The purpose of this research study is to evaluate the safety of and the body's immune response to single and multiple vaccinations in healthy men and women. We want to find out what effects GBP511 has on you and your health. We are doing this study to find out: If the study drug has any side effects when given as single and multiple vaccinations. If reactogenicity, an indication that the immune systems is working and is preparing to protect the body against future infection, occurs. This is a normal physical inflammatory response that occurs after vaccination, manifesting as localised reactions that may include pain or redness at the injection site, or systemic symptoms such as headache or fever. If immunogenicity which is when GBP511 causes your body to make antibodies against the non-harmful viral proteins contained within GBP511, called 'neutralising antibodies (Nab),' occurs. And if GBP511 will cause the specialised cells of the body's immune system to mount a defence against the non-harmful viral proteins contained within GBP511, called 'cell-mediated immunity (CMI)'. In this study, GBP511 will be administered with and without adjuvant, CAS-1. An adjuvant is an ingredient used in some vaccines that help produce a stronger immune response in the people receiving the vaccine and thus helps the vaccine work better. This study will recruit approximately 368 participants in total and will be conducted in two stages: Stage 1 will look at two vaccinations with GBP511 when given with and without the CAS-1 adjuvant; and Stage 2 will look at either one or two vaccinations with two candidate GBP511 vaccines chosen from Stage 1 of the study. Participants will be required to attend Linear's clinical unit on two separate occasions to receive their two vaccinations. On the first day of dosing (Visit 2/Day 1) and second day of dosing (Visit 5/Day 29), we will be testing a single dose of the study drug in up to 168 healthy volunteers who will be divided into 3 groups. Group 1, Groups 2 and 3 will have 56 people each. These 3 groups will be divided into treatment subgroups, with a total of 6 test subgroups and 3 control subgroups. In all groups, neither you or the study doctor will know what subgroup you are part of, and therefore what treatment (GBP511 or Comirnaty+ placebo) you will receive.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
368
injection volume of 0.5mililiter (mL) with 2-doses at 4 weeks interval in stage 1 and 1-dose or 2-doses at 4 weeks interval in stage 2. Low dose: 2μg/strain, Mid dose: 6μg/strain, High dose: 18μg/strain
injection volume of 0.5mililiter (mL) with 2-doses at 4 weeks interval in stage 1 and 1-dose or 2-doses at 4 weeks interval in stage 2. Low dose: 2μg/strain, Mid dose: 6μg/strain, High dose: 18μg/strain
injection volume of 0.5mililiter (mL) with 2-doses at 4 weeks interval in stage 1 and 1-dose or 2-doses at 4 weeks interval in stage 2. Low dose: 2μg/strain, Mid dose: 6μg/strain, High dose: 18μg/strain
injection volume of 0.5mililiter (mL) with 2-doses at 4 weeks interval in stage 1 and 1-dose or 2-doses at 4 weeks interval in stage 2. GBP511 - Low dose: 2μg/strain, Mid dose: 6μg/strain, High dose: 18μg/strain CAS-1 standard adjuvant dose
injection volume of 0.5mililiter (mL) with 2-doses at 4 weeks interval in stage 1 and 1-dose or 2-doses at 4 weeks interval in stage 2. GBP511 - Low dose: 2μg/strain, Mid dose: 6μg/strain, High dose: 18μg/strain CAS-1 standard adjuvant dose
injection volume of 0.5mililiter (mL) with 2-doses at 4 weeks interval in stage 1 and 1-dose or 2-doses at 4 weeks interval in stage 2. GBP511 - Low dose: 2μg/strain, Mid dose: 6μg/strain, High dose: 18μg/strain CAS-1 standard adjuvant dose
injection volume of 0.3mililiter (mL) with single-dose at visit 2. 30 mcg of SARS-CoV-2 LP.8.1 spike protein mRNA per 0.3mL
injection volume of 0.5mililiter (mL) with single-dose at visit 5.
Participants will receive 2 intramuscular injections of the test vaccine in stage 2. Injections on Day 1, 29 (Visit 2, 5), in line with the selected dose regimen in stage 1.
Participants will receive 2 intramuscular injections of the test vaccine in stage 2. Injections on Day 1, 29 (Visit 2, 5), in line with the selected dose regimen in stage 1.
Momentum Clinical Research Darlinghurst
Sydney, Kent Street, Australia
Linear
Joondalup, Western Australia, Australia
Linear
Nedlands, Western Australia, Australia
Percentage of participants experiencing any immediate reactions
For stage 1
Time frame: 30 minutes (2 hours for sentinel participants) following each study vaccination
Percentage of participants reporting any solicited local AEs
For stage 1
Time frame: during the 7 days following each study vaccination
Percentage of participants reporting any solicited systemic AEs
For stage 1
Time frame: during the 7 days following each study vaccination
Percentage of participants experiencing any unsolicited AEs
For stage 1
Time frame: during the 28 days following each study vaccination
Percentage of participants experiencing any SAEs, MAAEs, AESIs, as well as AE leading to study withdrawal
For stage 1
Time frame: 1st Vaccination date, 1 week, 2 weeks, 4 weeks following the 1st study vaccination, and 2nd vaccination date, 1 week, 2 weeks, 4 weeks, 3 months, 6 months, and 12 months following the 2nd study vaccination.
GMT of neutralizing antibody against each matched strain measured by a pseudo-virus neutralization assay at each time point.
For stage 2
Time frame: At baseline, 2 weeks, 4 weeks following the 1st study vaccination, and 2 weeks, 4 weeks, 3 months, 6 months, and 12 months following the last study vaccination.
GMR of neutralizing antibody against each matched strain measured by a pseudo-virus neutralization assay, from each pre-vaccination to subsequent time point.
For stage 2
Time frame: At baseline, 2 weeks, 4 weeks following the 1st study vaccination, and 2 weeks, 4 weeks, 3 months, 6 months, and 12 months following the last study vaccination.
Percentage of participants with ≥ 2-fold and 4-fold rises against each matched strain in pseudo-virus neutralizing antibody titer, from baseline to each subsequent time point
For stage 2
Time frame: At baseline, 2 weeks, 4 weeks following the 1st study vaccination, and 2 weeks, 4 weeks, 3 months, 6 months, and 12 months following the last study vaccination.
Geometric mean titer (GMT) of neutralizing antibody against each matched strain measured by a pseudo-virus neutralization assay
For stage 1
Time frame: At baseline, 2 weeks, 4 weeks following the 1st study vaccination, and 2 weeks, 4 weeks, 3 months, 6 months, and 12 months following the 2nd study vaccination.
Geometric mean ratio (GMR) of neutralizing antibody against each matched strain measured by a pseudo-virus neutralization assay
For stage 1
Time frame: From pre-vaccination to baseline, 2 weeks, 4 weeks following the 1st study vaccination, and 2 weeks, 4 weeks, 3 months, 6 months, and 12 months following the 2nd study vaccination.
Percentage of participants with ≥ 2-fold and 4-fold rises against each matched strain in pseudo-virus neutralizing antibody titer
For stage 1
Time frame: At baseline, 2 weeks, 4 weeks following the 1st study vaccination, and 2 weeks, 4 weeks, 3 months, 6 months, and 12 months following the 2nd study vaccination.
GMT of RBD-binding IgG antibody against each matched strain measured by ECL assay at each time point.
For stage 1,2
Time frame: At baseline, 2 weeks, 4 weeks following the 1st study vaccination, and 2 weeks, 4 weeks, 3 months, 6 months, and 12 months following the 2nd study vaccination (following the last vaccination for stage 2)
GMR of RBD-binding IgG antibody against each matched strain measured by ECL assay, from each pre-vaccination to subsequent time point.
For stage 1,2
Time frame: At baseline, 2 weeks, 4 weeks following the 1st study vaccination, and 2 weeks, 4 weeks, 3 months, 6 months, and 12 months following the 2nd study vaccination(following the last vaccination for stage 2).
Percentage of participants with ≥ 2-fold and 4-fold rises in RBD-binding IgG titer against each matched strain, measured by ECL assay, from baseline to each subsequent time point.
For stage 1,2
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Time frame: At baseline, 2 weeks, 4 weeks following the 1st study vaccination, and 2 weeks, 4 weeks, 3 months, 6 months, and 12 months following the 2nd study vaccination(following the last vaccination for stage 2).
GMT of neutralizing antibody against each mismatched strain measured by a pseudo-virus neutralization assay at each time point.
For Stage 1, The endpoints will be evaluated exclusively in a subset of approximately 33% of participants at the following time points: baseline, 2 weeks, 4 weeks following the 1st study vaccination, and 2 weeks, 4 weeks, 3 months, 6 months, and 12 months following the 2nd study vaccination. For Stage 2, The endpoints will be evaluated exclusively in a subset of approximately 20% of participants at the following time points: baseline, 2 weeks, 4 weeks following the 1st study vaccination, and 2 weeks, 4 weeks, 3 months, 6 months, and 12 months following the last study vaccination.
Time frame: baseline, 2 weeks, 4 weeks following the 1st study vaccination, and 2 weeks, 4 weeks, 3 months, 6 months, and 12 months following the 2nd study vaccination (following the last vaccination for stage 2).
GMR of neutralizing antibody against each mismatched strain measured by a pseudo-virus neutralization assay, from each pre-vaccination to subsequent time point.
For Stage 1, The endpoints will be evaluated exclusively in a subset of approximately 33% of participants at the following time points: baseline, 2 weeks, 4 weeks following the 1st study vaccination, and 2 weeks, 4 weeks, 3 months, 6 months, and 12 months following the 2nd study vaccination. For Stage 2, The endpoints will be evaluated exclusively in a subset of approximately 20% of participants at the following time points: baseline, 2 weeks, 4 weeks following the 1st study vaccination, and 2 weeks, 4 weeks, 3 months, 6 months, and 12 months following the last study vaccination.
Time frame: baseline, 2 weeks, 4 weeks following the 1st study vaccination, and 2 weeks, 4 weeks, 3 months, 6 months, and 12 months following the 2nd study vaccination (following the last vaccination for stage 2).
Percentage of participants with ≥ 2-fold and 4-fold rises against each mismatched strain in pseudo-virus neutralizing antibody titer, from baseline to each subsequent time point.
For Stage 1, The endpoints will be evaluated exclusively in a subset of approximately 33% of participants at the following time points: baseline, 2 weeks, 4 weeks following the 1st study vaccination, and 2 weeks, 4 weeks, 3 months, 6 months, and 12 months following the 2nd study vaccination. For Stage 2, The endpoints will be evaluated exclusively in a subset of approximately 20% of participants at the following time points: baseline, 2 weeks, 4 weeks following the 1st study vaccination, and 2 weeks, 4 weeks, 3 months, 6 months, and 12 months following the last study vaccination.
Time frame: baseline, 2 weeks, 4 weeks following the 1st study vaccination, and 2 weeks, 4 weeks, 3 months, 6 months, and 12 months following the 2nd study vaccination (following the last vaccination for stage 2).
Cell-mediated response for both Th1 and Th2 cytokines (including but not limited to IFN-γ, IL-2, and IL-4 produced by T lymphocytes) measured by FluoroSpot
For Stage 1, The following endpoint will be evaluated exclusively in sentinel participants at the following time points: baseline, 2 weeks following the 1st study vaccination, and 2 weeks, and 6 months following the 2nd study vaccination. For Stage 2, The following endpoints will be evaluated exclusively in a subset of approximately the first 20% of participants at the following time points: baseline, 2 weeks following the 1st study vaccination, and 2 weeks, and 6 months following the last study vaccination.
Time frame: baseline, 2 weeks following the 1st study vaccination, and 2 weeks, and 6 months following the 2nd study vaccination(following the last vaccination for stage 2).
Percentage of participants experiencing any immediate reactions
For stage 2
Time frame: within 30 minutes following each study vaccination
Percentage of participants reporting any solicited local AEs
For stage 2
Time frame: during the 7 days following each study vaccination
Percentage of participants reporting any solicited systemic AEs
For stage 2
Time frame: during the 7 days following each study vaccination
Percentage of participants experiencing any unsolicited AEs
For stage 2
Time frame: during the 28 days following each study vaccination
Percentage of participants experiencing any SAEs, MAAEs, AESIs, as well as AE leading to study withdrawal
For stage 2
Time frame: during the entire study period