Safety and Immunogenicity of ChulaCov19 BNA159 mRNA Vaccine

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

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

Study Overview

• Status: Recruiting
• Conditions: 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: Biological: ChulaCov19 BNA159 mRNA vaccine

Detailed Description

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) .

• Study Type: Interventional
• Enrollment (Anticipated): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• Thailand
  • Bangkok, Thailand, 10330
    • Recruiting
    • Chula Clinical Research Center (Chula CRC), Faculty of Medicine, Chulalongkorn University
  • Khon Kaen, Thailand
    • Recruiting
    • Academic Clinical Research Office (ACRO) Faculty of Medicine, Khon Kaen University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female participants between the ages of 18 and 60 years, inclusive, at enrolment

2. Women of child-bearing potential (WOCBP) may be enrolled in the study if the participant fulfils all the following criteria:

   1. Has a negative urine-based pregnancy test at screening and on the day of the first dose (Day1) and second dose (Day22)
   2. 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.
   3. Is not currently breastfeeding.

3. 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).

4. 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:

5. Participants must be able to communicate effectively with study personnel and agree to comply with the study procedures.
6. Capable to provide written informed consent.
7. 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.

8. 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:

9. 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.
10. Known infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV).
11. History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention(s).
12. Participant has previously participated in an investigational study involving LNPs (a component of the investigational vaccine assessed in this trial).
13. 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.
14. Close contact with anyone known to have SARS-CoV-2 infection within 10 days prior to vaccine administration.

15. 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:

16. 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.
17. Receipt of medications intended to prevent COVID-19.
18. 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.

19. Receipt of immunoglobulins or blood products within 3 months of first vaccination.

    Diagnostic Assessments:

20. Positive on SAR-CoV-2 -RBD and/or -N antibody IgG/IgM at screening visit

21. Positive test for HIV, hepatitis B surface antigen (HBsAg) or hepatitis C virus antibodies (HCV Abs) at the screening visit.

    Other Exclusions:

22. 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).
23. Participation in other studies involving study intervention within 28 days prior to study entry and/or during study participation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: NON_RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: NONE

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric mean titres (GMT)	SARS-CoV-2- specific Pseudo-virus neutralization test with 50% inhibition titer (psVNT50) against wild type virus (WT)	at Day 50 (±3)
Proportion of participants who achieved a greater than or equal to 4-fold rise from before vaccination to Day 50 (±3)	SARS-CoV-2- specific Pseudo-virus neutralization test with 50% inhibition titer (psVNT50) against wild type virus (WT)	before vaccination to Day 50 (±3)
Geometric mean ratio (GMR) defined as GMT ratio between the two doses of ChulaCov19 BNA159 mRNA vaccine	SARS-CoV-2- specific Pseudo-virus neutralization test with 50% inhibition titer (psVNT50) against wild type virus (WT)	at Day 50 (±3)
Geometric mean titres (GMT)	SARS-CoV-2- specific Pseudo-virus neutralization test with 50% inhibition titer (psVNT50) against WT and variants of concern including Delta and Omicron	Day 29 (+3)
Geometric mean titres (GMT)	SARS-CoV-2- specific Pseudo-virus neutralization test with 50% inhibition titer (psVNT50) against WT and variants of concern including Delta and Omicron	Day 50 (±3)
Geometric mean titres (GMT)	SARS-CoV-2- specific Pseudo-virus neutralization test with 50% inhibition titer (psVNT50) against WT and variants of concern including Delta and Omicron	Day 112 (±7)
Geometric mean titres (GMT)	SARS-CoV-2- specific Pseudo-virus neutralization test with 50% inhibition titer (psVNT50) against WT and variants of concern including Delta and Omicron	Day 202 (±7)
Geometric mean titres (GMT)	SARS-CoV-2- specific Pseudo-virus neutralization test with 50% inhibition titer (psVNT50) against WT and variants of concern including Delta and Omicron	Day387 ±14
Proportion of participants who achieved a greater than or equal to 4-fold rise from before vaccination to Day 50 (±3)	SARS-CoV-2- specific Pseudo-virus neutralization test with 50% inhibition titer (psVNT50) against WT and variants of concern including Delta and Omicron	before vaccination to Day 50 (±3)
Geometric mean ratio (GMR) defined as GMT ratio between the two doses of ChulaCov19 BNA159 mRNA vaccine	SARS-CoV-2- specific Pseudo-virus neutralization test with 50% inhibition titer (psVNT50) against WT and variants of concern including Delta and Omicron	Day 29 (+3)
Geometric mean ratio (GMR) defined as GMT ratio between the two doses of ChulaCov19 BNA159 mRNA vaccine	SARS-CoV-2- specific Pseudo-virus neutralization test with 50% inhibition titer (psVNT50) against WT and variants of concern including Delta and Omicron	Day 50 (±3)
Geometric mean ratio (GMR) defined as GMT ratio between the two doses of ChulaCov19 BNA159 mRNA vaccine	SARS-CoV-2- specific Pseudo-virus neutralization test with 50% inhibition titer (psVNT50) against WT and variants of concern including Delta and Omicron	Day 112 (±7)
Geometric mean ratio (GMR) defined as GMT ratio between the two doses of ChulaCov19 BNA159 mRNA vaccine	SARS-CoV-2- specific Pseudo-virus neutralization test with 50% inhibition titer (psVNT50) against WT and variants of concern including Delta and Omicron	Day 202 (±7)
Geometric mean ratio (GMR) defined as GMT ratio between the two doses of ChulaCov19 BNA159 mRNA vaccine	SARS-CoV-2- specific Pseudo-virus neutralization test with 50% inhibition titer (psVNT50) against WT and variants of concern including Delta and Omicron	Day387 ±14
Geometric mean titres (GMT)	SARS-CoV-2- specific Live-virus neutralization test with 50% inhibition titer (MicroVNT50) against wild type virus (WT)	at Day 29 (+3)
Geometric mean titres (GMT)	SARS-CoV-2- specific Live-virus neutralization test with 50% inhibition titer (MicroVNT50) against wild type virus (WT)	at Day 50 (±3)
Proportion of participants who achieved a greater than or equal to 4-fold rise from before vaccination to Day 50 (±3)	SARS-CoV-2- specific Live-virus neutralization test with 50% inhibition titer (MicroVNT50) against wild type virus (WT)	before vaccination to Day 50 (±3)
Geometric mean ratio (GMR) defined as GMT ratio between the two doses of ChulaCov19 BNA159 mRNA vaccine at Day 50 (±3)	SARS-CoV-2- specific Live-virus neutralization test with 50% inhibition titer (MicroVNT50) against wild type virus (WT)	at Day 50 (±3)
Geometric mean titres (GMT)	SARS-CoV-2-surrogate viral neutralising antibody as measured by surrogate viral neutralising antibody assay (sVNT)	at Day22
Geometric mean titres (GMT)	SARS-CoV-2-surrogate viral neutralising antibody as measured by surrogate viral neutralising antibody assay (sVNT)	at Day 29 (+3)
Geometric mean titres (GMT)	SARS-CoV-2-surrogate viral neutralising antibody as measured by surrogate viral neutralising antibody assay (sVNT)	at Day 50 (±3)
Geometric mean titres (GMT)	SARS-CoV-2-surrogate viral neutralising antibody as measured by surrogate viral neutralising antibody assay (sVNT)	at Day 112 (±7)
Geometric mean titres (GMT)	SARS-CoV-2-surrogate viral neutralising antibody as measured by surrogate viral neutralising antibody assay (sVNT)	at Day 202 (±7)
Geometric mean titres (GMT)	SARS-CoV-2-surrogate viral neutralising antibody as measured by surrogate viral neutralising antibody assay (sVNT)	at Day387 ±14
Proportion of participants who achieved a greater than or equal to 4-fold rise from before vaccination to Day 50 (±3)	SARS-CoV-2-surrogate viral neutralising antibody as measured by surrogate viral neutralising antibody assay (sVNT)	before vaccination to Day 50 (±3)
Geometric mean ratio (GMR) defined as GMT ratio between the two doses of ChulaCov19 BNA159 mRNA vaccine at Day 50 (±3)	SARS-CoV-2-surrogate viral neutralising antibody as measured by surrogate viral neutralising antibody assay (sVNT)	at Day 50 (±3)
Geometric mean titres (GMT)	SARS-Cov2-RBD-binding IgG antibody measured by enzyme-linked immunosorbent assay (ELISA)	at Day22
Geometric mean titres (GMT)	SARS-Cov2-RBD-binding IgG antibody measured by enzyme-linked immunosorbent assay (ELISA)	at Day 50 (±3)
Geometric mean titres (GMT)	SARS-Cov2-RBD-binding IgG antibody measured by enzyme-linked immunosorbent assay (ELISA)	at Day 112 (±7)
Geometric mean titres (GMT)	SARS-Cov2-RBD-binding IgG antibody measured by enzyme-linked immunosorbent assay (ELISA)	at Day 202 (±7)
Geometric mean titres (GMT)	SARS-Cov2-RBD-binding IgG antibody measured by enzyme-linked immunosorbent assay (ELISA)	Day387 ±14
Proportion of participants who achieved a greater than or equal to 4-fold rise from before vaccination to Day 50 (±3)	SARS-Cov2-RBD-binding IgG antibody measured by enzyme-linked immunosorbent assay (ELISA)	before vaccination to Day 50 (±3)
Geometric mean ratio (GMR) defined as GMT ratio between the two doses of ChulaCov19 BNA159 mRNA vaccine at Day 50 (±3)	SARS-Cov2-RBD-binding IgG antibody measured by enzyme-linked immunosorbent assay (ELISA)	at Day 50 (±3)
Geometric mean titres (GMT) of IgG	SARS-Cov2-spike protein-binding IgG antibody measured by enzyme-linked immunosorbent assay (ELISA)	at Day22
Geometric mean titres (GMT) of IgG	SARS-Cov2-spike protein-binding IgG antibody measured by enzyme-linked immunosorbent assay (ELISA)	at Day 29 (+3)
Geometric mean titres (GMT) of IgG	SARS-Cov2-spike protein-binding IgG antibody measured by enzyme-linked immunosorbent assay (ELISA)	at Day 50 (±3)
Proportion of participants who achieved a greater than or equal to 4-fold rise from before vaccination to Day 50 (±3)	SARS-Cov2-spike protein-binding IgG antibody measured by enzyme-linked immunosorbent assay (ELISA)	before vaccination to Day 50 (±3)
Geometric mean ratio (GMR) defined as GMT ratio between the two doses of ChulaCov19 BNA159 mRNA vaccine at Day 50 (±3)	SARS-Cov2-spike protein-binding IgG antibody measured by enzyme-linked immunosorbent assay (ELISA)	at Day 50 (±3)
Percentage of participants who have positive specific T-cell IFNγ ELISpot responses (detectable above the assays cut-off)	SARS-CoV-2 spike protein-specific T-cell reposes as measured by IFNγ ELISpot assay	on Day 29 (+3)
Percentage of participants who have positive specific T-cell IFNγ ELISpot responses (detectable above the assays cut-off)	SARS-CoV-2 spike protein-specific T-cell reposes as measured by IFNγ ELISpot assay	on Day 50 (±3)
Percentage of participants who have positive specific T-cell IFNγ ELISpot responses (detectable above the assays cut-off)	SARS-CoV-2 spike protein-specific T-cell reposes as measured by IFNγ ELISpot assay	on Day 112 (±7)
Percentage of participants who have positive specific T-cell IFNγ ELISpot responses (detectable above the assays cut-off)	SARS-CoV-2 spike protein-specific T-cell reposes as measured by IFNγ ELISpot assay	on Day 202 (±7)
Median number of spot-forming cells (SFC) per 1 million PBMCs	SARS-CoV-2 spike protein-specific T-cell reposes as measured by IFNγ ELISpot assay	on Day 29 (+3)
Median number of spot-forming cells (SFC) per 1 million PBMCs	SARS-CoV-2 spike protein-specific T-cell reposes as measured by IFNγ ELISpot assay	on Day 50 (±3)
Median number of spot-forming cells (SFC) per 1 million PBMCs	SARS-CoV-2 spike protein-specific T-cell reposes as measured by IFNγ ELISpot assay	on Day 112 (±7)
Median number of spot-forming cells (SFC) per 1 million PBMCs	SARS-CoV-2 spike protein-specific T-cell reposes as measured by IFNγ ELISpot assay	on Day 202 (±7)
geometric mean of spot-forming cells (SFC) per 1 million PBMCs	SARS-CoV-2 spike protein-specific T-cell reposes as measured by IFNγ ELISpot assay	on Day 29 (+3)
geometric mean of spot-forming cells (SFC) per 1 million PBMCs	SARS-CoV-2 spike protein-specific T-cell reposes as measured by IFNγ ELISpot assay	on Day 50 (±3)
geometric mean of spot-forming cells (SFC) per 1 million PBMCs	SARS-CoV-2 spike protein-specific T-cell reposes as measured by IFNγ ELISpot assay	on Day 112 (±7)
geometric mean of spot-forming cells (SFC) per 1 million PBMCs	SARS-CoV-2 spike protein-specific T-cell reposes as measured by IFNγ ELISpot assay	on Day 202 (±7)
Percentage of participants who shows positive specific Th1 responses	SARS-CoV-2 spike protein-specific Th1/Th2 polarisation responses quantified by intracellular cytokine staining	on Day 29 (+3)
Percentage of participants who shows positive specific Th1 responses	SARS-CoV-2 spike protein-specific Th1/Th2 polarisation responses quantified by intracellular cytokine staining	on Day 50 (±3)
Median percentage specific Th1 responses, or Th2 response of each cohort	SARS-CoV-2 spike protein-specific Th1/Th2 polarisation responses quantified by intracellular cytokine staining	on Day 29 (+3)
Median percentage specific Th1 responses, or Th2 response of each cohort	SARS-CoV-2 spike protein-specific Th1/Th2 polarisation responses quantified by intracellular cytokine staining	on Day 50 (±3)

Collaborators and Investigators

• Sponsor: Chulalongkorn University
• Collaborators: BioNet-Asia; Chula Clinical Research Center (Chula CRC), Faculty of Medicine, Chulalongkorn University; Academic Clinical Research Office (ACRO), Faculty of Medicine, Khon Kaen University

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 14, 2022
• Primary Completion (ANTICIPATED): July 1, 2023
• Study Completion (ANTICIPATED): July 1, 2023

Study Registration Dates

• First Submitted: February 7, 2022
• First Submitted That Met QC Criteria: February 7, 2022
• First Posted (ACTUAL): February 9, 2022

Study Record Updates

• Last Update Posted (ACTUAL): February 10, 2023
• Last Update Submitted That Met QC Criteria: February 8, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: ChulaVac 003

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No