Immunogenicity of a Single Dose of BIVALENT Pfizer/BNT Vaccine, Immunogenicity of a Single Dose of COMVIGEN Vaccine, Reactogenicity of a Single Dose of BIVALENT Pfizer/BNT Vaccine, Reactogenicity of a Single Dose of COMVIGEN Vaccine, Safety of a Single Dose of BIVALENT Pfizer/BNT Vaccine, Safety of a Single Dose of COMVIGEN Vaccine
Conditions
Keywords
Non-inferiority study, Open-label, Randomized Controlled Study, Immunogenicity of the booster dose, safety of booster dose, reactogenicity of booster dose, COMVIGEN (Bivalent, ChulaCov19 BNA159.2 vaccine), Pfizer bivalent vaccine (Comirnaty, BIVALENT), mRNA from the ancestral (original) strain, Omicron variant (BA.4/BA.5) of SARS-CoV-2
Brief summary
This study will assess the safety, reactogenicity and immunogenicity of a single dose of Comvigen (Bivalent, ChulaCov19 BNA159.2) vaccine or BIVALENT Pfizer/BNT vaccine as a booster among healthy males and non-pregnant females aged 18-64 years after receiving a previous booster dose of any approved mRNA COVID-19 vaccine for more than 3 months. The results of Combiven will be compared to BIVALENT Pfizer/BNT vaccine.
Detailed description
This is a phase II, non-inferiority, multicenter randomized open-label trial in which 450 healthy males and non-pregnant females, aged 18-64 years, will be recruited from multi-sites in Thailand. The randomization will be a 2:1 design to receive either Comvigen (Bivalent, ChulaCov19 BNA159.2) vaccine or BIVALENT Pfizer/BNT vaccine. This clinical trial is designed to assess the safety, reactogenicity and immunogenicity of a single dose of COMVIGEN at 50 ug, as a booster dose, given at 3 months and above after receipt of a previous booster dose of any approved mRNA COVID-19 vaccine. The estimated sample size would also allow a comparison between a booster dose, Comvigen (Bivalent, ChulaCov19 BNA159.2) vaccine at 50 ug to Comirnaty, BIVALENT of Pfizer/BNT Bivalent vaccine at 30 ug dose.
Interventions
BIOLOGICALComvigen (Bivalent, ChulaCov19 BNA159.2)
single dose of COMVIGEN at 50 ug, as a booster dose, given at 3 months and above after receipt of a previous booster dose of any approved mRNA COVID-19 vaccine
BIOLOGICALBIVALENT Pfizer/BNT vaccine
single dose of BIVALENT of Pfizer/BNT Bivalent vaccine at 30 ug, as a booster dose, given at 3 months and above after receipt of a previous booster dose of any approved mRNA COVID-19 vaccine
Sponsors
Chula Clinical Research Center (Chula CRC), Faculty of Medicine Chulalongkorn University, Bangkok, Thailand
HIV-NAT, Thai Red Cross - AIDS Research Centre
Chulalongkorn University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
Yes
Inclusion criteria
Participants who meet all the following criteria at Screening are eligible to participate in the study: 1. Must be a male or female aged 18 - 64 (inclusive) at the time of enrolment 2. Must have completed at least a primary course of 2 doses of any approved COVID-19 vaccine which the last dose have to be mRNA vaccine and completed the last doser 3 months or more 3. Must be able to communicate effectively with study personnel and considered reliable, willing, and cooperative in terms of compliance with the protocol requirements 4. Participants must sign the written informed consent form prior to undertaking any protocol-related procedures 5. SARS-CoV-2 rapid antigen test is negative at Day 1 (the day of receiving the study booster dose) 6. Does not intend to receive any other authorized/approved COVID-19 vaccine at the time of enrolment and up to 3 months of the study 7. Males must be surgically sterile (\>30 days since vasectomy with no viable sperm), practice true abstinence or, if engaged in sexual relations with a female of child-bearing potential, the participants and their partner must use an acceptable, highly effective, double-barrier contraceptive method\* from Screening and for a period of at least 60 days after vaccination 8. A female participant is eligible if she is not pregnant, or breastfeeding indicated by one of the following conditions: 1. With childbearing potential (WOCBP): she agrees to use an effective contraceptive method or abstinence from at least 4 weeks prior to the study intervention administration until at least 12 weeks after the study intervention administration, or 2. With non-childbearing potential. To be considered of non-childbearing potential, a female must be post-menopausal for at least 1 year or surgically sterile 9. Participants must be in general good health\* based on medical history and physical examination, as determined by the PI at Screening. 10. Participants must agree to refrain from donating blood, plasma, ova, sperm, or organs during the whole study.
Exclusion criteria
Participants who meet any of the following criteria are not eligible to participate in the study: 1. History of a systemic hypersensitivity or life-threatening reaction to a vaccine containing any of the same or similar substances. 2. History of test-confirmed by PCR or rapid antigen test to SARS-CoV-2 COVID-19 infection within 3 months prior to randomisation. 3. Presence of clinically significant medical history\*, unstable chronic or acute disease that, in the opinion of the PI, may increase the risk of exposure to the investigational vaccine 4. History of having any significant side effects after receipt of any other COVID-19 vaccine eg. endocarditis, pericarditis or myocarditis. History of any severe reactogenic side effects or other medical illness that were thought to be associated with vaccine. 5. Presence of an acute illness\* or with fever at 38.00 C or more within 72 hours prior to vaccination. 6. Bleeding disorders or taking an anticoagulant or anti-platelet agent that may contraindicate for intramuscular injection based on Investigator's judgment 7. Inadequate venous access to allow the collection of blood samples. 8. Received any prophylactic or therapeutic vaccine, biologic product, device or blood product, within 4 weeks of vaccination or 5 half-lives (whichever is longer) or anticipate doing so in the follow-up period defined for this study. For influenza vaccine, however, can be administered up to 14 days prior to randomization and following visit 3 (Day 29+3) after blood sample collection. 9. History of ever had an anaphylaxis reaction to food, medication, or vaccination. 10. Participant is immunosuppressed as caused by disease or immunosuppressive therapy or anticipated need to use of any chemotherapy or immunosuppressive agents\* within the next 6 months. 11. Participation in any of the other investigational trials of vaccines, therapeutic, or medical devices 12 weeks before or during the 6 months of this study. 12. Received immunoglobulins and/or any blood or blood products within 3 months before vaccination day or plans to receive any blood or blood products at any time during the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| adverse events | 30 minutes after vaccination | Presence of immediate adverse events within 30 minutes after vaccination |
| solicited injection site or systemic reactions | within 7 days after vaccination | Presence of solicited injection site or systemic reactions within 7 days after vaccination |
| unsolicited adverse events | within 28 days after vaccination | Presence of unsolicited adverse events within 28 days after vaccination |
| serious adverse events (SAEs) | 169 days | Presence of serious adverse events (SAEs) from day 1 to Day 169 |
| medically attended adverse events (MAAEs) | 169 days | Presence of medically attended adverse events (MAAEs) from day 1 to Day 169 |
| New Onset Chronic Medical Condition (NOCMCs) | 169 days | Presence of New Onset Chronic Medical Condition (NOCMCs) from day 1 to Day 169 |
| vital signs | 169 days | Number of participants with abnormal vital signs |
| clinical changes | 169 days | Number of participants with abnormal physical examinations finding |
| Geometric mean titers of neutralizing antibody titer | Day 29 | Geometric mean titers of neutralizing antibody titer measured by pseudoviral neutralization assay (psVNT-50) against Omicron BA.4/BA.5 exposed to COMVIGEN (Bivalent) vaccine |
| Geometric mean of the fold-rise post-vaccination of psVNT-50 neutralizing antibody titer | Day 29 | Geometric mean of the fold-rise post-vaccination of psVNT-50 neutralizing antibody titer against wild-type virus exposed to COMVIGEN (Bivalent) vaccine |
| Proportion of participants with at least 4-fold-rise in neutralizing antibody titer | Day 29 | Proportion of participants with at least 4-fold-rise in neutralizing antibody titer, psVNT-50 against wild-type virus exposed to COMVIGEN (Bivalent) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| median number of SARS-CoV2-specific T-cell responses | Day 1 | median number of SARS-CoV2-specific T-cell responses (spot-forming cells or SFC per 1 million PBMCs) measured by IFN gamma-ELISPOT assay against wild-type peptides at day 1 |
| Geometric mean titers of neutralizing antibody titer | Day 29 | Geometric mean titers of neutralizing antibody titer at Day 29 measured by psVNT-50 against other relevant variants of concerns (VOCs) |
| Geometric mean of the fold-rise post-vaccination of SARS-CoV2-specific T-cell responses | Day 29 | Geometric mean of the fold-rise post-vaccination of SARS-CoV2-specific T-cell responses (spot-forming cells (SFC) per 1 million PBMCs) measured by IFN gamma-ELISPOT assay against wild-type peptides exposed to COMVIGEN (Bivalent) vaccine on Day 29 |
| Geometric mean of the fold-rise post-vaccination of psVNT-50 neutralizing antibody titer | Day 29 | Geometric mean of the fold-rise post-vaccination of psVNT-50 neutralizing antibody titer against other relevant VOCs from Day 1 to Day 29 |
| Proportion of participants with at least 4-fold-rise in neutralization antibody titer | Day 29 | Proportion of participants with at least 4-fold-rise in neutralization antibody titer, psVNT-50 against other relevant VOCs from Day 1 to Day 29 |
| Geometric mean of the fold-rise post-vaccination of micro-VNT-50 | Day 29 | Geometric mean of the fold-rise post-vaccination of micro-VNT-50 against wild-type on Day 29. |
| Proportion of participants with at least 4-fold-rise in micro-VNT-50 | Day 29 | Proportion of participants with at least 4-fold-rise in micro-VNT-50 against wild-type virus on Day 29. |
| Geometric mean titers of anti-RBD antibody titer | Day 29 | Geometric mean titers of anti-RBD antibody titer at Day 29 against wild type. |
| Geometric mean titers of anti-Spike (S) antibody titer | Day 29 | Geometric mean titers of anti-Spike (S) antibody titer at Day 29 against wild type. |
| Geometric mean of the fold-rise post-vaccination of anti-RBD antibody | Day 29 | Geometric mean of the fold-rise post-vaccination of anti-RBD antibody against wild-type virus at Day 29. |
| Geometric mean of the fold-rise post-vaccination of anti-S antibody titer | Day 29 | Geometric mean of the fold-rise post-vaccination of anti-S antibody titer against wild-type virus at Day 29. |
| Proportion of participants with at least 4-fold-rise in anti-RBD | Day 29 | Proportion of participants with at least 4-fold-rise in anti-RBD titer against wild-type virus at Day 29 |
| Geometric mean of SARS-CoV2-specific T-cell responses | Day 1 | Geometric mean of SARS-CoV2-specific T-cell responses (spot-forming cells or SFC per 1 million PBMCs) measured by IFN gamma-ELISPOT assay against wild-type peptides at day 1 |
Countries
Thailand
Contacts
Primary ContactWatsamon Jantarabenjakul, MD
Outcome results
None listed