A Study to Evaluate Safety, Tolerability, and Reactogenicity of an RBD-Fc-based Vaccine to Prevent COVID-19

A Phase 1, Randomized, Open-label, Dose-Finding Study to Evaluate the Safety, Tolerability, and Reactogenicity of Escalating Doses of the Baiya SARS-CoV-2 Vax 1 Vaccine in Healthy Adults

This study is a phase 1, open-label, randomized, first-in-human clinical trial to evaluate the safety, tolerability and reactogenicity of escalating doses of Baiya SARS-CoV-2 VAX1 vaccine in participants aged 18-60 for adult groups and 61-75 for elderly groups. Each group will consist of three cohorts to evaluate different doses (low, medium, high) of Baiya SARS-CoV-2 VAX vaccine. Participants will be injected with two doses of the investigational product with a 21-day interval.

Study Overview

• Status: Completed
• Conditions: Coronavirus
• Intervention / Treatment: Biological: Baiya SARS-CoV-2 Vax 1

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• Thailand
  • Bangkok, Thailand, 10330
    • Queen Saovabha Memorial Institute
  • Bangkok, Thailand, 10330
    • Chula Clinical Research Center (Chula CRC), Faculty of Medicine, Chulalongkorn University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy man and woman between 18-60 years old (inclusive) for the adult cohort and between 61-75 years old (inclusive) for the elderly cohort.
• Have a body-mass index of 18.0-30.0 kg/m² at screening
• Give informed consent prior to study enrollment and all study procedures
• Participants must be able to comply with study procedures and be available for all study visits
• Participants must be in general good health based on medical history and physical examination as determined by the investigator(s) at Screening
• Participants must have haematology, clinical chemistry, coagulation, and urinalysis test results that are not deviating from the normal reference range by age and gender, or considered "not clinicallysignificant" per investigator decision based on safety at Screening.
• Males must be surgically sterile (>30 days since vasectomy with no viable sperm), practice true abstinence, or, if engaged in sexual activities with a female with childbearing potential, use condoms from first vaccination until 60 days after the last vaccination.
• Females of child-bearing potential must practice true abstinence, or, if engaged in sexual activities with a male, agree to use highly effective (failure rate of <1% per year when used consistently and correctly), double-barrier contraceptive measures throughout the study and intend to continue use of contraception methods for at least 60 days following the last vaccination.
• Female participants of child-bearing potential must have negative serum pregnancy test by beta human chorionic gonadotropin [β-HCG] at Screening and a negative urine-based pregnancy test within 24 hours prior to each investigational vaccine administration
• Female participants of childbearing potential must not be pregnant or breastfeeding.

• Women of non-child-bearing potential must:

  1. be classified as being postmenopausal (defined as having a history of amenorrhea for at least one year), or
  2. where history of amenorrhea is less than one year, female participants must have a follicle stimulating hormone (FSH) level > 40 milli-international units per millilitre (mIU/mL), or
  3. have a documented status of being surgically sterile (hysterectomy, bilateral oophorectomy, or /salpingectomy).
• All volunteers will be screened for serum antibodies against SARS-CoV-2, as evidence of previous infection using Enzyme-Linked Immunosorbent Assay (ELISA) and must have a negative result
• Body temperature measured at forehead using validated device must be less than 37.5ºC at Screening.
• Pulse must be no greater than 100 beats per minute, at Screening
• Systolic blood pressure (SBP) must be between 85 to 150 millimeters of mercury (mm Hg), inclusive, at Screening
• Participants must agree to refrain from donating blood, plasma, ovules, sperm, or organs during the whole study

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.
• Presence of self-reported or medically documented significant medical or psychiatric condition(s) as judged by the investigator(s) that it may not be in the participant's interest to participate in the study.
• Presence of an acute illness, as determined by the participating Study Site investigator(s), with or without fever (forehead temperature measured by validated device ≥ 37.5 ºC) within 72 hours prior to each vaccination
• Presence of birthmarks, tattoos, wound, or other skin conditions over the deltoid region of both arms that in the opinion of the investigator(s), could reasonably obscure and interfere with evaluation of local ISRs
• Inadequate venous access to allow collection of blood samples
• Breastfeeding or planning to breastfeed from the time of the first vaccination to after the last vaccination, or pregnant as confirmed by a positive serum β-HCG pregnancy test at Screening or positive urine pregnancy test at subsequent clinic visits at timepoints as delineated in the schedule of assessments
• Received any prophylactic or therapeutic vaccine, or licensed or unlicensed vaccine, device, or blood product, within 4 weeks of first vaccination or 5 half-lives (whichever is longer), or anticipate to do so in the follow-up period defined for this study
• History of severe allergy (requiring hospital care), anaphylaxis, severe reaction to any drug or prior vaccination, or any known or suspected allergies or sensitivities to any component of the investigational vaccine or tobacco
• Participant is immunosuppressed as caused by disease (such as HIV)
• 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
• History of hepatitis B or hepatitis C infection
• Receipt of immunoglobulins or blood products within 90 days of the first vaccination
• Requirement for antipyretic or analgesic medication on a daily or every other day basis from enrolment through 72 hours after vaccination
• Current use of any prescription or over-the-counter medications within 7 days prior to vaccination, unless approved by the PI
• Receipt of other investigational products (drug, biologic or device) within 60 days before the first vaccination
• History of alcohol or drug abuse that in the opinion of the PI could affect the participant's safety or compliance with study
• Participant is unwilling to abstain from blood donation during the course of the study, and/or is participating in any research study involving blood sampling (more than 450 mL /unit of blood), or blood donation to any blood bank during the 2 months prior to the Screening visit
• Participant is unwilling to abstain from donating plasma, ovules, sperm, or organs during the course of the study
• Close contact with anyone known to have SARS-CoV-2 infection within 30 days prior to vaccine administration
• History of COVID-19 diagnosis
• Has a positive result on SARS-CoV-2 antibody IgG/IgM measured by ELISA at screening
• On current treatment with investigational agents for prophylaxis of COVID-19 including COVID-19 Vaccine under EUA.
• Planning to travel out of the country from enrolment through 29 days after the second vaccination
• Residing in a nursing home or other skilled nursing facility or having a requirement for skilled nursing care
• Is a participant at high risk of SARS-CoV2 exposure in the opinion of the PI, including but not limited to an occupation (e.g., healthcare workers, active health care workers with direct patient contact, emergency response personnel) or close contact with a SARS-CoV-2 positive confirmed case (e.g. family member, housemate)
• A chronic smoker (defined as ≥10 Pack years [packs/day × years smoked]) within the 12 months prior to enrolment (For Elderly Participants only)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 10 μg Baiya SARS-CoV-2 Vax 1, Adult Participants; 2 doses of Baiya SARS-CoV-2 Vax 1 (10 μg), each on Day 1 and Day 22 for adult participants (18 - 60 years old)	Biological: Baiya SARS-CoV-2 Vax 1; Intramuscular injection in the deltoid region of 0.5 mL/dose of Baiya SARS-CoV-2 Vax 1 (recombinant SARS-CoV-2 receptor-binding domain fused with FC region of human IgG1 vaccine)
Experimental: 50 μg Baiya SARS-CoV-2 Vax 1, Adult Participants; 2 doses of Baiya SARS-CoV-2 Vax 1 (50 μg), each on Day 1 and Day 22 for adult participants (18 - 60 years old)	Biological: Baiya SARS-CoV-2 Vax 1; Intramuscular injection in the deltoid region of 0.5 mL/dose of Baiya SARS-CoV-2 Vax 1 (recombinant SARS-CoV-2 receptor-binding domain fused with FC region of human IgG1 vaccine)
Experimental: 100 μg Baiya SARS-CoV-2 VAX1, Adult Participants; 2 doses of Baiya SARS-CoV-2 VAX1 (100 μg), each on Day 1 and Day 22 for adult participants (18 - 60 years old)	Biological: Baiya SARS-CoV-2 Vax 1; Intramuscular injection in the deltoid region of 0.5 mL/dose of Baiya SARS-CoV-2 Vax 1 (recombinant SARS-CoV-2 receptor-binding domain fused with FC region of human IgG1 vaccine)
Experimental: 10 μg Baiya SARS-CoV-2 VAX1, Elderly Participants; 2 doses of Baiya SARS-CoV-2 VAX1 (10 μg), each on Day 1 and Day 22 for elderly participants (61 - 75 years old)	Biological: Baiya SARS-CoV-2 Vax 1; Intramuscular injection in the deltoid region of 0.5 mL/dose of Baiya SARS-CoV-2 Vax 1 (recombinant SARS-CoV-2 receptor-binding domain fused with FC region of human IgG1 vaccine)
Experimental: 50 μg Baiya SARS-CoV-2 VAX1, Elderly Participants; 2 doses of Baiya SARS-CoV-2 VAX1 (50 μg), each on Day 1 and Day 22 for elderly participants (61 - 75 years old)	Biological: Baiya SARS-CoV-2 Vax 1; Intramuscular injection in the deltoid region of 0.5 mL/dose of Baiya SARS-CoV-2 Vax 1 (recombinant SARS-CoV-2 receptor-binding domain fused with FC region of human IgG1 vaccine)
Experimental: 100 μg Baiya SARS-CoV-2 VAX1, Elderly Participants; 2 doses of Baiya SARS-CoV-2 VAX1 (100 μg), each on Day 1 and Day 22 for elderly participants (61 - 75 years old)	Biological: Baiya SARS-CoV-2 Vax 1; Intramuscular injection in the deltoid region of 0.5 mL/dose of Baiya SARS-CoV-2 Vax 1 (recombinant SARS-CoV-2 receptor-binding domain fused with FC region of human IgG1 vaccine)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency and Grade of Solicited Adverse Events		7 days after each vaccination
Frequency and Grade of Adverse Events (including both solicited and unsolicited AEs)		Up to 28 days after second vaccination
Incidence of Serious Adverse Events (SAEs), Medically-Attended Adverse Events (MAAEs), and New-Onset Chronic Medical Conditions (NOCMCs)		Up to 28 days after second vaccination
Changes in Blood Pressure (Systolic and Diastolic Blood Pressure) from Baseline	Blood pressure is measured mmHg. Blood pressure, both systolic and diastolic, at multiple timepoints according to the protocol will be compared to baseline value. Changes in blood pressure will be described using descriptive statistic (mean, standard deviation).	Up to 28 days after second vaccination
Changes in Pulse Rate from Baseline	Pulse rate is measured as beats per minute. Pulse rate at multiple timepoints according to the protocol will be compared to baseline value. Changes in pulse rate will be described using descriptive statistic (mean, standard deviation).	Up to 28 days after second vaccination
Changes in Respiratory Rate from Baseline	Respiratory rate is measured as breaths per minute. Respiratory rate at multiple timepoints according to the protocol will be compared to baseline value. Changes in respiratory rate will be described using descriptive statistic (mean, standard deviation).	Up to 28 days after second vaccination
Changes in Body Temperature from Baseline	Body temperature is measured as degree Celsius. Body temperature at multiple timepoints according to the protocol will be compared to baseline value. Changes in body temperature will be described using descriptive statistic (mean, standard deviation)	Up to 28 days after second vaccination
Changes in Physical Conditions from Baseline Physical Examinations	Baseline physical examination will include head, ears, nose, throat, lungs, lymph nodes, heart, abdomen and skin. Symptom directed physical examination will be performed for each subsequent visit. Changes in physical conditions from baseline physical examination will be described.	Up to 28 days after second vaccination
Safety Laboratory Value (Haematology)	Haematology laboratory value by Common Terminology Criteria for Adverse Event (CTCAE) scale version 5.0 (absolute and change from baseline where identified). The scale ranges from Grade 1 (Mild) to Grade 5 (Most Severe).	Up to 28 days after second vaccination
Safety Laboratory Value (Serum chemistry)	Serum Chemistry laboratory value by Common Terminology Criteria for Adverse Event (CTCAE) scale version 5.0 (absolute and change from baseline where identified). The scale ranges from Grade 1 (Mild) to Grade 5 (Most Severe).	Up to 28 days after second vaccination
Safety Laboratory Value (Coagulation)	Coagulation laboratory value by Common Terminology Criteria for Adverse Event (CTCAE) scale version 5.0 (absolute and change from baseline where identified). The scale ranges from Grade 1 (Mild) to Grade 5 (Most Severe).	Up to 28 days after second vaccination
Safety Laboratory Value (Urinalysis)	Urinalysis laboratory value by Common Terminology Criteria for Adverse Event (CTCAE) scale version 5.0 (absolute and change from baseline where identified). The scale ranges from Grade 1 (Mild) to Grade 5 (Most Severe).	Up to 28 days after second vaccination
Treatment-emergent Changes in Blood Pressure	Grade of treatment-emergent changes in blood pressure by Common Terminology Criteria for Adverse Event (CTCAE) scale version 5.0. The scale ranges from Grade 1 (Mild) to Grade 5 (Most Severe).	Up to 28 days after second vaccination
Treatment-emergent Changes in Pulse Rate	Grade of treatment-emergent changes in pulse rate by Common Terminology Criteria for Adverse Event (CTCAE) scale version 5.0. The scale ranges from Grade 1 (Mild) to Grade 5 (Most Severe).	Up to 28 days after second vaccination
Treatment-emergent Changes in Respiratory Rate	Grade of treatment-emergent changes in respiratory rate by Common Terminology Criteria for Adverse Event (CTCAE) scale version 5.0. The scale ranges from Grade 1 (Mild) to Grade 5 (Most Severe).	Up to 28 days after second vaccination
Treatment-emergent Changes in Body Temperature	Grade of treatment-emergent changes in body temperature by Common Terminology Criteria for Adverse Event (CTCAE) scale version 5.0. The scale ranges from Grade 1 (Mild) to Grade 5 (Most Severe).	Up to 28 days after second vaccination
Treatment-emergent, Changes in Physical Conditions	Baseline physical examination will include head, ears, nose, throat, lungs, lymph nodes, heart, abdomen and skin. Symptom directed physical examination will be performed for each subsequent visit. Grade of treatment-emergent changes by Common Terminology Criteria for Adverse Event (CTCAE) scale version 5.0. The scale ranges from Grade 1 (Mild) to Grade 5 (Most Severe).	Up to 28 days after second vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency and Grade of Medically-Attended Adverse Events (MAAEs)		28 days - 1 year after second vaccination
Frequency and Grade of New-Onset Chronic Medical Conditions (NOCMCs)		28 days - 1 year after second vaccination
Incidence of SAEs		28 days - 1 year after second vaccination
Geometric Mean Titer (GMT) of SARS-CoV-2 Specific Serum Neutralising Antibody	SARS-CoV-2 Specific Serum Neutralising Antibody as measured by Micro-neutralization assay, expressed as GMTs for each cohort	Up to 28 days after second vaccination
Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Specific Serum Neutralising Antibody	SARS-CoV-2 Specific Serum Neutralising Antibody as measured by Micro-neutralization assay, expressed as GMFRs for each cohort	Up to 28 days after second vaccination
Seroconversion Rate of SARS-CoV-2 Specific Serum Neutralising Antibody	Seroconversion Rate is defined as the proportion of participants who achieves a greater than or equal to 4-fold rise in SARS-CoV-2 specific serum neutralising antibody level from baseline	Up to 28 days after second vaccination
Geometric Mean Titer (GMT) of SARS-CoV-2 Surrogate Viral Neutralising Antibody	Measured by enzyme-linked immunosorbent assay (ELISA)	Up to 28 days after second vaccination
Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Surrogate Viral Neutralising Antibody	Measured by enzyme-linked immunosorbent assay (ELISA)	Up to 28 days after second vaccination
Seroconversion Rate of SARS-CoV-2 Surrogate Viral Neutralising Antibody	Seroconversion Rate is defined as a greater than or equal to 4-fold rise in SARS-CoV-2 surrogate viral neutralising antibody from baseline	Up to 28 days after second vaccination
Geometric Mean Titer (GMT) of RBD-specific IgG Antibody	Measured by enzyme-linked immunosorbent assay (ELISA)	Up to 28 days after second vaccination
Geometric Mean Fold Rise (GMFR) of RBD-specific IgG Antibody	Measured by enzyme-linked immunosorbent assay (ELISA)	Up to 28 days after second vaccination
Seroconversion Rate of RBD-specific IgG Antibody	Measured by enzyme-linked immunosorbent assay (ELISA). Seroconversion Rate is defined as a greater than or equal to 4-fold rise in RBD-specific IgG Antibody from baseline	Up to 28 days after second vaccination
Percentage of participants who have positive RBD-specific CD4+ and CD8+ T-cell IFN-y ELISpot responses	Measured by IFN-y ELISpot assay	Up to 28 days after second vaccination
Median number of spot-forming cells (SFC) per 1 million PBMCs	Measured by IFN-y ELISpot assay	Up to 28 days after second vaccination
Percentage of participants who shows positive specific T-helper 1 responses, or T-helper 2 responses	Quantified by Intracellular Cytokine Staining	Up to 28 days after second vaccination
Medium percentage of specific T-helper 1 responses or T-helper 2 responses	Quantified by Intracellular Cytokine Staining	Up to 28 days after second vaccination

Collaborators and Investigators

• Sponsor: Baiya Phytopharm Co., Ltd.
• Collaborators: National Vaccine Institute, Thailand

Study record dates

Study Major Dates

• Study Start (Actual): September 11, 2021
• Primary Completion (Actual): December 2, 2021
• Study Completion (Actual): November 4, 2022

Study Registration Dates

• First Submitted: June 14, 2021
• First Submitted That Met QC Criteria: July 6, 2021
• First Posted (Actual): July 7, 2021

Study Record Updates

• Last Update Posted (Actual): January 12, 2023
• Last Update Submitted That Met QC Criteria: January 11, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: SARS-CoV-2; COVID-19; SARS-CoV-2 Vaccine; COVID-19 Vaccine
• Additional Relevant MeSH Terms: Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Coronavirus Infections
• Other Study ID Numbers: PT-CR-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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