Objectives: To optimise novel diagnostic tests for different infectious diseases. This will use a range of negative human specimen types as a clinical matrix with spiked-in microorganisms.
Secondary Objectives: To undertake analytical test performance testing in early-stage validation studies using mock-infected human samples.
Tertiary Objectives: To undertake clinical validation using the samples provided as negative controls.
Investigational products: The sample obtained from this study are used in the test development, optimisation, analytical validation and clinical validation of new diagnostic tests for a range of infectious diseases.
The point-of-care diagnostic tests are based on DNA/ RNA nucleic acid amplification, as well as lateral flow antigen/ antibody detection methods.
These tests are for a range of infectious diseases including respiratory pathogens (e.g., SARS-CoV-2, influenza, tuberculosis), sexually transmitted infections, viral hepatitis (e.g., Hepatitis B, Hepatitis C), insect-borne disease (e.g., dengue, malaria), infectious viral diseases (e.g., monkeypox), and vaccine-preventable diseases (measles, tetanus).
Comparator: The other sample will be used for gold-standard comparator test methods run in a laboratory. For example, laboratory-based RT-qPCR analysis, and serological assays (ELISA, IFA, CFA, agglutination assay, western blot).
Outcome Measures: Samples obtained in this study will be used as a clinical matrix to optimise sample processing methods, reagent composition, result algorithms, and to ascertain early insights into test performance including sensitivity, specificity, and reproducibility.
A subset of samples will be used as negative controls for clinical validation purposes, to estimate sensitivity and specificity.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 127126 0
A/Prof Joe Sasadeusz
Address 127126 0
Victorian Infectious Diseases Service Outpatient Department
Address: 300 Grattan st, Parkville, Vic 3050
Country 127126 0
Australia
Phone 127126 0
+61 3 9342 7200
Fax 127126 0
Email 127126 0
[email protected]
Contact person for public queries
Name 127127 0
Jonathan (Jack) Richards
Address 127127 0
ZiP diagnostics Pty Ltd, 24 Cromwell Street, Collingwood, Vic 3066, Australia
Country 127127 0
Australia
Phone 127127 0
+61 03 8414 5770
Fax 127127 0
Email 127127 0
[email protected]
Contact person for scientific queries
Name 127128 0
Jonathan (Jack) Richards
Address 127128 0
ZiP diagnostics Pty Ltd, 24 Cromwell Street, Collingwood, Vic 3066, Australia
Country 127128 0
Australia
Phone 127128 0
+61 03 8414 5770
Fax 127128 0
Email 127128 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
No additional documents have been identified.