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COVID-19 PandemicPhase 2SH-MO-214NCT05383560

Safety and Immunogenicity of Omicron Variant-Matched Vaccine Booster in Adults

A Phase 2 study testing mRNA-1273.214 Vaccine, MRNA-1273 Vaccine and MRNA-1273.222 Vaccine in people with COVID-19 Pandemic and Immunogenicity, run by Sheba Medical Center at 1 site in Israel.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 21 years and olderHealthy volunteers can take part
What is being tested?
mRNA-1273.214 Vaccine, MRNA-1273 Vaccine and MRNA-1273.222 Vaccine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
179 participants
Where
1 siteIsrael
Study dates
5 Sep 2022to 31 Jan 2024
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 21 years and older
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Male or female participants 21 years of age, inclusively.
  • Protocol versions 1.01-1.06:Individuals who previously received mRNA primary series vaccination AND a booster dose at least 4 months prior to Day 1. Documented confirmation of prior mRNA series vaccination receipt must be obtained prior to randomization. Protocol version 1.07:Individuals who had previously received mRNA primary series vaccination comprising at least 3 vaccine doses with the last one at least 6 months prior to Day 1. Documented confirmation of prior mRNA series vaccination receipt must be obtained prior to randomization. Note: subjects who had received 4 vaccine doses (i.e., a primary series of 3 doses and an additional boost) may also be enrolled under protocol version 1.07).
  • Females and males of childbearing potential must be willing to use effective methods of contraception such as hormones (OCP, oral contraceptive pill), condom or occlusive cap with spermicidal agents, intrauterine device (IUD), or intrauterine system (IUS) as well as to refrain from donating sperm through 28 days following the last vaccination.
  • Participant who is willing and able to comply with all scheduled visits, vaccination plan, laboratory tests, lifestyle considerations, and other study procedures.
  • For Women of Child Bearing Potential (WOCBP): a negative pregnancy test on the day of vaccination (Visit 1 and Visit 4).
  • Participant who is willing and able to operate an electronic diary.
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  • 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.
  • Note: Healthy participants with preexisting stable disease, defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the six (6) weeks before enrollment, can be included.
  • Capable of giving signed informed consent as described which includes understanding and compliance with the study procedures, requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
  • Must agree not to enroll in another study of an investigational agent prior to completion of the study.

Who cannot join

  • History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (e.g., anaphylaxis) to any component of the study intervention(s).
  • 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 or positive antigen test for SARS-CoV-2 at baseline.
  • Immunocompromised individuals with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination.
  • Has known or suspected allergy or history of anaphylaxis, urticaria, or other significant AR to the vaccine or its excipients.
  • Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection.
  • Inability to observe possible local reactions at the injection sites due to a physical condition or permanent body art.
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  • Any medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
  • Pregnant or breastfeeding women.
  • Individuals who receive treatment with radiotherapy or immunosuppressive therapy, including cytotoxic agents or systemic corticosteroids (if systemic corticosteroids are administered for ≥14 days at a dose of ≥20 mg/day of prednisone or equivalent), e.g., for cancer or an autoimmune disease, or planned receipt throughout the study. Inhaled/nebulized, intra-articular, intrabursal, or topical (skin or eyes) corticosteroids are permitted.
  • Receipt of blood/plasma products, immunoglobulin, or monoclonal antibodies, from 60 days before study intervention administration, or receipt of any passive antibody therapy specific to COVID-19, from 90 days before study intervention administration, or planned receipt throughout the study.
  • Participation in other studies involving study intervention within 28 days prior to study entry through and including 28 days after the last dose of study intervention.

Trial locations and contacts

1 site in 1 country.

Israel1 site

  • Sheba Medical Center

    Ramat Gan, 5265601

Other trials in Israel

About this study

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

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.

Read the 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).

Being tested
mRNA-1273.214 Vaccine, MRNA-1273 Vaccine, Placebo, MRNA-1273.222 Vaccine
Keywords
mRNA1273.214, Omicron, Immunogenicity, COVID-19, Safety, mRNA1273.222
Medical subject headings
COVID-19

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • mRNA-1273.214 VaccineBiological

    Omicron Variant-Matched Vaccine

  • MRNA-1273 VaccineBiological

    Also called Spikevax

    Moderna's commercial COVID-19 Vaccine

  • PlaceboBiological

    Normal Saline for injection

  • MRNA-1273.222 VaccineBiological

    Also called Spikevax Bivalent

    Moderna's commercial COVID-19 Vaccine

Study groups in NCT05383560
Study groupRoleWhat they receive
mRNA-1273.214 + mRNA-1273.214ExperimentalFourth \& Fifth doses of an investigational mRNA vaccine, 56 days apart N ≈ 60 Under protocol versions 1.01-1.06
Receives: Biological: mRNA-1273.214 Vaccine
mRNA-1273.214 + PlaceboExperimentalFourth dose of an investigational mRNA vaccine followed by a fifth dose of placebo, 56 days apart N ≈ 60 Under protocol versions 1.01-1.06
Receives: Biological: mRNA-1273.214 Vaccine; Biological: Placebo
mRNA-1273 + PlaceboActive comparatorFourth dose of the commercial mRNA vaccine, followed by a fifth dose of placebo, 56 days apart N ≈ 30 Under protocol versions 1.01-1.06
Receives: Biological: MRNA-1273 Vaccine; Biological: Placebo
mRNA-1273.214ExperimentalA booster dose of an investigational mRNA vaccine at Visit 1 (Day 1). N ≈ 30 Under protocol versions 1.07
Receives: Biological: mRNA-1273.214 Vaccine
mRNA-1273.222Active comparatorA booster dose of the commercial mRNA vaccine at Visit 1 (Day 1). N ≈ 30 Under protocol versions 1.07
Receives: Biological: MRNA-1273.222 Vaccine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety of the study vaccines after each dose

    Safety of the study vaccines will be measured by solicited and unsolicited adverse injection site reactions and systemic reactions from the time of each vaccination through 7 days post each vaccination/placebo administrations. AEs will be collected up to 29 days after injection. Unsolicited non-serious AEs, SAEs, NOCMCs, and MAAEs will be collected through 6 months after the first vaccine dose.

    Measured: 6 Months

  2. Reactogenicity of the study vaccines after each dose

    Reactogenicity of the study vaccines will be measured by solicited and unsolicited adverse injection site reactions and systemic reactions from the time of each vaccination through 7 days post each vaccination/placebo administrations. AEs will be collected up to 29 days after injection. Unsolicited non-serious AEs, SAEs, NOCMCs, and MAAEs will be collected through 6 months after the first vaccine dose. The study will also assess reactogenicity using "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials" Guide, via an electronic diary the participants would be required to complete every day for 7 consecutive days starting the day of each vaccine.

    Measured: 6 Months

  3. Immune response to mRNA-1273.214, given as a fourth and fifth dose to participants who previously received mRNA primary series vaccination and one booster dose (third dose).

    Primary immunogenicity outcome will be measured by changes in geometric titers (GMTs) and geometric fold raise (GMFRs) of IgG and neutralizing antibodies (nAb), using a pseudovirus assay during all visits. Blood for immunogenicity will be collected at all visits (total of 6 visits).

    Measured: 6 Months

Secondary outcomes (2)

  1. Immunogenicity

    Describe direct virus neutralization of Omicron VOC, Delta VOC and ancestral SARS-COV-2 VOC. Direct virus neutralization (in Biosafety Level 3 - BL3 - facility) of Omicron variant of concern (VOC) and two (2) additional strains [ancestral SARS-COV-2 and Delta VOC] Measured by GMT.

    Measured: 6 Months

  2. Investigational Product's Efficacy

    COVID-19 infections and severity [based on CDC definition] in participants without evidence of past SARS-CoV-2 infection, occurring after day 7 from the booster dose throughout the blinded follow-up period. Laboratory defined SARS-CoV-2 infection and symptomatic COVID-19 and severe COVID-19.

    Measured: 6 Months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 May 2022
  2. Study start5 Sep 2022
  3. Primary completion31 Jan 2024
  4. Study completion31 Jan 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Sequential
Model description
Protocol versions 1.01-1.06:Randomized, Observer-Blinded (2:2:1 ratio) Protocol version 1.07:Randomized, Observer-Blinded (1:1 ratio)
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
179 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05383560
Sponsor's protocol ID
Sheba-22-9312
Acronym
SH-MO-214
Status last verified
Feb 2024
First submitted
15 May 2022
Last updated
21 Feb 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Unidentified data will be available after publication of the results.

Publications

  • Lustig Y, Barda N, Weiss-Ottolenghi Y, Indenbaum V, Margalit I, Asraf K, Doolman R, Chalkias S, Das R, Elfatarany G, Harats D, Kreiss Y, Regev-Yochay G. Humoral response superiority of the monovalent XBB.1.5 over the bivalent BA.1 and BA.5 mRNA COVID-19 vaccines. Vaccine. 2024 Sep 17;42(22):126010. doi: 10.1016/j.vaccine.2024.05.058. Epub 2024 May 27.

    PubMed 38806352

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing mRNA-1273.214 Vaccine, MRNA-1273 Vaccine and MRNA-1273.222 Vaccine in people with COVID-19 Pandemic and Immunogenicity, run by Sheba Medical Center at 1 site in Israel.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety of the study vaccines after each dose (time frame: 6 Months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05383560, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Feb 2024.

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