Safety and Immunogenicity of ChulaCov19 BNA159 mRNA Vaccine

Study Overview
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Brief Summary
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This is a phase 1 study that will evaluate the safety and immunogenicity of ChulaCov19 BNA159 mRNA vaccine in healthy adults.

Detailed Description
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ChulaCov19 BNA159 mRNA vaccine is the lipid nanoparticles (LNPs)-encapsulated mRNA-based ChulaCov19 vaccine developed by Chula VRC and manufactured by BioNet Asia, Thailand for the active immunisation of healthy adults against coronavirus disease 2019 (COVID-19). This is a phase 1 study that will evaluate the safety and immunogenicity of ChulaCov19 BNA159 mRNA vaccine in healthy adults. This study will be conducted in 2 study centers, open-label , dose finding, first in human (FIH) study conducted in healthy participants. There are two groups. One group will receive 25 ug of ChulaCov19 BNA159 mRNA vaccine and the other group will receive 50 ug of ChulaCov19 BNA159 mRNA vaccine. Each group will have 12 participants. Intramuscular injection of the investigational vaccine at the assigned dose, will be administered 21 days apart, on Day 1 and Day 22 ( ±3) .

Official Title
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A Phase 1 Study to Evaluate Safety, Immunogenicity of the ChulaCov19 BNA159 mRNA Vaccine in Healthy Adults

Conditions
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Safety of 25 ug of ChulaCov19-BNA159 mRNA Vaccine, Tolerability of 25 ug of ChulaCov19-BNA159 mRNA Vaccine, Immune Response of 25 ug of ChulaCov19-BNA159 mRNA Vaccine, Safety of 50 ug of ChulaCov19-BNA159 mRNA Vaccine, Tolerability of 50 ug of ChulaCov19-BNA159 mRNA Vaccine, Immune Response of 50 ug of ChulaCov19-BNA159 mRNA Vaccine, Assess Which Dose is Appropriate to Use

Intervention / Treatment
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* Biological: ChulaCov19 BNA159 mRNA vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female participants between the ages of 18 and 60 years, inclusive, at enrolment Women of child-bearing potential (WOCBP) may be enrolled in the study if the participant fulfils all the following criteria: Has a negative urine-based pregnancy test at screening and on the day of the first dose (Day1) and second dose (Day22) Must practice true abstinence or, if engaged in sexual relations with a male, they must agree to use highly effective (failure rate of < 1% per year when used consistently and correctly), double-barrier contraceptive measures* from screening and for a period of at least 60 days after the last dose of investigational vaccine. Is not currently breastfeeding. Women of non-child-bearing potential may be enrolled in the study if the participant meet one of these following criteria: d. Postmenopausal (defined as having a history of amenorrhea of at least one year), or e. History of amenorrhea is less than one year, must have an FSH level > 40 milli-international units per milliliter (mIU/mL), or f. Have a documented status of being surgically sterile (hysterectomy, bilateral oophorectomy, or tubal ligation/salpingectomy). 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 the last dose of investigational vaccine. * The PI is to assess the adequacy of methods of contraception on a case-by-case basis. These criteria do not apply if the participants are in a same-sex relationship. Type of Participant and Disease Characteristics: Participants must be able to communicate effectively with study personnel and agree to comply with the study procedures. Capable to provide written informed consent. Healthy participants who are determined by medical history, physical examination (if required), and clinical judgment of the investigator to be eligible for inclusion in the study. Participants must have haematology, clinical chemistry, coagulation and urinalysis test results that are not deviating from the normal reference range by age and gender to a clinically relevant extent at Screening. Exclusion Criteria: Presence of clinically significant medical history, unstable chronic or acute disease, or physical, or laboratory findings that, in the opinion of the PI may potentially increase the expected risk of exposure to the investigational vaccine, compromise the safety of the participant, or interfere with any aspect of study conduct or interpretation of results. This will include any thrombocytopenia or bleeding disorder contraindicating IM vaccination. Known infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV). History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention(s). Participant has previously participated in an investigational study involving LNPs (a component of the investigational vaccine assessed in this trial). Previous clinical (based on COVID-19 symptoms/signs alone, if a SARS-CoV-2 NAAT result was not available) or microbiological (based on COVID-19 symptoms/signs and a positive SARS-CoV-2 NAAT result) diagnosis of COVID-19. Close contact with anyone known to have SARS-CoV-2 infection within 10 days prior to vaccine administration. Individuals at high risk for severe COVID-19, including those with any of the following risk factors: Uncontrolled hypertension Diabetes mellitus Cardiovascular disease Chronic pulmonary disease Asthma Chronic liver disease Stage 3 or worse chronic kidney disease (glomerular filtration rate <60 mL/min/1.73 m2) BMI >30 kg/m2 Individuals with a history of autoimmune disease Prior/Concomitant Therapy: Previous vaccination with any coronavirus vaccine at any time prior to the study or planned receipt of any other licensed or experimental SARS-CoV-2 vaccine within 50 days of receipt of the first study vaccination. Receipt of medications intended to prevent COVID-19. Chronic use (more than 14 continuous days) of or anticipated need to use, within the next 6 months, of any medications that may be associated with impaired immune responsiveness or with immunosuppression. Receipt of immunoglobulins or blood products within 3 months of first vaccination. Diagnostic Assessments: Positive on SAR-CoV-2 -RBD and/or -N antibody IgG/IgM at screening visit Positive test for HIV, hepatitis B surface antigen (HBsAg) or hepatitis C virus antibodies (HCV Abs) at the screening visit. Other Exclusions: Is a participant at high risk of SARS-CoV-2 exposure in the opinion of the PI (e.g., healthcare workers, active health care workers with direct patient contact, emergency response personnel). Participation in other studies involving study intervention within 28 days prior to study entry and/or during study participation.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: If 25 ug dose is safe, then will proceed to enroll participants to receive 50 ug.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: group 1: 25 ug of ChulaCov19 BNA159 mRNA vaccine<br>The participants will receive 25 ug of the vaccine. | Biological: ChulaCov19 BNA159 mRNA vaccine<br>* ChulaCov19 BNA159 mRNA vaccine is the lipid nanoparticles (LNPs)-encapsulated mRNA-based ChulaCov19 vaccine<br>|
| Experimental: group 2: 50 ug of ChulaCov19 BNA159 mRNA vaccine<br>If 25 ug is safe, then will proceed to enroll 12 more participants to receive 50 ug. | Biological: ChulaCov19 BNA159 mRNA vaccine<br>* ChulaCov19 BNA159 mRNA vaccine is the lipid nanoparticles (LNPs)-encapsulated mRNA-based ChulaCov19 vaccine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of solicited local reactogenicity adverse events (AE) | Frequency of solicited local reactogenicity adverse events (AE) during a 7-day follow-up period post each vaccination (up to Day 29+3) | during a 7-day follow-up period post each vaccination (up to Day 29+3) | 
| Grade of solicited local reactogenicity adverse events (AE) | Grade of solicited local reactogenicity adverse events (AE) during a 7-day follow-up period post each vaccination (up to Day 29+3) | during a 7-day follow-up period post each vaccination (up to Day 29+3) | 
| Frequency of solicited systemic reactogenicity adverse events (AE) | Frequency of solicited systemic reactogenicity adverse events (AE) during a 7-day follow-up period post each vaccination (up to Day 29+3) | during a 7-day follow-up period post each vaccination (up to Day 29+3) | 
| Grade of solicited systemic reactogenicity adverse events (AE) | Grade of solicited systemic reactogenicity adverse events (AE) during a 7-day follow-up period post each vaccination (up to Day 29+3) | during a 7-day follow-up period post each vaccination (up to Day 29+3) | 
| Changes in vital signs | Changes in vital signs | up to Visit 9 - Day 29 +3 | 
| Changes in physical examinations | Changes in physical examinations | up to Visit 9 - Day 29 +3 | 
| Clinically relevant changes in laboratory measurement | Clinically relevant changes in laboratory measurement | up to Visit 9 - Day 29 +3 | 
| Treatment-emergent, clinically significant changes in vital signs | Treatment-emergent, clinically significant changes in vital signs | up to Visit 9 - Day 29 +3 | 
| Treatment-emergent, clinically significant changes in physical examinations | Treatment-emergent, clinically significant changes in physical examinations | up to Visit 9 - Day 29 +3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of unsolicited AEs | Frequency of unsolicited AEs | up to Day 50 ±3 | 
| Grade of unsolicited AEs | Grade of unsolicited AEs | up to Day 50 ±3 | 
| Frequency of SAEs | Frequency of SAEs | up to the end of the study Day387 ±14 | 
| Frequency of MAAEs | Frequency of MAAEs | up to the end of the study Day387 ±14 | 
| Frequency of NOCMCs | Frequency of NOCMCs | up to the end of the study Day387 ±14 | 
| Geometric mean titres (GMT) | SARS-Cov2-RBD-binding IgG antibody measured by enzyme-linked immunosorbent assay (ELISA) | at Day29 (+3) | 
| Proportion of participants who achieved a greater than or equal to 4-fold rise from before vaccination to Day29 (+3) | SARS-Cov2-RBD-binding IgG antibody measured by enzyme-linked immunosorbent assay (ELISA) | before vaccination to Day29 (+3) | 
| Geometric mean ratio (GMR) defined as GMT ratio between the two doses of ChulaCov19 BNA159 mRNA vaccine | SARS-Cov2-RBD-binding IgG antibody measured by enzyme-linked immunosorbent assay (ELISA) | at Day29 (+3) |