Clinical trial NCT05930730: Immunogenicity and Safety of Comvigen (Bivalent) Vaccine
Official title: A Phase 2, Non-inferiority, Open-label, Randomized Controlled Study to Evaluate the Immunogenicity and Safety of Comvigen (Bivalent) Vaccine as a Booster Dose in Adults Who Have Received a Previous Booster Dose of an Approved COVID-19 Vaccine
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Safety of a Single Dose of COMVIGEN Vaccine
Reactogenicity of a Single Dose of COMVIGEN Vaccine
Immunogenicity of a Single Dose of COMVIGEN Vaccine
Safety of a Single Dose of BIVALENT Pfizer/BNT Vaccine
Reactogenicity of a Single Dose of BIVALENT Pfizer/BNT Vaccine
Immunogenicity of a Single Dose of BIVALENT Pfizer/BNT Vaccine
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
Lead sponsor: Chulalongkorn University
Sponsor class: OTHER
Collaborators: name: Chula Clinical Research Center (Chula CRC), Faculty of Medicine Chulalongkorn University, Bangkok, Thailand
name: HIV-NAT, Thai Red Cross - AIDS Research Centre
First posted: 2023-07-05
Enrollment: 450
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

Eligibility criteria: 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.

Primary outcomes:
measure: adverse events
timeFrame: 30 minutes after vaccination
measure: solicited injection site or systemic reactions
timeFrame: within 7 days after vaccination
measure: unsolicited adverse events
timeFrame: within 28 days after vaccination
measure: serious adverse events (SAEs)
timeFrame: 169 days
measure: medically attended adverse events (MAAEs)
timeFrame: 169 days
measure: New Onset Chronic Medical Condition (NOCMCs)
timeFrame: 169 days
measure: vital signs
timeFrame: 169 days
measure: vital signs
timeFrame: 169 days
measure: clinical changes
timeFrame: 169 days
measure: clinical changes
timeFrame: 169 days
measure: Geometric mean titers of neutralizing antibody titer
timeFrame: Day 29
measure: Geometric mean titers of neutralizing antibody titer
timeFrame: Day 29
measure: Geometric mean titers of neutralizing antibody titer
timeFrame: Day 29
measure: Geometric mean titers of neutralizing antibody titer
timeFrame: Day 29
measure: Geometric mean of the fold-rise post-vaccination of psVNT-50 neutralizing antibody titer
timeFrame: Day 29
measure: Geometric mean of the fold-rise post-vaccination of psVNT-50 neutralizing antibody titer
timeFrame: Day 29
measure: Geometric mean of the fold-rise post-vaccination of psVNT-50 neutralizing antibody titer
timeFrame: Day 29
measure: Geometric mean of the fold-rise post-vaccination of psVNT-50 neutralizing antibody titer
timeFrame: Day 29
measure: Proportion of participants with at least 4-fold-rise in neutralizing antibody titer
timeFrame: Day 29
measure: Proportion of participants with at least 4-fold-rise in neutralizing antibody titer
timeFrame: Day 29
measure: Proportion of participants with at least 4-fold-rise in neutralizing antibody titer
timeFrame: Day 29
measure: Proportion of participants with at least 4-fold-rise in neutralizing antibody titer
timeFrame: Day 29
Secondary outcomes:
measure: Geometric mean titers of neutralizing antibody titer
timeFrame: Day 29
measure: Geometric mean of the fold-rise post-vaccination of psVNT-50 neutralizing antibody titer
timeFrame: Day 29
measure: Proportion of participants with at least 4-fold-rise in neutralization antibody titer
timeFrame: Day 29
measure: Geometric mean titers of neutralizing antibody titer
timeFrame: Day 1
measure: Geometric mean titers of neutralizing antibody titer
timeFrame: Day 29
measure: Geometric mean titers of neutralizing antibody titer
timeFrame: Day 1
measure: Geometric mean titers of neutralizing antibody titer
timeFrame: Day 29
measure: Geometric mean of the fold-rise post-vaccination of micro-VNT-50
timeFrame: Day 29
measure: Geometric mean of the fold-rise post-vaccination of micro-VNT-50
timeFrame: Day 29
measure: Proportion of participants with at least 4-fold-rise in micro-VNT-50
timeFrame: Day 29
measure: Proportion of participants with at least 4-fold-rise in micro-VNT-50
timeFrame: Day 29
measure: Geometric mean titers of anti-RBD antibody titer
timeFrame: Day 29
measure: Geometric mean titers of anti-Spike (S) antibody titer
timeFrame: Day 29
measure: Geometric mean of the fold-rise post-vaccination of anti-RBD antibody
timeFrame: Day 29
measure: Geometric mean of the fold-rise post-vaccination of anti-S antibody titer
timeFrame: Day 29
measure: Proportion of participants with at least 4-fold-rise in anti-RBD
timeFrame: Day 29
measure: Proportion of participants with at least 4-fold-rise in anti-RBD
timeFrame: Day 29
measure: Geometric mean of SARS-CoV2-specific T-cell responses
timeFrame: Day 1
measure: Geometric mean of SARS-CoV2-specific T-cell responses
timeFrame: Day 29
measure: median number of SARS-CoV2-specific T-cell responses
timeFrame: Day 1
measure: median number of SARS-CoV2-specific T-cell responses
timeFrame: Day 29
measure: Geometric mean of the fold-rise post-vaccination of SARS-CoV2-specific T-cell responses
timeFrame: Day 29
measure: Geometric mean of the fold-rise post-vaccination of SARS-CoV2-specific T-cell responses
timeFrame: Day 29
Other outcomes:
Locations:
city: Bangkok
country: Thailand
facility: Department of Pediatric, Faculty of Medicine, Chulalongkorn University
city: Bangkok
country: Thailand
facility: HIV-NAT, Thai Red Cross - AIDS Research Centre
Study officials:
affiliation: Department of Pediatric, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
name: Watsamon Jantarabenjakul, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: HIVNAT, Thai Red Cross AIDS Research Centre, Bangkok, Thailand
name: Sivaporn Gatechompol, MD
role: PRINCIPAL_INVESTIGATOR
References: