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Trial registered on ANZCTR


Registration number
ACTRN12623000947606
Ethics application status
Approved
Date submitted
7/08/2023
Date registered
1/09/2023
Date last updated
11/08/2024
Date data sharing statement initially provided
1/09/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
A clinical trial to study the safety and immunogenecity (“the ability of a molecule or substance to provoke an immune response”) of Varicella zoster virus vaccine in healthy male and female adults
Scientific title
A Single-center, Randomized, Double-blind, Placebo- and Positive-controlled Phase I Study to Evaluate the Safety, Tolerability, and Immunogenicity of Recombinant Zoster Vaccine (CHO) in Healthy Adults
Secondary ID [1] 310005 0
TVAX-006-01
Universal Trial Number (UTN)
U1111-1294-3628
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Varicella-zoster Virus 330506 0
Condition category
Condition code
Infection 327350 327350 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Arm 1 Low dose adjuvant + antigen group: 0.5 mL/vial, administered 0.5 mL intramuscular injection per vaccination on Day 1 and Day 61. Containing 50 µg of Varicella-zoster Virus Glycoprotein E (VZV-gE) antigen, along with half-dose adjuvant system TVA01: 25 µg of Quillaja saponaria Molina, fraction 21 (QS-21), 250 µg of cytosine-phosphate-guanine Oligodeoxynucleotides (CpG ODN).

Arm 2 high dose adjuvant + antigen group: 0.5 mL/vial, administered 0.5 mL intramuscular injection per vaccination on Day 1 and Day 61. Containing 50 µg of Varicella-zoster Virus Glycoprotein E (VZV-gE) antigen, along with half-dose adjuvant system TVA01: 50 µg of Quillaja saponaria Molina, fraction 21 (QS-21,500) µg of cytosine-phosphate-guanine Oligodeoxynucleotides (CpG ODN).

Arm 3 Low dose adjuvant group: 0.5 mL/vial, administered 0.5 mL intramuscular injection per vaccination on Day 1 and Day 61. Containing half-dose adjuvant system TVA01: 25 µg of Quillaja saponaria Molina, fraction 21 (QS-21), 250 µg of cytosine-phosphate-guanine Oligodeoxynucleotides (CpG ODN).

Arm 4 high dose adjuvant group: 0.5 mL/vial, administered 0.5 mL intramuscular injection per vaccination on Day 1 and Day 61. Containing adjuvant system TVA01: 50 µg of Quillaja saponaria Molina, fraction 21 (QS-21), 500 µg of cytosine-phosphate-guanine Oligodeoxynucleotides (CpG ODN).

A registered nurse will administer the injections to participants. The nurse will record the time of injection in trial notes and if it's completed or interrupted. Other staff can assess clinic notes for any indications of medication non-adherence.
Intervention code [1] 326452 0
Prevention
Comparator / control treatment
Arm 5 placebo group: 0.5 mL/vial, administered 0.5 mL intramuscular injection per vaccination on Day 1 and Day 61. Containing normal saline.

Arm 6 positive control group: 0.5 mL/vial, administered 0.5 mL intramuscular injection per vaccination on Day 1 and Day 61. Containing 50 µg of Varicella-zoster Virus Glycoprotein E (VZV-gE) antigen.
Control group
Active

Outcomes
Primary outcome [1] 335564 0
To assess the safety and tolerability of recombinant zoster vaccine (Chinese hamster ovary, CHO) in healthy adults.
Timepoint [1] 335564 0
Vital signs (blood pressure, pulse rate, axillary temperature and respiration rate in the sitting position) will be collected within 28 days prior to the first dose, on the day of first dose, day 4, day 8, day 31 after the first dose, on the day of second dose, day 4, day 8, day 31 after the second dose, 8 months after the first dose, or 7 days after the early termination.
Per protocol Blood Pressure, Pulse Rate, Temperature and Respiratory Rate will be recorded. Vitals signs are monitored utilizing automated vital signs monitor such as the Welch Allyn Vital Signs Monitor 6000 Series. Temperature is recorded using a Tympanic thermometer.

Physical exam will be performed within 28 days prior to the first dose, within 7 days prior to the first dose or on the day of first dose, day 4, day 8, day 31 after the first dose, within 7 days prior to the second dose or on the day of second dose, day 4, day 8, day 31 after the second dose, 8 months after the first dose, or 7 days after the early termination.

Routine blood test, blood chemistry, blood coagulation tests and routine urine tests will be done within 28 days prior to the first dose, within 7 days prior to the first dose or on the day of first dose, day 4, day 31 after the first dose, within 7 days prior to the second dose or on the day of second dose, day 4 after the second dose, or 7 days after the early termination.

AE/SAE/AESI will be collected on the day of first dose, day 4, day 8, day 31 after the first dose, on the day of second dose, day 4, day 8, day 31 after the second dose, or 7 days after the early termination. Example of possible AEs are immune-mediated diseases (including rheumatic polymyalgia, rheumatoid arthritis, psoriasis, autoimmune thyroiditis, Sjogren's syndrome, etc.); and neurological events (including acute demyelinating encephalomyelitis and transverse myelitis). AEs may be obtained by spontaneous reporting or by publicly asking, examining, or assessing participants, or from patient diary and other medical records.
Secondary outcome [1] 424965 0
To preliminarily evaluate the immunogenicity of recombinant zoster vaccine (CHO).
Timepoint [1] 424965 0
Cellular immunity test and Humoral immunity test will be done on the day of first dose, day 31 after the first dose, on the day of second dose, day 31 after the second dose, 8 months after the first dose, or 7 days after the early termination. These will be assessed as composite secondary outcome.

Eligibility
Key inclusion criteria
1) Healthy men or women aged 30 to 70 years.
2) Able to fully understand and voluntarily sign the informed consent form ICF.
3) Able to comply with the requirements for the clinical research protocol to complete the trial.
4) Females of childbearing potential must agree not to become pregnant from signing the ICF and through 6 months after the last vaccination. Men and women of childbearing potential must agree to use contraception from signing the ICF and through 6 months after the last vaccination
OR be defined as not of childbearing potential
5). Female subjects of childbearing potential, must have a negative pregnancy test at screening, and negative urine pregnancy test at D1, and are not lactating and agree not to breastfeed up to 6 months post full vaccination.
6). Male participants must be vasectomized or agree to wear a condom during intercourse with a women of child bearing potential (WOCBP). Male participants must inform their female partners who are WOCBP of the contraceptive requirements of the protocol and are expected to adhere to using contraception with their partner.
Minimum age
30 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Exclusion criteria for first dose
1) A history of herpes zoster.
2) Subject has received any varicella zoster vaccine or herpes zoster vaccine or planning to take those vaccines during the study.
3) Any clinically significant allergic history, including to any vaccine or vaccine-related component, such as urticaria, difficulty breathing, or angioneurotic edema, or any clinically significant allergic reactions.
4) Received any immunosuppressive therapy (e.g. long-term application of systemic glucocorticoids greater than or equal to 14 days, with dose greater than or equal to 2 mg/kg/day or greater than or equal to 20 mg/day of prednisone or equivalent dose of prednisone dose) within 3 months before dosing (excluding administration of inhaled, intra-articular, and topical steroids); receipt of whole blood or blood products within 3 months before vaccination or plan to use them during the study period.
5) Previous vaccination with any vaccine within 30 days before each vaccination or planning to take any vaccine 30 days after each vaccination.
6) History of convulsions, epilepsy, encephalopathy (e.g. congenital cerebral hypoplasia, brain trauma, brain tumor, cerebral hemorrhage, cerebral infarction, brain infection, cerebral nerve tissue damage caused by chemical drug poisoning, etc.); clinically significant history of psychiatric disease or family history of bipolar disorder, schizophrenia.
7) History of malignancy [excluding basal cell carcinomas (BCC) and squamous cell carcinomas (SCC)] within 5 years prior to randomization
8) Asplenia or functional asplenia, or splenectomy caused by any circumstances.
9) Presence of primary or secondary immunodeficiencies or have been diagnosed with congenital or acquired immunodeficiency, infection, lymphoma, leukemia, systemic lupus erythematosus (SLE), rheumatoid arthritis, juvenile rheumatoid arthritis (JRA), inflammatory bowel disease (IBD), or other autoimmune disease.
10) Has severe cardiovascular diseases (pulmonary heart disease, pulmonary edema), severe liver or renal diseases, chronic obstructive pulmonary; uncontrolled diabetes [hemoglobin A1c (HbA1c) >9.0%].
11) History of thrombocytopenia or other coagulation disorders which may be contraindications for an intramuscular injection.
12) Abnormal blood pressure in sitting position at any time points during screening and before the first vaccination (systolic pressure greater than or equal to 145 mmHg and/or diastolic pressure greater than or equal to 95 mmHg).
13) History of fever within 3 days before the first dose (tympanic temperature greater than 37.5 degree celsius) or have suffered acute diseases requiring systemic application of antibiotics or antiviral therapy or in the acute phase of chronic infection within 7 days before vaccination.
14) Any laboratory values out-of-range at the investigator’s discretion, or with clinical significance as judged by the investigator.
16) Positive serology test results for hepatitis C virus antibody (HCV Ab), human immunodeficiency virus (HIV) antibody, syphilis treponema pallidum (S-TP) antibody, Hepatitis B core antibody (HBcAb) or hepatitis B virus surface antigen (HBsAg) test at screening.
17) Those who have a history of alcoholism or excessive drinking (14 units/week for female and 21 units/week for male. 1 unit = 285 mL beer, or 25 mL liquor, or 100 mL wine) within 6 months prior to dosing or have a positive result in alcohol breath test.
18) Subject does not have one suitable injection site (deltoid muscle of either arm) due to any conditions that are judged by the investigator to be unsuitable for intramuscular injection, such as tattoo/scars, ulceration, etc..
19) Received any investigational drugs or vaccines within 30 days before vaccination.
20) Donation of plasma within 7 days prior to dosing. Donation or loss of blood (excluding volume drawn at screening) of 50 mL to 499 mL of blood within 30 days, or more than 499 mL within 56 days prior to the first dosing.
21) Received anticoagulants including aspirin within 15 days or the first vaccination planning to take such drugs from the first vaccination to 6 weeks after the full vaccination.
22) Any reason which, in the opinion of the investigator, would interfere with the study objectives or the safety of participants, including but not limited to subject is judged to be unlikely to complete the protocol for any reason.
Exclusion criteria for second dose
1) Participants who meet the exclusion criteria for the first dose after receiving the first dose, as determined by the investigator, will not be eligible to continue participating in the study.
2) Participants who experience a serious adverse reaction (SAR) after receiving the first dose, as determined by the investigator, will not be eligible to continue participating in the study.
3) Participants who experience a severe allergic reaction after receiving the first dose, as determined by the investigator, will not be eligible to continue participating in the study.
4) Any other factors judged by investigator that are not suitable for the participants to continue 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)
sealed opaque 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 (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
Intervention assignment
Parallel
Other design features
The study will be conducted in two parts: Part 1 will include a younger healthy adult population aged = 30 - < 50 years and Part 2 will include an older healthy adult population aged = 50 - = 70 years. Each part will consist of 2 cohorts (low dose and high dose) and each cohort will consist of 3 groups (adjuvant group, adjuvant+antigen group and control group).
Phase
Not Applicable
Type of endpoint/s
Safety
Statistical methods / analysis
SAS version 9.4 or above (SAS Institute Inc. SAS/STAT, Cary, NC, US). will be used for statistical analysis.
All variables will be analyzed descriptively with appropriate statistical methods: categorical variables by frequency tables and continuous variables by descriptive statistics (i.e., number of patients, mean, standard deviation, minimum, median, and maximum). Unless otherwise specified, no imputation of missing information will be applied. No formal statistical test is planned.

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
2/10/2023
Actual
9/11/2023
Date of last participant enrolment
Anticipated
29/03/2024
Actual
3/05/2024
Date of last data collection
Anticipated
27/12/2024
Actual
Sample size
Target
100
Accrual to date
Final
100
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 25347 0
Nucleus Network Brisbane Clinic - Herston
Recruitment postcode(s) [1] 41056 0
4006 - Herston

Funding & Sponsors
Funding source category [1] 314182 0
Commercial sector/Industry
Name [1] 314182 0
Grand Theravac Life Sciences (Nanjing) Co., Ltd
Country [1] 314182 0
China
Primary sponsor type
Commercial sector/Industry
Name
Bestudy Australia Pty Ltd
Address
81-83 Campbell Street, Surry Hills, NSW 2010
Country
Australia
Secondary sponsor category [1] 316485 0
None
Name [1] 316485 0
Address [1] 316485 0
Country [1] 316485 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 313310 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 313310 0
Commercial Road, Melbourne 3004 VIC
Ethics committee country [1] 313310 0
Australia
Date submitted for ethics approval [1] 313310 0
27/07/2023
Approval date [1] 313310 0
31/07/2023
Ethics approval number [1] 313310 0
399/23 (HREC/100,081-Alfred-2023)

Summary
Brief summary
This project is evaluating the safety, tolerability (if any side effects occur), and immunogenicity (the ability of a molecule or substance to provoke an immune response) of two vaccinations with the study drug TVAX-006, a vaccine which is being developed with the aim to help prevent shingles. To evaluate the study drug, it will be tested in different groups who will receive different comparators.
Grand Theravac Life Sciences (Nanjing) Co., Ltd is developing the study vaccine, a recombinant zoster vaccine, as a potential new way to prevent shingles for adults aged between 30-70 years.
These long-term complications are the primary reason why vaccination is needed. Vaccination protects individuals from herpes zoster and postherpetic neuralgia and reduces associated medical and psychosocial outcomes and costs for the patient. The current treatments available once someone has herpes zoster and postherpetic neuralgia have limited success, so it is much better to prevent it from occurring at all. This makes vaccination a particularly important strategy for Australians to prevent this debilitating disease, especially in the elderly.
Trial website
Trial related presentations / publications
Public notes
One of the exclusion criteria, "15) Positive test for a nasopharyngeal swab for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [polymerase chain reaction (PCR)] before each vaccination." is moved in public notes as instructed.

Contacts
Principal investigator
Name 127690 0
Dr Kristi Mclendon
Address 127690 0
Level 5 Clive Berghofer Cancer Centre Research Centre, 300 Herston Road, Herston, QLD 4006
Country 127690 0
Australia
Phone 127690 0
+61 7 38453620
Fax 127690 0
Email 127690 0
[email protected]
Contact person for public queries
Name 127691 0
Kristi Mclendon
Address 127691 0
Level 5 Clive Berghofer Cancer Centre Research Centre, 300 Herston Road, Herston, QLD 4006
Country 127691 0
Australia
Phone 127691 0
+61 7 38453620
Fax 127691 0
Email 127691 0
[email protected]
Contact person for scientific queries
Name 127692 0
Kristi Mclendon
Address 127692 0
Level 5 Clive Berghofer Cancer Centre Research Centre, 300 Herston Road, Herston, QLD 4006
Country 127692 0
Australia
Phone 127692 0
+61 7 38453620
Fax 127692 0
Email 127692 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?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
19947Study protocol  [email protected]
19948Ethical approval  [email protected] 386158-(Uploaded-07-08-2023-21-52-48)-Study-related document.pdf



Results publications and other study-related documents

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