Ignite Creation Date:
2025-12-25 @ 2:16 AM
Ignite Modification Date:
2025-12-27 @ 2:06 PM
Study NCT ID:
NCT05383560
Status:
COMPLETED
Last Update Posted:
2024-02-21
First Post:
2022-05-15
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Safety and Immunogenicity of Omicron Variant-Matched Vaccine Booster in Adults
Sponsor:
Sheba Medical Center
Organization:
Study Overview
Official Title:
Phase 2, Randomized, Observer-Blind, Investigator-Initiated, Collaborative Study to Evaluate the Safety and Immunogenicity of Omicron Variant-Matched Vaccine Booster in Adults
Status:
COMPLETED
Status Verified Date:
2024-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
SH-MO-214
Brief Summary:
Under protocol versions 1.01-1.06: The five recently emerged SARS-CoV2 variants that were designated as VOCs are the Alpha variant, Beta variant, Gamma variant, Delta variant and the Omicron variant. The current dominant Omicron variant was designated a VOC by WHO on Nov 26, 2021, and was found to comprise 85% of reported variants in late January 2022. Studies have shown that the prevalent Omicron mutations in the S1 subunit RBD region and NTD region could dramatically change the antigenic features of the viral spike, leading to significantly reduced neutralization Omicron harbors 30 signature mutations (\>50% prevalence) of which 15 are in the S1 subunit RBD region and 8 are in the S1 subunit NTD region. Omicron is a highly contagious variant with threatening immune evasion capabilities even despite robust immune response. Initial modeling showed the Omicron variant being 2.8 times more infectious than the Delta variant. While current vaccines are losing protection against Omicron with respect to infection and mild disease, there is still considerable protection from hospitalisation and severe COVID-19, especially after a booster dose. The International Coalition of Medicines Regulatory Authorities (ICMRA) COVID-19 Omicron Variant Workshop encouraged the international scientific community and vaccine developers to look at alternative approaches to monovalent vaccines. In ICMRA's view, companies should also explore the feasibility of developing bivalent or multivalent variant vaccines to determine if they offer advantages to monovalent vaccines. As advised by ICMRA, the investigated vaccine, mRNA-1273.214 is a bivalent vaccine containing the ancestral SARS-CoV-2 and the Omicron variant spike sequences that will be evaluated as a heterologous boost.
Under protocol version 1.07:The study will also investigate the safety, reactogenicity and immune response of the mRNA-1273.222 administered as a boost vaccine after primary series vaccination comprising 3 doses of an mRNA vaccine .
This study hypothesizes that the peak level of antibodies against SARS CoV-2, will be at two weeks after the first study dose is administered, which is similar to other recent findings (Anderson et al., 2022).2.2.1. The bivalent mRNA-1273.222 vaccine contains mRNA encoding for the spike protein of BA.4/BA.5 as well as mRNA encoding for the original (ancestral Wuhan-Hu-1) strain of the SARS-CoV-2 virus.
Under protocol version 1.07:The study will also investigate the safety, reactogenicity and immune response of the mRNA-1273.222 administered as a boost vaccine after primary series vaccination comprising 3 doses of an mRNA vaccine .
This study hypothesizes that the peak level of antibodies against SARS CoV-2, will be at two weeks after the first study dose is administered, which is similar to other recent findings (Anderson et al., 2022).2.2.1. The bivalent mRNA-1273.222 vaccine contains mRNA encoding for the spike protein of BA.4/BA.5 as well as mRNA encoding for the original (ancestral Wuhan-Hu-1) strain of the SARS-CoV-2 virus.
Detailed Description:
Under protocol versions 1.01-1.06:The trial aims to evaluate the safety and immunogenicity of the investigated covalent vaccine, mRNA-1273.214, administered as a heterologous vaccine after the primary series vaccination and boost with the BNT162b2 or mRNA-1273, in healthy adults aged ≥21 years.
Three different treatment arms will be compared with participants being administered either:
1. mRNA-1273.214 (Day 1) and mRNA-1273.214 (Day 56)
2. mRNA-1273.214 (Day 1) and placebo (Day 56)
3. mRNA-1273 (Day 1) and placebo (Day 56)
Study procedures include two administrations of vaccine and/or placebo, nasopharyngeal swab for SARS-CoV-2 PCR, blood draws for antibody response: IgG, IgA, pseudo-neutralization antibody (ab) titers, B-Cell response, T-Cell response, and solicited and non-solicited adverse events. Subjects will be asked to complete an electronic diary for 7 consecutive days after each vaccination dose, regarding vaccine-related symptoms + temperature measured at home. One week after the day of vaccination or placebo, subjects will be asked to complete a COVID-19 questionnaire once a week, in which they will have to answer the question of whether they have experienced COVID-19 symptoms. Adverse reactions will be measured by the occurrence of solicited injection site reaction and systemic reaction from the time of each vaccination through 7 days post each vaccination/placebo administration. Unsolicited non-serious Adverse Events (AEs), Serious adverse events (SAEs), new-onset chronic medical conditions (NOCMCs), and medically-attended adverse events (MAAEs) will be collected from baseline through 6 months after the first booster dose vaccination.
Nasopharyngeal Swab for SARS-CoV-2 PCR, Blood Samples For Immunogenicity Assessment, Serology and PBMC will be collected at each study visit (6 times during the subject's participation in the study).
Under protocol version 1.07:The trial aims is to evaluate the safety and immunogenicity of the messenger-RNA (mRNA) based bivalent vaccine candidates mRNA-1273.214 and mRNA-1273.222 administered as second and/or third boosts to healthy adults aged ≥25 years who received at least a primary series of 3 doses of mRNA vaccination. The total study population will include 180 subjects.
The study will include two (2) additional arms. At Visit 1 (Day 1), subjects will be administered a booster dose of mRNA-1273.222 vaccine (arm 4), or mRNA-1273.214 vaccine (arm 5). Up to 60 subjects will be enrolled for arms 4 and 5 (\~30 subjects per arm).
Note: all subjects enrolled under protocol versions 1.01-1.06 (arms 1-3) will continue with their planned procedures as described in protocol version 1.06.
Subjects enrolled under protocol version 1.07 (arms 4 and 5), will participate in five (5) visits:
Visit 1 (Day 1) Visit 2 (Day 15 ± 3 days) Visit 3 (Day 29 + 12 days) Visit 4 (Day 91 ± 7 days) Visit 5 (Day 181 ± 14 days) The injection with the investigated vaccine booster mRNA-1273.214 (Arm 4) or mRNA-1273.222 (Arm 5) will be given at Visit 1.
Unblinding for subjects enrolled under protocol version 1.07 will be performed at Visit 4 (Day 91 ± 7 days).
Three different treatment arms will be compared with participants being administered either:
1. mRNA-1273.214 (Day 1) and mRNA-1273.214 (Day 56)
2. mRNA-1273.214 (Day 1) and placebo (Day 56)
3. mRNA-1273 (Day 1) and placebo (Day 56)
Study procedures include two administrations of vaccine and/or placebo, nasopharyngeal swab for SARS-CoV-2 PCR, blood draws for antibody response: IgG, IgA, pseudo-neutralization antibody (ab) titers, B-Cell response, T-Cell response, and solicited and non-solicited adverse events. Subjects will be asked to complete an electronic diary for 7 consecutive days after each vaccination dose, regarding vaccine-related symptoms + temperature measured at home. One week after the day of vaccination or placebo, subjects will be asked to complete a COVID-19 questionnaire once a week, in which they will have to answer the question of whether they have experienced COVID-19 symptoms. Adverse reactions will be measured by the occurrence of solicited injection site reaction and systemic reaction from the time of each vaccination through 7 days post each vaccination/placebo administration. Unsolicited non-serious Adverse Events (AEs), Serious adverse events (SAEs), new-onset chronic medical conditions (NOCMCs), and medically-attended adverse events (MAAEs) will be collected from baseline through 6 months after the first booster dose vaccination.
Nasopharyngeal Swab for SARS-CoV-2 PCR, Blood Samples For Immunogenicity Assessment, Serology and PBMC will be collected at each study visit (6 times during the subject's participation in the study).
Under protocol version 1.07:The trial aims is to evaluate the safety and immunogenicity of the messenger-RNA (mRNA) based bivalent vaccine candidates mRNA-1273.214 and mRNA-1273.222 administered as second and/or third boosts to healthy adults aged ≥25 years who received at least a primary series of 3 doses of mRNA vaccination. The total study population will include 180 subjects.
The study will include two (2) additional arms. At Visit 1 (Day 1), subjects will be administered a booster dose of mRNA-1273.222 vaccine (arm 4), or mRNA-1273.214 vaccine (arm 5). Up to 60 subjects will be enrolled for arms 4 and 5 (\~30 subjects per arm).
Note: all subjects enrolled under protocol versions 1.01-1.06 (arms 1-3) will continue with their planned procedures as described in protocol version 1.06.
Subjects enrolled under protocol version 1.07 (arms 4 and 5), will participate in five (5) visits:
Visit 1 (Day 1) Visit 2 (Day 15 ± 3 days) Visit 3 (Day 29 + 12 days) Visit 4 (Day 91 ± 7 days) Visit 5 (Day 181 ± 14 days) The injection with the investigated vaccine booster mRNA-1273.214 (Arm 4) or mRNA-1273.222 (Arm 5) will be given at Visit 1.
Unblinding for subjects enrolled under protocol version 1.07 will be performed at Visit 4 (Day 91 ± 7 days).
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: