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Trial registered on ANZCTR


Registration number
ACTRN12621001009808
Ethics application status
Approved
Date submitted
15/07/2021
Date registered
2/08/2021
Date last updated
2/08/2021
Date data sharing statement initially provided
2/08/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
To Evaluate the Safety, Tolerability, and Immunogenicity of a PIKA-Adjuvanted Recombinant SARS-CoV-2 Spike (S) Protein Subunit Vaccine in Healthy Individuals
Scientific title
A Phase I, Open-label, Dose-Escalation, Single Site study to Evaluate the Safety, Tolerability, and Immunogenicity of a PIKA-Adjuvanted Recombinant SARS-CoV-2 Spike (S) Protein Subunit Vaccine in Healthy Individuals Aged 18-65 Years Old.
Secondary ID [1] 304718 0
YS-009
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
COVID 19 or SARS-CoV-2 Infection 322736 0
Condition category
Condition code
Respiratory 320328 320328 0 0
Other respiratory disorders / diseases
Infection 320474 320474 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a Phase I, open label, dose-escalation study of three dose levels of the SARS-CoV-2 spike antigen administered intramuscularly (IM) in combination with a fixed dosage of PIKA adjuvant vaccine to evaluate the safety, tolerability, and immunogenicity of PIKA COVID-19 vaccine candidate in healthy individuals aged 18-65 years. The study will be conducted in New Zealand at the New Zealand Clinical Research site located in the city of Christchurch.
There will be 3 dose groups, 1 to 3 with escalating antigen dose with PIKA adjuvant in sequential cohorts. A total of 45 subjects will be enrolled in this study. Subjects in Group 1-3 will receive two doses of PIKA COVID-19 vaccine via IM administration on Days 1 and 8.
The medical monitor and principal investigator will review the safety experience of all subjects enrolled in Group 1 through Study Day 8.
Fifteen eligible subjects in each dose group will receive the study vaccine on Study Days 1 and 8 via intramuscular injection in alternative deltoid muscles. Subjects will be sequentially assigned to a dose group based on the timing of completion of screening. Enrollment of each dose cohort will start with 3 sentinel subjects, at least one male and one female. The remaining subjects will be enrolled at least 48 hours later after the 3 sentinel subjects complete the first dose administration with no safety concerns as assessed by the Principal Investigator. The Medical Monitor and Principal Investigator will review the safety data of all subjects enrolled in Group 1 through Study Day 8. If no pausing rules have been met, Group 2 will be enrolled following the enrollment practice in Group 1. Accordingly, Group 3 can be enrolled when no pausing rules are met after all subjects in Group 2 completed Day 8 visit, as assessed by the Principal Investigator and local Medical Monitor. The enrollment of Group 3 will also follow the same enrollment practice as Groups 1 and 2. The duration of the entire study is anticipated to be 8 months from the start of screening to last subject visit. The duration of each individual subject is approximately 7 months from the consent to last visit
Dosage Form: Liquid
Composition: vaccine will be formulated pending on the dose cohort. Each vaccine will have varying amount S protein.
• 5 ug S protein/1mg PIKA
• 10 ug S protein /1mg PIKA
• 20 ug S protein /1mg PIKA

Route: Intramuscular injection into the deltoid muscle, the first dose to right arm and second dose on left arm.
Intervention code [1] 321096 0
Treatment: Drugs
Comparator / control treatment

No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 328175 0
To assess the safety and tolerability of the PIKA COVID-19 vaccine. Safety will be assessed by monitoring the solicited adverse events (AEs) for example Injection site reactions (pain, swelling, and erythema), fever, fatigue, nausea, headache and myalgia. Solicited adverse events will be recorded by diary card.
Timepoint [1] 328175 0
Solicited Adverse Events will be recorded on Day 1, Day 8, Day 15 post dose and during early termination if it is terminated before D15.
Primary outcome [2] 328176 0
Safety assessment will be done by monitoring unsolicited adverse events (AEs). Serious adverse events (SAEs), including suspected and unexpected serious reaction (SUSAR), adverse events of special interest (AESIs), and medically attended adverse events (MAAEs) will be recorded for the entire duration of the study.
Unsolicited AEs will be recorded for 7 days and 28 days, respectively, following each vaccine. These will be recorded by the participant in the participant diary and reviewed when the participant attends their visits at the site.
Timepoint [2] 328176 0
Unsolicited adverse events (AEs) will be recorded on Day 1, Day 8, Day 15, Day 36 post dose and at early termination if it is terminated before D36
Primary outcome [3] 328177 0
Safety will be assessed via clinical laboratory tests including hematology, biochemistry, coagulation
Timepoint [3] 328177 0
Blood samples will be collected at screening visit, Day 8, Day 15 post dose and at early termination. Should the participant withdraw prior to their Day 15 visit, they will come in for an additional Early Termination visit which includes the collection of samples for haematology, chemistry, coagulation, urinalysis, Neutralizing antibodies, Serum IgG and cellular immunity. Should they withdraw after their Day 15 visit, they will come in for an additional Early Termination visit which will include sample collection for Neutralizing antibodies, Serum IgG and cellular immunity.
Secondary outcome [1] 397942 0
To evaluate the serum neutralizing antibody response to the PIKA COVID-19 vaccine by
- Geometric mean titer (GMT) of neutralizing antibody against wild type SARS-CoV-2 and pseudotype or wildtype variants of concerns at baseline and pre-defined post-vaccination time points.
Timepoint [1] 397942 0
Neutralizing antibody test will be conducted by collecting blood samples at Day 1, Day 15, Day 36, Day 184 post dose and at early termination.
Should the participant withdraw prior to their Day 15 or after their Day 15 visit, they will come in for an additional Early Termination visit which will include the collection of a sample for Neutralizing antibody test.
Secondary outcome [2] 397943 0
To evaluate the cellular immune response to PIKA COVID-19 vaccine via frequency of CD4+ and CD8+ T cells expressing cytokines by intracellular staining (ICS) using Spike protein overlapping peptide pool.
Timepoint [2] 397943 0
Cellular immunity test will be conducted at Day 1, Day 15, Day 36, Day 184 post dose and at early termination.
Should the participant withdraw prior to their Day 15 or after their Day 15 visit, they will come in for an additional Early Termination visit which will include the collection of a sample for Cellular immunity testing.
Secondary outcome [3] 398110 0
Safety assessment will be done via urinalysis
Timepoint [3] 398110 0
Urine samples will be collected at screening visit, Day 8, Day 15 post dose and at early termination.
Should the participant withdraw prior to their Day 15 visit, they will come in for an additional Early Termination visit which includes the collection of a urine sample.
Secondary outcome [4] 398688 0
To evaluate the serum neutralizing antibody response to the PIKA COVID-19 vaccine by
- GMT of serum IgG against SARS-CoV-2 by ELISA
Timepoint [4] 398688 0
Serum IgG test will be conducted by collecting blood samples at Day 1, Day 15, Day 36, Day 184 post dose and at early termination.
Should the participant withdraw prior to their Day 15 or after their Day 15 visit, they will come in for an additional Early Termination visit which will include the collection of a sample for serum IgG testing.


Eligibility
Key inclusion criteria
1. Is age greater than equal to 18 and less than equal to 65 years on Study Day 1
2. Male and female healthy volunteers:
3. Judged by the investigator to be healthy on the basis of medical history, physical examination, vital signs, and no significant ECG abnormalities performed at screening
4. Able to provide informed consent form
5. Able and willing to comply with all study procedures over follow-up period of approximately 6 months
6. Body mass index of 18-32kg/square meter, inclusive, at screening
7. For female subjects with childbearing potential: must agree to avoid pregnancy from 21 days prior to study Day 1 until at least 90 days after last study vaccination. Women physically capable of pregnancy (not sterilized and still menstruating or within 1 year of the last menses if menopausal) in sexual relationships with men must use an acceptable method of avoiding pregnancy during this period. Acceptable methods of avoiding pregnancy include a sterile sexual partner, hormonal contraceptives (oral, injection, transdermal patch, or implant), vaginal ring, intrauterine device (IUD), or the combination of a condom or diaphragm.
8. Men must be willing to refrain from sperm donation, starting after screening until 90 days after receiving the last study vaccination. Male and female subjects must use a barrier method of contraception, from 21 days prior to study Day 1 until at least 90 days after last study vaccination. Barrier methods of contraception include:
• Male condoms
• Female condoms
• Female diaphragm (‘cap’)

Minimum age
18 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. History of COVID-19
2. Received partial or complete course of any type of COVID-19 vaccine.
3. History of close contact with a person infected or suspected of COVID-19 within 6 months prior to screening.
4. Positive test for SARS-CoV-2 infection, including but not limited to RT-PCR at screening
5. Positive rapid serological test (IgM or IgG against SARS-CoV-2) at screening or prior to first vaccination if available
6. Pregnant or breastfeeding or intending to become pregnant or father children within the projected duration of the trial
7. Currently working in an occupation with a high risk of exposure to SARS-CoV-2 (eg. Healthcare worker, emergency response personnel having direct interactions with or providing direct care to patients)
8. History of infection of Middle East Respiratory Syndrome (MERS), or Severe Acute Respiratory Syndrome (SARS)
9. Positive serology test results for hepatitis C virus antibody, HIV antibody, and/or hepatitis B virus surface antigen at Screening
10. Currently taking marketed, investigational, off-label product for the prevention of MERS, SARS, or COVID-19
11. Is currently participating in or has participated in a study with an investigational product within 30 days preceding Day 1
12. Fever (tympanic temperature greater than 37.5 degree C), dry cough, fatigue, nasal obstruction, runny nose, sore throat, myalgia, diarrhea, shortness of breath or dyspnea within 14 days before administration
13. Subjects with abnormal indicators, such as blood biochemistry, blood routine and urine routine deemed clinically significant by the investigator, or the value is beyond grade 1 per toxicity grading scale
14. History of severe allergic reactions (such as acute anaphylaxis, urticaria, skin eczema, dyspnea, angioneurotic edema or abdominal pain) or allergy to known composition of PIKA COVID-19 vaccine
15. History of convulsion, epilepsy, encephalopathy or severe mental illness
16. Diagnosed with congenital malformations or developmental disorders, genetic defects, severe malnutrition
17. Diagnosed with severe liver and kidney diseases, uncontrollable hypertension (systolic pressure greater than 140 mmHg, diastolic pressure greater than 90 mmHg), diabetic complications, malignant tumors, acute viral or bacterial infections or acute onset of chronic disease
18. Diagnosed with congenital or acquired immune deficiency, HIV infection, lymphoma, leukemia or other autoimmune diseases
19. History of coagulation dysfunction (e.g. Coagulation factor deficiency, coagulation disease)
20. Vaccinated with live attenuated vaccine within 1 month, or other vaccine within 14 days before vaccination
21. Receiving immunotherapy or inhibitor therapy within 3 months (consistently oral or infusion for more than 14 days)
22. Received systemic immunosuppressants within 4 months prior to vaccination, or anticipating the need for immunosuppressant at any time during participation in the study. Topical or inhaled treatment is allowed if not used within 14 days prior to vaccination.
23. Receiving blood products within 3 months before administration
24. History of alcohol or drug abuse within 3 years before first vaccination
25. Has donated 450ml or greater of blood within 28 days prior to vaccination
26. History of anaphylaxis or angioedema including but not limited to history of anaphylaxis after any vaccine.
27. Any condition that, in the opinion of the investigator, would pose a health risk to the subject if enrolled or could interfere with evaluation of the study vaccine or has interpretation of study results (including neurologic or psychiatric conditions deemed likely to impair the quality of safety reporting)

Study design
Purpose of the study
Treatment
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)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
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 outside Australia
Country [1] 23967 0
New Zealand
State/province [1] 23967 0
Auckland

Funding & Sponsors
Funding source category [1] 309088 0
Commercial sector/Industry
Name [1] 309088 0
Yisheng Biopharma (Singapore) Pte Ltd
Address [1] 309088 0
20 Maxwell Road
Maxwell house
#07-15
Singapore 069113
Country [1] 309088 0
Singapore
Primary sponsor type
Commercial sector/Industry
Name
Yisheng Biopharma (Singapore) Pte Ltd
Address
20 Maxwell Road
Maxwell house
#07-15
Singapore 069113
Country
Singapore
Secondary sponsor category [1] 310036 0
None
Name [1] 310036 0
Address [1] 310036 0
Country [1] 310036 0
Other collaborator category [1] 281908 0
Commercial sector/Industry
Name [1] 281908 0
Novotech (Australia) Pty Limited
Address [1] 281908 0
Novotech (Australia) Pty Limited
Level 3, 235 Pyrmont Street Sydney, NSW Australia - 2009
Country [1] 281908 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308962 0
Northern Health and Disability Ethics Committee
Ethics committee address [1] 308962 0
Committee B, Ministry of Health, Wellington 6140, PO Box 5013, New Zealand
Ethics committee country [1] 308962 0
New Zealand
Date submitted for ethics approval [1] 308962 0
13/07/2021
Approval date [1] 308962 0
20/07/2021
Ethics approval number [1] 308962 0

Summary
Brief summary
This is the first-in-human study of PIKA-adjuvanted PIKA covid-19 vaccine.
This is a Phase I, open label dose-escalation study of three dose levels of the SARS-CoV-2 spike antigen administered intramuscularly (IM) in combination with a fixed dosage of PIKA adjuvant vaccine to evaluate the safety, tolerability, and immunogenicity of PIKA COVID-19 vaccine candidate in healthy individuals aged 18-65 years.
There will be 3 dose groups, 1 to 3 with escalating antigen dose with PIKA adjuvant in sequential cohorts. A total of 45 subjects will be enrolled in this study. Subjects in Group 1-3 will receive two doses of PIKA COVID-19 vaccine via IM administration on Days 1 and 8.
Solicited and unsolicited adverse events (AEs) will be recorded for 7 days and 28 days, respectively, following each study injection. Serious adverse events (SAEs), including suspected and unexpected serious reaction (SUSAR), adverse events of special interest (AESIs), and medically attended adverse events (MAAEs) will be recorded for the entire duration of the study.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 112490 0
Dr Chris Wynne
Address 112490 0
New Zealand Clinical Research, Christchurch unit, Level 4/264 Antigua Street, Christchurch Central City, Christchurch, New Zealand, 8011
Country 112490 0
New Zealand
Phone 112490 0
+6433729477
Fax 112490 0
Email 112490 0
chris@ccst.co.nz
Contact person for public queries
Name 112491 0
Dr Chris Wynne
Address 112491 0
New Zealand Clinical Research, Christchurch unit, Level 4/264 Antigua Street, Christchurch Central City, Christchurch, New Zealand, 8011
Country 112491 0
New Zealand
Phone 112491 0
+6433729477
Fax 112491 0
Email 112491 0
chris@ccst.co.nz
Contact person for scientific queries
Name 112492 0
Dr Chris Wynne
Address 112492 0
New Zealand Clinical Research, Christchurch unit, Level 4/264 Antigua Street, Christchurch Central City, Christchurch, New Zealand, 8011
Country 112492 0
New Zealand
Phone 112492 0
+6433729477
Fax 112492 0
Email 112492 0
chris@ccst.co.nz

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 other documents available
Summary results
No Results