COVID-19 Disease, SARS Pneumonia, Pneumonia, Viral, COVID-19 Vaccine
Conditions
Keywords
COVID-19, COVIVAC, COVID-19 disease, SARS-CoV-2, COVID-19 vaccine
Brief summary
This prospective, single-center, randomized, placebo-controlled, observer-blind Phase 1/2 study includes two separate parts. Part 1 is a first-in-human, Phase 1 study designed to evaluate the safety, tolerability and immunogenicity of the COVIVAC vaccine at three different dose levels (1, 3, and 10 µg) without adjuvant, and at one dose level (1 µg) with the adjuvant CpG 1018, in a total of 120 subjects aged 18-59 years. (Part 2 will be registered in a separate record)
Detailed description
This prospective, single-center, randomized, placebo-controlled, observer-blind Phase 1/2 study includes two separate parts. Part 1 is a first-in-human, Phase 1 study designed to evaluate the safety, tolerability and immunogenicity of the COVIVAC vaccine at three different dose levels (1, 3, and 10 µg) without adjuvant, and at one dose level (1 µg) with the adjuvant CpG 1018, in a total of 120 subjects aged 18-59 years. An interim analysis of Phase 1 data conducted after the last subject last visit for V6 (D57) will serve as the basis for decisions about down selection and advancing to Part 2 of the study (Phase 2). Down selection and advancement to Part 2 (Phase 2) will be based on the following parameters: * Post-dose 2 immunogenicity results at the aggregate treatment level o A threshold immune response at Visit 5 (D43) will be required: the observed seroresponse rate in a treatment group (defined as the percentage of subjects with at least a 4-fold rise from baseline in 80% neutralizing antibody titers) will need to be ≥52% at the LL of the 95% CI for that treatment (vaccine formulation) to be considered for advancement to Phase 2. * Post-dose 1 and post dose 2 safety results including all solicited and unsolicited adverse events, serious adverse events, and clinical laboratory results. The following process will be followed for the decision about down selection and advancing to Part 2 (Phase 2): * The DSMB will review the unblinded safety data and provide a recommendation to the Sponsor on whether the safety profile is acceptable for advancing a formulation to Phase 2. * The Sponsor will review the DSMB recommendation in conjunction with the immunogenicity data and select two formulations to advance to Phase 2. o If multiple formulations achieve the threshold immune response (as well as have an adequate safety and tolerability profile per the DSMB), the Sponsor will select two formulations to advance to Phase 2 based on consideration of such factors as the relative functional immunogenicity of these formulations, opportunity for dose sparing, and opportunity to limit cost and possible supply constraints associated with use of the CpG adjuvant. * The selection and recommendation to advance to Phase 2 along with the interim report will be jointly reviewed by NIHE's IRB and MoH prior to Phase 2 enrollment.
Interventions
BIOLOGICALCOVIVAC
COVIVAC vaccine, manufactured by IVAC with or without adjuvant CpG1018 for prevention of COVID-19
BIOLOGICALPhosphate-buffered saline
Phosphate buffer solution (pH 7.2), manufactured by IVAC
Sponsors
National Institute of Hygiene and Epidemiology, Vietnam
Hanoi Medical University
Institute of Vaccines and Medical Biologicals, Vietnam
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
In Phase 1 is dose escalation design, eligible participants will be randomized to received study vaccine or placebo from low dose to higher dose and later to the formulation with CpG adjuvant.
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
Phase 1 Only: 1. Adult 18 through 59 years of age inclusive at the time of randomization. 2. Healthy, as defined by absence of clinically significant medical condition, either acute or chronic, as determined by medical history, physical examination, screening laboratory test results, and clinical assessment of the investigator. 3. Has provided written informed consent prior to performance of any study-specific procedure. 4. Has a body mass index (BMI) of 17 to 40 kg/m2, inclusive, at screening. 5. Resides in study site area and is able and willing to adhere to all protocol visits and procedures. 6. If a woman is of childbearing potential, must not be breastfeeding or be pregnant (based on a negative urine pregnancy test at screening and during the 24 hours prior to receipt of the first dose of IP), must plan to avoid pregnancy for at least 28 days after the last dose of IP, and be willing to use an adequate method of contraception consistently and have a repeated pregnancy test prior to the second (last) dose of IP.
Exclusion criteria
1. Use of any investigational medicinal product within 90 days prior to randomization or planned use of such a product during the period of study participation. 2. History of administration of any non-study vaccine within 28 days prior to administration of study vaccine or planned vaccination within 3 months after enrolment. Note: receipt of any COVID-19 vaccine that is licensed or granted Emergency Use Authorization in Vietnam during the course of study participation is not exclusionary if administered after Visit 5. 3. Previous receipt of investigational vaccine for SARS or MERS, or any investigational or licensed vaccine that may have an impact on interpretation of the trial results 4. History of hypersensitivity reaction to any prior vaccination or known hypersensitivity to any component of the study vaccine 5. History of egg or chicken allergy 6. History of angioedema 7. History of anaphylaxis 8. Acute illness (moderate or severe) and/or fever (body temperature measured orally ≥38°C) 9. Any abnormal vital sign deemed clinically relevant by the PI 10. Abnormality in screening laboratory test deemed exclusionary by the PI in consultation with the Sponsor 11. A positive serologic test for hepatitis B (HBsAg) or hepatitis C (HCV Ab) 12. History of confirmed HIV 13. History of laboratory-confirmed COVID-19 14. History of malignancy, excluding non-melanoma skin and cervical carcinoma in situ 15. Any confirmed or suspected immunosuppressive or immunodeficient state 16. Administration of immunoglobulin or any blood product within 90 days prior to first study injection or planned administration during the study period. 17. Administration of any long-acting immune-modifying drugs (e.g., infliximab or rituximab) or the chronic administration (defined as more than 14 days) of immunosuppressants within six months prior to first study injection, or planned administration during the study period (includes systemic corticosteroids at doses equivalent to ≥ 0.5 mg/kg/day of prednisone; the use of topical steroids including inhaled and intranasal steroids is permitted). 18. History of known disturbance of coagulation or blood disorder that could cause anemia or excess bleeding. (e.g, thalassemia, coagulation factor deficiencies). 19. Recent history (within the past year) or signs of alcohol or substance abuse. 20. Any medical, psychiatric or behavior condition that in the opinion of the PI may interfere with the study objectives, pose a risk to the subject, or prevent the subject from completing the study follow-up. 21. Employee of any person employed by the Sponsor, the contract research organization (CRO), the PI, study site personnel, or site.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Event of Special Interest | Throughout the Study Period (until Day 197) | Number of participants with adverse events of special interest (AESI) , including AESI relevant to COVID-19, and potential immune-mediated medical conditions (PIMMC) |
| Solicited Adverse Events | During the first 7 days after each vaccination | Percentage of participants with solicited local and systemic adverse events (AEs) |
| Clinical Safety Tests | At 7 days post each vaccination | Percentage of participants with clinically significant hematological and biochemical abnormalities |
| Unsolicited Adverse Events | During the first 28 days after each vaccination | Number of participants with any unsolicited adverse event |
| Serious Adverse Event | Throughout the Study Period (until Day 197) | Number of participants with serious adverse events (SAEs) |
| Medical Attended Adverse Events | Throughout the Study Period (until Day 197) | Number of participants with medically-attended AEs (MAAEs) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| GMT of 50% Neutralizing Antibody (NT50) | GMT of NT50 at 28 days after first vaccination, at 14 days and 6 months after the second vaccination | 50% neutralizing antibody (NT50) geometric mean titer (GMT) against SARS-CoV-2 pseudovirus |
| Geometric Mean Fold Rise (GMFR) | GMFR at 28 days after first vaccination, at 14 days and 6 months after the second vaccination | Geometric mean fold rise (GMFR) (from baseline) in NT50 against SARS-CoV-2 pseudovirus |
| Seroresponse in NT50 | Seroresponse at 28 days after first vaccination, at 14 days and 6 months after the second vaccination | Percentage of subjects with NT50 seroresponse against SARS-CoV-2 pseudovirus as defined by (1) a ≥ 4-fold increase from baseline, and (2) a ≥ 10-fold increase from baseline |
| Anti-S IgG GMC | GMC of Anti-S IgG at 28 days after the first vaccination, at 14 days and 6 months after the second vaccination | Immunogenicity outcome measurement |
| GMFR in Anti-S IgG GMC | GMFR at 28 days after the first vaccination, 14 days and 6 months after the second vaccination | GMFR (from baseline) in anti-S IgG GMC |
| Seroresponse in Anti-S IgG Concentration | Seroresponse at 28 days after the first vaccination, 14 days and 6 months after the second vaccination | Percentage of subjects with seroresponses in anti-S IgG titer as defined by (1) a ≥ 4-fold increase from baseline, and (2) a ≥ 10-fold increase from baseline |
Countries
Vietnam
Participant flow
Recruitment details
The screening and enrollment were conducted from 10 Mar 2021 to 17 April 2021 at the clinical trial center of Hanoi Medical University. Total 224 subjects were screened, and 120 subjects were randomized to 5 treatment arms (25 for each of 4 study vaccine doses/formulation and 20 for placebo cohort).
Pre-assignment details
This is a first-in-human with dose escalation. There are 4 groups, each group (25 subjects for each vaccine dose/formulation + 5 subject of placebo cohort) will be divided into two sequential subgroups, a sentinel subgroup (n=6) and a larger subgroup (n=24) that includes the remaining subjects to be evaluated at that dose level (or for that formulation in the case of the one adjuvanted treatment group).
Participants by arm
| Arm | Count |
|---|---|
| COVIVAC 1mcg 1mcg IVAC COVIVAC vaccine for intramuscular injection administered as two doses (0.5mL each) 28 days apart.
COVIVAC: COVIVAC vaccine, manufactured by IVAC with or without adjuvant CpG1018 for prevention of COVID-19 | 25 |
| COVIVAC 3mcg 3mcg IVAC COVIVAC vaccine for intramuscular injection administered as two doses (0.5mL each) 28 days apart.
COVIVAC: COVIVAC vaccine, manufactured by IVAC with or without adjuvant CpG1018 for prevention of COVID-19 | 25 |
| COVIVAC 10mcg 10mcg IVAC COVIVAC vaccine for intramuscular injection administered as two doses (0.5mL each) 28 days apart.
COVIVAC: COVIVAC vaccine, manufactured by IVAC with or without adjuvant CpG1018 for prevention of COVID-19 | 25 |
| COVIVAC 1mcg + CpG1018 1.5mg 1mcg + CpG1018 IVAC COVIVAC vaccine for intramuscular injection administered as two doses (0.5mL each) 28 days apart.
COVIVAC: COVIVAC vaccine, manufactured by IVAC with or without adjuvant CpG1018 for prevention of COVID-19 | 25 |
| Placebo Phosphate buffered saline (pH 7.2) for intramuscular injection administered as two doses (0.5mL each) 28 days apart.
Phosphate-buffered saline: Phosphate buffer solution (pH 7.2), manufactured by IVAC | 20 |
| Total | 120 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | 4 subject was missing value at visit 7 (Day 197) due to migrated/moved from the study area. | 2 | 1 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | COVIVAC 1mcg | COVIVAC 3mcg | COVIVAC 10mcg | COVIVAC 1mcg + CpG1018 1.5mg | Placebo | Total |
|---|---|---|---|---|---|---|
| Age, Continuous Age | 34.4 Years STANDARD_DEVIATION 11.9 | 36.7 Years STANDARD_DEVIATION 12.1 | 34.3 Years STANDARD_DEVIATION 10.6 | 35.1 Years STANDARD_DEVIATION 11.9 | 32.4 Years STANDARD_DEVIATION 11.5 | 34.7 Years STANDARD_DEVIATION 11.5 |
| BMI | 22.1 kg/m^2 STANDARD_DEVIATION 2.8 | 22.8 kg/m^2 STANDARD_DEVIATION 2.1 | 22.9 kg/m^2 STANDARD_DEVIATION 2.5 | 22.3 kg/m^2 STANDARD_DEVIATION 2.4 | 22.7 kg/m^2 STANDARD_DEVIATION 2.7 | 22.6 kg/m^2 STANDARD_DEVIATION 2.5 |
| Race/Ethnicity, Customized Asian | 25 participants | 25 participants | 25 participants | 25 participants | 20 participants | 120 participants |
| Race/Ethnicity, Customized Kinh (Ethnicity) | 25 participants | 23 participants | 25 participants | 25 participants | 19 participants | 117 participants |
| Race/Ethnicity, Customized Other (Ethnicity) | 00 participants | 2 participants | 0 participants | 0 participants | 1 participants | 3 participants |
| Region of Enrollment Vietnam | 25 participants | 25 participants | 25 participants | 25 participants | 20 participants | 120 participants |
| Sex: Female, Male Female | 12 Participants | 11 Participants | 12 Participants | 13 Participants | 10 Participants | 58 Participants |
| Sex: Female, Male Male | 13 Participants | 14 Participants | 13 Participants | 12 Participants | 10 Participants | 62 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 25 | 0 / 25 | 0 / 25 | 0 / 25 | 0 / 20 |
| other Total, other adverse events | 4 / 25 | 3 / 25 | 0 / 25 | 2 / 25 | 0 / 20 |
| serious Total, serious adverse events | 0 / 25 | 0 / 25 | 0 / 25 | 1 / 25 | 1 / 20 |
Outcome results
Primary
Adverse Event of Special Interest
Number of participants with adverse events of special interest (AESI) , including AESI relevant to COVID-19, and potential immune-mediated medical conditions (PIMMC)
Time frame: Throughout the Study Period (until Day 197)
Population: There are 116 subject attended the follow-up visit day 197 (23 subjects in 1mcg arm, 24 subjects in 3mcg arm, 25 subjects in 10mcg arm, 24 subjects in 1mcg + CpG arm, and 20 subjects in placebo arm).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| COVIVAC 1 mcg | Adverse Event of Special Interest | 0 Participants |
| COVIVAC 3 mcg | Adverse Event of Special Interest | 0 Participants |
| COVIVAC 10 mcg | Adverse Event of Special Interest | 0 Participants |
| COVIVAC 1mcg + CpG | Adverse Event of Special Interest | 0 Participants |
| Placebo | Adverse Event of Special Interest | 0 Participants |
Primary
Clinical Safety Tests
Percentage of participants with clinically significant hematological and biochemical abnormalities
Time frame: At 7 days post each vaccination
Population: All participants receiving at least one dose of study vaccine/placebo will be included in the safety analysis population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| COVIVAC 1 mcg | Clinical Safety Tests | 0 percent of participants |
| COVIVAC 3 mcg | Clinical Safety Tests | 0 percent of participants |
| COVIVAC 10 mcg | Clinical Safety Tests | 0 percent of participants |
| COVIVAC 1mcg + CpG | Clinical Safety Tests | 0 percent of participants |
| Placebo | Clinical Safety Tests | 0 percent of participants |
Primary
Medical Attended Adverse Events
Number of participants with medically-attended AEs (MAAEs)
Time frame: Throughout the Study Period (until Day 197)
Population: There are 116 subject attended the follow-up visit day 197 (23 subjects in 1mcg arm, 24 subjects in 3mcg arm, 25 subjects in 10mcg arm, 24 subjects in 1mcg + CpG arm, and 20 subjects in placebo arm).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| COVIVAC 1 mcg | Medical Attended Adverse Events | 3 Participants |
| COVIVAC 3 mcg | Medical Attended Adverse Events | 3 Participants |
| COVIVAC 10 mcg | Medical Attended Adverse Events | 2 Participants |
| COVIVAC 1mcg + CpG | Medical Attended Adverse Events | 2 Participants |
| Placebo | Medical Attended Adverse Events | 0 Participants |
Primary
Serious Adverse Event
Number of participants with serious adverse events (SAEs)
Time frame: Throughout the Study Period (until Day 197)
Population: There are 116 subject attended the follow-up visit day 197 (23 subjects in 1mcg arm, 24 subjects in 3mcg arm, 25 subjects in 10mcg arm, 24 subjects in 1mcg + CpG arm, and 20 subjects in placebo arm)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| COVIVAC 1 mcg | Serious Adverse Event | 0.0 percent of participants |
| COVIVAC 3 mcg | Serious Adverse Event | 0.0 percent of participants |
| COVIVAC 10 mcg | Serious Adverse Event | 0.0 percent of participants |
| COVIVAC 1mcg + CpG | Serious Adverse Event | 4.0 percent of participants |
| Placebo | Serious Adverse Event | 5.0 percent of participants |
Primary
Solicited Adverse Events
Percentage of participants with solicited local and systemic adverse events (AEs)
Time frame: During the first 7 days after each vaccination
Population: All participants receiving at least one dose of study vaccine/placebo will be included in the safety analysis population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| COVIVAC 1 mcg | Solicited Adverse Events | 88.0 percent of participants |
| COVIVAC 3 mcg | Solicited Adverse Events | 68.0 percent of participants |
| COVIVAC 10 mcg | Solicited Adverse Events | 88.0 percent of participants |
| COVIVAC 1mcg + CpG | Solicited Adverse Events | 80.0 percent of participants |
| Placebo | Solicited Adverse Events | 70.0 percent of participants |
Primary
Unsolicited Adverse Events
Number of participants with any unsolicited adverse event
Time frame: During the first 28 days after each vaccination
Population: All participants receiving at least one dose of study vaccine/placebo will be included in the safety analysis population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| COVIVAC 1 mcg | Unsolicited Adverse Events | 44.0 percent of participants |
| COVIVAC 3 mcg | Unsolicited Adverse Events | 32.0 percent of participants |
| COVIVAC 10 mcg | Unsolicited Adverse Events | 48.0 percent of participants |
| COVIVAC 1mcg + CpG | Unsolicited Adverse Events | 52.0 percent of participants |
| Placebo | Unsolicited Adverse Events | 45.0 percent of participants |
Secondary
Anti-S IgG GMC
Immunogenicity outcome measurement
Time frame: GMC of Anti-S IgG at 28 days after the first vaccination, at 14 days and 6 months after the second vaccination
Population: GMCs are analyzed from subjects with seronegative anti-S IgG at baseline. There are 5 subjects were sero-positive at baseline (anti-S IgG ≥50.3 ELU/mL), and 8 subjects were missed visit at visit 7 (Day 197).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| COVIVAC 1 mcg | Anti-S IgG GMC | GMC of Anti-S IgG at 28 days after first vaccination | 9.89 BAU/ml |
| COVIVAC 1 mcg | Anti-S IgG GMC | GMC of Anti-S IgG at 6 months after second vaccination | 242.54 BAU/ml |
| COVIVAC 1 mcg | Anti-S IgG GMC | GMC of Anti-S IgG at 14 days after second vaccination | 122.54 BAU/ml |
| COVIVAC 3 mcg | Anti-S IgG GMC | GMC of Anti-S IgG at 14 days after second vaccination | 173.38 BAU/ml |
| COVIVAC 3 mcg | Anti-S IgG GMC | GMC of Anti-S IgG at 28 days after first vaccination | 15.35 BAU/ml |
| COVIVAC 3 mcg | Anti-S IgG GMC | GMC of Anti-S IgG at 6 months after second vaccination | 469.36 BAU/ml |
| COVIVAC 10 mcg | Anti-S IgG GMC | GMC of Anti-S IgG at 14 days after second vaccination | 446.50 BAU/ml |
| COVIVAC 10 mcg | Anti-S IgG GMC | GMC of Anti-S IgG at 28 days after first vaccination | 29.33 BAU/ml |
| COVIVAC 10 mcg | Anti-S IgG GMC | GMC of Anti-S IgG at 6 months after second vaccination | 515.41 BAU/ml |
| COVIVAC 1mcg + CpG | Anti-S IgG GMC | GMC of Anti-S IgG at 28 days after first vaccination | 6.40 BAU/ml |
| COVIVAC 1mcg + CpG | Anti-S IgG GMC | GMC of Anti-S IgG at 6 months after second vaccination | 350.79 BAU/ml |
| COVIVAC 1mcg + CpG | Anti-S IgG GMC | GMC of Anti-S IgG at 14 days after second vaccination | 206.51 BAU/ml |
| Placebo | Anti-S IgG GMC | GMC of Anti-S IgG at 14 days after second vaccination | 3.15 BAU/ml |
| Placebo | Anti-S IgG GMC | GMC of Anti-S IgG at 28 days after first vaccination | 3.15 BAU/ml |
| Placebo | Anti-S IgG GMC | GMC of Anti-S IgG at 6 months after second vaccination | 85.98 BAU/ml |
Secondary
Geometric Mean Fold Rise (GMFR)
Geometric mean fold rise (GMFR) (from baseline) in NT50 against SARS-CoV-2 pseudovirus
Time frame: GMFR at 28 days after first vaccination, at 14 days and 6 months after the second vaccination
Population: There are 2 subjects (1 μg) were invalid result (IR) at visit 3 (Day 29), 8 subjects were missed visit at visit 7 (Day 197), and 1 subject (visit 7 (Day 197)) was not having a sufficient quantity (volume) of specimen to test (QNS- Quantity not sufficient).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| COVIVAC 1 mcg | Geometric Mean Fold Rise (GMFR) | GMFR at 28 after first vaccination | 2.06 fold rise |
| COVIVAC 1 mcg | Geometric Mean Fold Rise (GMFR) | GMFR at 6 months after second vaccination | 49.53 fold rise |
| COVIVAC 1 mcg | Geometric Mean Fold Rise (GMFR) | GMFR at 14 days after first vaccination | 22.50 fold rise |
| COVIVAC 3 mcg | Geometric Mean Fold Rise (GMFR) | GMFR at 14 days after first vaccination | 34.05 fold rise |
| COVIVAC 3 mcg | Geometric Mean Fold Rise (GMFR) | GMFR at 28 after first vaccination | 1.70 fold rise |
| COVIVAC 3 mcg | Geometric Mean Fold Rise (GMFR) | GMFR at 6 months after second vaccination | 121.40 fold rise |
| COVIVAC 10 mcg | Geometric Mean Fold Rise (GMFR) | GMFR at 14 days after first vaccination | 84.75 fold rise |
| COVIVAC 10 mcg | Geometric Mean Fold Rise (GMFR) | GMFR at 28 after first vaccination | 4.91 fold rise |
| COVIVAC 10 mcg | Geometric Mean Fold Rise (GMFR) | GMFR at 6 months after second vaccination | 103.27 fold rise |
| COVIVAC 1mcg + CpG | Geometric Mean Fold Rise (GMFR) | GMFR at 28 after first vaccination | 1.87 fold rise |
| COVIVAC 1mcg + CpG | Geometric Mean Fold Rise (GMFR) | GMFR at 6 months after second vaccination | 90.47 fold rise |
| COVIVAC 1mcg + CpG | Geometric Mean Fold Rise (GMFR) | GMFR at 14 days after first vaccination | 53.66 fold rise |
| Placebo | Geometric Mean Fold Rise (GMFR) | GMFR at 14 days after first vaccination | 1.00 fold rise |
| Placebo | Geometric Mean Fold Rise (GMFR) | GMFR at 28 after first vaccination | 1.00 fold rise |
| Placebo | Geometric Mean Fold Rise (GMFR) | GMFR at 6 months after second vaccination | 4.42 fold rise |
Secondary
GMFR in Anti-S IgG GMC
GMFR (from baseline) in anti-S IgG GMC
Time frame: GMFR at 28 days after the first vaccination, 14 days and 6 months after the second vaccination
Population: There are and 8 subjects were missed visit at visit 7 (Day 197).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| COVIVAC 1 mcg | GMFR in Anti-S IgG GMC | GMFR at 28 days after first vaccination | 3.00 fold rise |
| COVIVAC 1 mcg | GMFR in Anti-S IgG GMC | GMFR at 6 months after second vaccination | 103.13 fold rise |
| COVIVAC 1 mcg | GMFR in Anti-S IgG GMC | GMFR at 14 days after second vaccination | 34.65 fold rise |
| COVIVAC 3 mcg | GMFR in Anti-S IgG GMC | GMFR at 14 days after second vaccination | 55.02 fold rise |
| COVIVAC 3 mcg | GMFR in Anti-S IgG GMC | GMFR at 28 days after first vaccination | 4.87 fold rise |
| COVIVAC 3 mcg | GMFR in Anti-S IgG GMC | GMFR at 6 months after second vaccination | 148.95 fold rise |
| COVIVAC 10 mcg | GMFR in Anti-S IgG GMC | GMFR at 14 days after second vaccination | 124.11 fold rise |
| COVIVAC 10 mcg | GMFR in Anti-S IgG GMC | GMFR at 28 days after first vaccination | 9.14 fold rise |
| COVIVAC 10 mcg | GMFR in Anti-S IgG GMC | GMFR at 6 months after second vaccination | 147.60 fold rise |
| COVIVAC 1mcg + CpG | GMFR in Anti-S IgG GMC | GMFR at 28 days after first vaccination | 2.03 fold rise |
| COVIVAC 1mcg + CpG | GMFR in Anti-S IgG GMC | GMFR at 6 months after second vaccination | 111.33 fold rise |
| COVIVAC 1mcg + CpG | GMFR in Anti-S IgG GMC | GMFR at 14 days after second vaccination | 65.54 fold rise |
| Placebo | GMFR in Anti-S IgG GMC | GMFR at 14 days after second vaccination | 0.98 fold rise |
| Placebo | GMFR in Anti-S IgG GMC | GMFR at 28 days after first vaccination | 1.00 fold rise |
| Placebo | GMFR in Anti-S IgG GMC | GMFR at 6 months after second vaccination | 30.61 fold rise |
Secondary
GMT of 50% Neutralizing Antibody (NT50)
50% neutralizing antibody (NT50) geometric mean titer (GMT) against SARS-CoV-2 pseudovirus
Time frame: GMT of NT50 at 28 days after first vaccination, at 14 days and 6 months after the second vaccination
Population: NT50 GMTs are analyzed from subjects with seronegative anti-S IgG at baseline. There were 5 subjects with sero-positive at baseline (anti-S IgG ≥50.3 ELU/mL), 2 subjects (1 μg) with invalid result (IR) at visit 3 (Day 29), 8 subjects missed visit at visit 7 (Day 197), and 1 subject (visit 7 (Day 197)) was not having a sufficient quantity (volume) of specimen to test (QNS- Quantity not sufficient).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| COVIVAC 1 mcg | GMT of 50% Neutralizing Antibody (NT50) | GMT of NT50 at 28 days after first vaccination | 10.67 IU/ml |
| COVIVAC 1 mcg | GMT of 50% Neutralizing Antibody (NT50) | GMT of NT50 at 6 months after second vaccination | 230.72 IU/ml |
| COVIVAC 1 mcg | GMT of 50% Neutralizing Antibody (NT50) | GMT of NT50 at 14 days after second vaccination | 104.96 IU/ml |
| COVIVAC 3 mcg | GMT of 50% Neutralizing Antibody (NT50) | GMT of NT50 at 14 days after second vaccination | 170.24 IU/ml |
| COVIVAC 3 mcg | GMT of 50% Neutralizing Antibody (NT50) | GMT of NT50 at 28 days after first vaccination | 8.48 IU/ml |
| COVIVAC 3 mcg | GMT of 50% Neutralizing Antibody (NT50) | GMT of NT50 at 6 months after second vaccination | 607.00 IU/ml |
| COVIVAC 10 mcg | GMT of 50% Neutralizing Antibody (NT50) | GMT of NT50 at 14 days after second vaccination | 460.87 IU/ml |
| COVIVAC 10 mcg | GMT of 50% Neutralizing Antibody (NT50) | GMT of NT50 at 28 days after first vaccination | 23.50 IU/ml |
| COVIVAC 10 mcg | GMT of 50% Neutralizing Antibody (NT50) | GMT of NT50 at 6 months after second vaccination | 556.25 IU/ml |
| COVIVAC 1mcg + CpG | GMT of 50% Neutralizing Antibody (NT50) | GMT of NT50 at 28 days after first vaccination | 9.35 IU/ml |
| COVIVAC 1mcg + CpG | GMT of 50% Neutralizing Antibody (NT50) | GMT of NT50 at 6 months after second vaccination | 452.35 IU/ml |
| COVIVAC 1mcg + CpG | GMT of 50% Neutralizing Antibody (NT50) | GMT of NT50 at 14 days after second vaccination | 268.32 IU/ml |
| Placebo | GMT of 50% Neutralizing Antibody (NT50) | GMT of NT50 at 14 days after second vaccination | 5.00 IU/ml |
| Placebo | GMT of 50% Neutralizing Antibody (NT50) | GMT of NT50 at 28 days after first vaccination | 5.00 IU/ml |
| Placebo | GMT of 50% Neutralizing Antibody (NT50) | GMT of NT50 at 6 months after second vaccination | 20.27 IU/ml |
Secondary
Seroresponse in Anti-S IgG Concentration
Percentage of subjects with seroresponses in anti-S IgG titer as defined by (1) a ≥ 4-fold increase from baseline, and (2) a ≥ 10-fold increase from baseline
Time frame: Seroresponse at 28 days after the first vaccination, 14 days and 6 months after the second vaccination
Population: There are 8 subjects were missed visit at visit 7 (Day 197).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| COVIVAC 1 mcg | Seroresponse in Anti-S IgG Concentration | Seroresponse at 28 days after first vaccination | 44.2 percentage of participants |
| COVIVAC 1 mcg | Seroresponse in Anti-S IgG Concentration | Seroresponse at 6 months after second vaccination | 82.6 percentage of participants |
| COVIVAC 1 mcg | Seroresponse in Anti-S IgG Concentration | Seroresponse at 14 days after second vaccination | 82.5 percentage of participants |
| COVIVAC 3 mcg | Seroresponse in Anti-S IgG Concentration | Seroresponse at 14 days after second vaccination | 96.0 percentage of participants |
| COVIVAC 3 mcg | Seroresponse in Anti-S IgG Concentration | Seroresponse at 28 days after first vaccination | 44.0 percentage of participants |
| COVIVAC 3 mcg | Seroresponse in Anti-S IgG Concentration | Seroresponse at 6 months after second vaccination | 87.5 percentage of participants |
| COVIVAC 10 mcg | Seroresponse in Anti-S IgG Concentration | Seroresponse at 14 days after second vaccination | 100.0 percentage of participants |
| COVIVAC 10 mcg | Seroresponse in Anti-S IgG Concentration | Seroresponse at 28 days after first vaccination | 64.0 percentage of participants |
| COVIVAC 10 mcg | Seroresponse in Anti-S IgG Concentration | Seroresponse at 6 months after second vaccination | 100 percentage of participants |
| COVIVAC 1mcg + CpG | Seroresponse in Anti-S IgG Concentration | Seroresponse at 28 days after first vaccination | 84.0 percentage of participants |
| COVIVAC 1mcg + CpG | Seroresponse in Anti-S IgG Concentration | Seroresponse at 6 months after second vaccination | 90.9 percentage of participants |
| COVIVAC 1mcg + CpG | Seroresponse in Anti-S IgG Concentration | Seroresponse at 14 days after second vaccination | 100.0 percentage of participants |
| Placebo | Seroresponse in Anti-S IgG Concentration | Seroresponse at 14 days after second vaccination | 0.0 percentage of participants |
| Placebo | Seroresponse in Anti-S IgG Concentration | Seroresponse at 28 days after first vaccination | 0.0 percentage of participants |
| Placebo | Seroresponse in Anti-S IgG Concentration | Seroresponse at 6 months after second vaccination | 89.5 percentage of participants |
Secondary
Seroresponse in NT50
Percentage of subjects with NT50 seroresponse against SARS-CoV-2 pseudovirus as defined by (1) a ≥ 4-fold increase from baseline, and (2) a ≥ 10-fold increase from baseline
Time frame: Seroresponse at 28 days after first vaccination, at 14 days and 6 months after the second vaccination
Population: NT50 GMTs are analyzed from subjects with seronegative anti-S IgG at baseline. There were 2 subjects (1 μg) with invalid result (IR) at visit 3 (Day 29), 8 subjects missed visit at visit 7 (Day 197), and 1 subject (visit 7 (Day 197)) was not having a sufficient quantity (volume) of specimen to test (QNS- Quantity not sufficient).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| COVIVAC 1 mcg | Seroresponse in NT50 | Seroresponse at 28 days after first vaccination | 13.0 percentage of participants |
| COVIVAC 1 mcg | Seroresponse in NT50 | Seroresponse at 6 months after second vaccination | 68.2 percentage of participants |
| COVIVAC 1 mcg | Seroresponse in NT50 | Seroresponse at 14 days after second vaccination | 84.0 percentage of participants |
| COVIVAC 3 mcg | Seroresponse in NT50 | Seroresponse at 14 days after second vaccination | 96.0 percentage of participants |
| COVIVAC 3 mcg | Seroresponse in NT50 | Seroresponse at 28 days after first vaccination | 0.0 percentage of participants |
| COVIVAC 3 mcg | Seroresponse in NT50 | Seroresponse at 6 months after second vaccination | 87.5 percentage of participants |
| COVIVAC 10 mcg | Seroresponse in NT50 | Seroresponse at 14 days after second vaccination | 96.0 percentage of participants |
| COVIVAC 10 mcg | Seroresponse in NT50 | Seroresponse at 28 days after first vaccination | 40.0 percentage of participants |
| COVIVAC 10 mcg | Seroresponse in NT50 | Seroresponse at 6 months after second vaccination | 87.5 percentage of participants |
| COVIVAC 1mcg + CpG | Seroresponse in NT50 | Seroresponse at 28 days after first vaccination | 8.0 percentage of participants |
| COVIVAC 1mcg + CpG | Seroresponse in NT50 | Seroresponse at 6 months after second vaccination | 81.8 percentage of participants |
| COVIVAC 1mcg + CpG | Seroresponse in NT50 | Seroresponse at 14 days after second vaccination | 96.0 percentage of participants |
| Placebo | Seroresponse in NT50 | Seroresponse at 14 days after second vaccination | 0.0 percentage of participants |
| Placebo | Seroresponse in NT50 | Seroresponse at 28 days after first vaccination | 0.0 percentage of participants |
| Placebo | Seroresponse in NT50 | Seroresponse at 6 months after second vaccination | 26.3 percentage of participants |