Clinical trial NCT05231369: Safety and Immunogenicity of ChulaCov19 BNA159 mRNA Vaccine
Official title: A Phase 1 Study to Evaluate Safety, Immunogenicity of the ChulaCov19 BNA159 mRNA Vaccine in Healthy Adults
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
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
Lead sponsor: Chulalongkorn University
Sponsor class: OTHER
Collaborators: name: Chula Clinical Research Center (Chula CRC), Faculty of Medicine, Chulalongkorn University
name: Academic Clinical Research Office (ACRO), Faculty of Medicine, Khon Kaen University
name: BioNet-Asia
First posted: 2022-02-09
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: If 25 ug dose is safe, then will proceed to enroll participants to receive 50 ug.
Primary purpose: PREVENTION

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

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) .

Eligibility criteria: 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.

Primary outcomes:
measure: Frequency of solicited local reactogenicity adverse events (AE)
timeFrame: during a 7-day follow-up period post each vaccination (up to Day 29+3)
measure: Grade of solicited local reactogenicity adverse events (AE)
timeFrame: during a 7-day follow-up period post each vaccination (up to Day 29+3)
measure: Frequency of solicited systemic reactogenicity adverse events (AE)
timeFrame: during a 7-day follow-up period post each vaccination (up to Day 29+3)
measure: Grade of solicited systemic reactogenicity adverse events (AE)
timeFrame: during a 7-day follow-up period post each vaccination (up to Day 29+3)
measure: Changes in vital signs
timeFrame: up to Visit 9 - Day 29 +3
measure: Changes in physical examinations
timeFrame: up to Visit 9 - Day 29 +3
measure: Clinically relevant changes in laboratory measurement
timeFrame: up to Visit 9 - Day 29 +3
measure: Treatment-emergent, clinically significant changes in vital signs
timeFrame: up to Visit 9 - Day 29 +3
measure: Treatment-emergent, clinically significant changes in physical examinations
timeFrame: up to Visit 9 - Day 29 +3
Secondary outcomes:
measure: Frequency of unsolicited AEs
timeFrame: up to Day 50 ±3
measure: Grade of unsolicited AEs
timeFrame: up to Day 50 ±3
measure: Frequency of SAEs
timeFrame: up to the end of the study Day387 ±14
measure: Frequency of MAAEs
timeFrame: up to the end of the study Day387 ±14
measure: Frequency of NOCMCs
timeFrame: up to the end of the study Day387 ±14
measure: Geometric mean titres (GMT)
timeFrame: at Day29 (+3)
measure: Proportion of participants who achieved a greater than or equal to 4-fold rise from before vaccination to Day29 (+3)
timeFrame: before vaccination to Day29 (+3)
measure: Geometric mean ratio (GMR) defined as GMT ratio between the two doses of ChulaCov19 BNA159 mRNA vaccine
timeFrame: at Day29 (+3)
Other outcomes:
measure: Geometric mean titres (GMT)
timeFrame: at Day 50 (±3)
measure: Proportion of participants who achieved a greater than or equal to 4-fold rise from before vaccination to Day 50 (±3)
timeFrame: before vaccination to Day 50 (±3)
measure: Geometric mean ratio (GMR) defined as GMT ratio between the two doses of ChulaCov19 BNA159 mRNA vaccine
timeFrame: at Day 50 (±3)
measure: Geometric mean titres (GMT)
timeFrame: Day 29 (+3)
measure: Geometric mean titres (GMT)
timeFrame: Day 50 (±3)
measure: Geometric mean titres (GMT)
timeFrame: Day 112 (±7)
measure: Geometric mean titres (GMT)
timeFrame: Day 202 (±7)
measure: Geometric mean titres (GMT)
timeFrame: Day387 ±14
measure: Proportion of participants who achieved a greater than or equal to 4-fold rise from before vaccination to Day 50 (±3)
timeFrame: before vaccination to Day 50 (±3)
measure: Geometric mean ratio (GMR) defined as GMT ratio between the two doses of ChulaCov19 BNA159 mRNA vaccine
timeFrame: Day 29 (+3)
measure: Geometric mean ratio (GMR) defined as GMT ratio between the two doses of ChulaCov19 BNA159 mRNA vaccine
timeFrame: Day 50 (±3)
measure: Geometric mean ratio (GMR) defined as GMT ratio between the two doses of ChulaCov19 BNA159 mRNA vaccine
timeFrame: Day 112 (±7)
measure: Geometric mean ratio (GMR) defined as GMT ratio between the two doses of ChulaCov19 BNA159 mRNA vaccine
timeFrame: Day 202 (±7)
measure: Geometric mean ratio (GMR) defined as GMT ratio between the two doses of ChulaCov19 BNA159 mRNA vaccine
timeFrame: Day387 ±14
measure: Geometric mean titres (GMT)
timeFrame: at Day 29 (+3)
measure: Geometric mean titres (GMT)
timeFrame: at Day 50 (±3)
measure: Proportion of participants who achieved a greater than or equal to 4-fold rise from before vaccination to Day 50 (±3)
timeFrame: before vaccination to Day 50 (±3)
measure: Geometric mean ratio (GMR) defined as GMT ratio between the two doses of ChulaCov19 BNA159 mRNA vaccine at Day 50 (±3)
timeFrame: at Day 50 (±3)
measure: Geometric mean titres (GMT)
timeFrame: at Day22
measure: Geometric mean titres (GMT)
timeFrame: at Day 29 (+3)
measure: Geometric mean titres (GMT)
timeFrame: at Day 50 (±3)
measure: Geometric mean titres (GMT)
timeFrame: at Day 112 (±7)
measure: Geometric mean titres (GMT)
timeFrame: at Day 202 (±7)
measure: Geometric mean titres (GMT)
timeFrame: at Day387 ±14
measure: Proportion of participants who achieved a greater than or equal to 4-fold rise from before vaccination to Day 50 (±3)
timeFrame: before vaccination to Day 50 (±3)
measure: Geometric mean ratio (GMR) defined as GMT ratio between the two doses of ChulaCov19 BNA159 mRNA vaccine at Day 50 (±3)
timeFrame: at Day 50 (±3)
measure: Geometric mean titres (GMT)
timeFrame: at Day22
measure: Geometric mean titres (GMT)
timeFrame: at Day 50 (±3)
measure: Geometric mean titres (GMT)
timeFrame: at Day 112 (±7)
measure: Geometric mean titres (GMT)
timeFrame: at Day 202 (±7)
measure: Geometric mean titres (GMT)
timeFrame: Day387 ±14
measure: Proportion of participants who achieved a greater than or equal to 4-fold rise from before vaccination to Day 50 (±3)
timeFrame: before vaccination to Day 50 (±3)
measure: Geometric mean ratio (GMR) defined as GMT ratio between the two doses of ChulaCov19 BNA159 mRNA vaccine at Day 50 (±3)
timeFrame: at Day 50 (±3)
measure: Geometric mean titres (GMT) of IgG
timeFrame: at Day22
measure: Geometric mean titres (GMT) of IgG
timeFrame: at Day 29 (+3)
measure: Geometric mean titres (GMT) of IgG
timeFrame: at Day 50 (±3)
measure: Proportion of participants who achieved a greater than or equal to 4-fold rise from before vaccination to Day 50 (±3)
timeFrame: before vaccination to Day 50 (±3)
measure: Geometric mean ratio (GMR) defined as GMT ratio between the two doses of ChulaCov19 BNA159 mRNA vaccine at Day 50 (±3)
timeFrame: at Day 50 (±3)
measure: Percentage of participants who have positive specific T-cell IFNγ ELISpot responses (detectable above the assays cut-off)
timeFrame: on Day 29 (+3)
measure: Percentage of participants who have positive specific T-cell IFNγ ELISpot responses (detectable above the assays cut-off)
timeFrame: on Day 50 (±3)
measure: Percentage of participants who have positive specific T-cell IFNγ ELISpot responses (detectable above the assays cut-off)
timeFrame: on Day 112 (±7)
measure: Percentage of participants who have positive specific T-cell IFNγ ELISpot responses (detectable above the assays cut-off)
timeFrame: on Day 202 (±7)
measure: Median number of spot-forming cells (SFC) per 1 million PBMCs
timeFrame: on Day 29 (+3)
measure: Median number of spot-forming cells (SFC) per 1 million PBMCs
timeFrame: on Day 50 (±3)
measure: Median number of spot-forming cells (SFC) per 1 million PBMCs
timeFrame: on Day 112 (±7)
measure: Median number of spot-forming cells (SFC) per 1 million PBMCs
timeFrame: on Day 202 (±7)
measure: geometric mean of spot-forming cells (SFC) per 1 million PBMCs
timeFrame: on Day 29 (+3)
measure: geometric mean of spot-forming cells (SFC) per 1 million PBMCs
timeFrame: on Day 50 (±3)
measure: geometric mean of spot-forming cells (SFC) per 1 million PBMCs
timeFrame: on Day 112 (±7)
measure: geometric mean of spot-forming cells (SFC) per 1 million PBMCs
timeFrame: on Day 202 (±7)
measure: Percentage of participants who shows positive specific Th1 responses
timeFrame: on Day 29 (+3)
measure: Percentage of participants who shows positive specific Th1 responses
timeFrame: on Day 50 (±3)
measure: Median percentage specific Th1 responses, or Th2 response of each cohort
timeFrame: on Day 29 (+3)
measure: Median percentage specific Th1 responses, or Th2 response of each cohort
timeFrame: on Day 50 (±3)
Locations:
city: Bangkok
country: Thailand
facility: Chula Clinical Research Center (Chula CRC), Faculty of Medicine, Chulalongkorn University
city: Khon Kaen
country: Thailand
facility: Academic Clinical Research Office (ACRO) Faculty of Medicine, Khon Kaen University
Study officials:
affiliation: HIV-NAT, Thai Red Cross - AIDS Research Centre
name: Sivaporn Gatechompol, MD
role: PRINCIPAL_INVESTIGATOR
References: