COVID-19 PandemicPhase 4NCT05231005
Fourth BNT162b2 COVID-19 Vaccine Dose
A Phase 4 study testing BNT162b2 vaccine in people with COVID-19 Pandemic, run by Sheba Medical Center at 1 site in Israel.
Trial summary
The Omicron variant of concern (VOC) is currently rapidly spreading worldwide, with extremely high transmission rates, with an estimated R of >3. the investigators now have preliminary, yet unpublished data, showing slow waning of the immune response after the third dose of the BNT162b2 mRNA vaccine within 4 months… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- COVID-19 Pandemic
- What is being tested?
- BNT162b2 vaccine
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,000 participants
- Where
- 1 siteIsrael
- Study dates
- 27 Dec 2021to 26 Jun 2024
- Phase
- Phase 4
- 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 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age: Volunteer must be at least 18 years of age, at the time of signing the informed conset.
- Sex: Male or Female. All female volunteers of reproductive age will be requested to use contraceptive measures for the two months following enrolment.
- Received 3 doses of BNT162b2 with the 3rd dose at least 4 months previously.
- Have a serology test within the previous 3 months of 700 BAU or less.
- Responded to the previous vaccine doses, i.e. at least one IgG>100.
- Medical Conditions: Volunteers with any medical condition are allowed, as long as they adhere to the criteria above.
- Agreed to attend all visits and signed the informed consent -
Who cannot join
- 1. Had previous SARS-CoV-2 infection (detected by either PCR, anti-S IgG before the 1st vaccine dose, anti-N IgG at any stage).
- 2. Had an allergic response to any of the previous BNT162b2 doses. 3. Has history of myopericarditis. 4. Report that they do not feel well or have a fever on the day of vaccination. 5. Pregnant on day of recruitment.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Fourth BNT162b2 COVID-19 Vaccine Dose - the Sheba HCW Cohort
The Omicron variant of concern (VOC) is currently rapidly spreading worldwide, with extremely high transmission rates, with an estimated R of >3.
the investigators now have preliminary, yet unpublished data, showing slow waning of the immune response after the third dose of the BNT162b2 mRNA vaccine within 4 months after this dose . While these data would not have been worrisome in the Delta VOC era, this may be different with the emergence of the Omicron VOC.
Read more
These data raise the question of when and will a 4th dose be needed to cope with the emergence of Omicron. However, if a have reached the maximal effect of the current vaccine has been reached against Omicron, with a third dose, will a 4th dose have any added value?
Here, the investigators will study the potential immunogenicity of a 4th dose, together with assessing safety and effectiveness in preventing infections
Read the detailed description
The aim of the study is to assess the immunogenicity of a 4th dose, and its durability. This will be measured by following IgG, IgA, Pseudoneutralization assays, microneutralization, avidity, T-cell activity and B-cell repertoire and comparing them to a matched control group, who are participating in the Sheba COVID Cohort study. The investigators will also assess safety and vaccine effectiveness by active surveillance of adverse events and by following incidence of SARS-CoV-2 infections.
This is a prospective intervention study, to test the effect of a 4th dose, by comparing the immune response before and after the 4th dose, given to 150-200 volunteers, as well as comparing their responses with a control group of individuals vaccinated with 3 doses but without the 4th. All study participants would be health care workers from Sheba medical Center, who are participating in the Sheba COVID Cohort study and have a serology test from the previous 3 months. Participation in the study will be confidential and will not be disclosed to the worker's direct supervisor. For this study, the investigators will recruit 150-200 volunteers, who received the 3rd dose at least 4 months previously, and have a known serology history (showing an immune response (even if just a low response) to the three previous doses, but with a recent relatively low IgG (below 700 BAU). Volunteers will tested before and after vaccination with a 4th dose, and followed for 6 months.
As controls, a sub-cohort of similar HCW, who are recruited to the Sheba COVID Cohort study (IRB 8008-20) and are followed monthly with serology tests, and are not receiving the 4th dose. The control group, all of whom signed an informed consent and allowed blood samples to be used for further immunologic studies, will be matched by age, gender, time from 3rd vaccine dose and IgG titers, and will be followed similarly, as by the original 8008-20 protocol.
On recruitment, volunteer will:
- Receive a detailed explanation and sign the informed consent form (appendix ICF)
- Fill an initial inclusion/ exclusion criteria questionnaire.
- Fill a general comorbidity questionnaire (Appendix Q1), additionally they will be screened for COVID-19 symptoms such as fever, cough, anosmia
- Have up to 40cc blood drawn for all serology and cellular immunity tests.
- Perform a PCR for SARS-CoV-2 test
- Receive the 4th dose of BNT162b2 30µg.
- Will have a physician checkup and followup for 15 minutes after receiving the dose.
Six additional visits will follow as described in the research timeline:
- Conditions
- COVID-19 Pandemic
- Being tested
- BNT162b2 vaccine
- Keywords
- COVID-19, BNT162b2 vaccine, Omicron, Immunogenicity
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BNT162b2 vaccineBiological
fourth dose of the BNT162b2 vaccine (30 microgram) adminstered IM
| Study group | Role | What they receive |
|---|---|---|
| 4th dose BNT162b2 vaccine | Experimental | The investigators will recruit 150-200 volunteers, who received the 3rd dose at least 4 months previously, and have a known serology history (showing an immune response (even if just a low response) to the three previous doses, but with a recent relatively low IgG (below 700 BAU). These volunteers will recieve a 4th dose (30 microgram) of the BNT162b2 vaccine Receives: Biological: BNT162b2 vaccine |
| Control | No intervention | As controls, a sub-cohort of similar HCW, who are recruited to the Sheba COVID Cohort study (IRB 8008-20) and are followed monthly with serology tests, and are not receiving the 4th dose. The control group, all of whom signed an informed consent and allowed blood samples to be used for further immunologic studies, will be matched by age, gender, time from 3rd vaccine dose and IgG titers, and will be followed similarly |
What is being measured
The primary outcome is the main question the study is designed to answer.
Geometric mean of antibody titers of each arm, on each time point
Serology tests including IgG, neutralization, Tcell activity . These will be compared between pre- and post- 4th dose as well as with those outcomes in the control group.
Adverse event reporting of vaccinated individuals by an electronic survey that will be filled from visit 2.
Serious adverse events will be defined as any adverse event that resulted in death, hospitalization, permanent damage, required treatment in the emergency room or was life threatening.
Measured: 6 months
Solicited and unsolicited adverse events
Solicited adverse event, including local and systemic as reported in questionnaires and telephone calls on days 5, 7., 14, and 21. Unsolicited AE during the whole study period
Measured: 6 months
Secondary outcomes (1)
Cumulative incidents of infections in each arm
T-cell activity and B-cell repertoire as described below. SARS-CoV-2 incidence and specifically Omicron VOC incidence.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Feb 2022
- Study start27 Dec 2021
- Primary completion26 Jun 2024 (estimated)
- Study completion26 Jun 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for COVID-19 PandemicStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 4
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- This is a prospective intervention study, to test the effect of a 4th dose, by comparing the immune response before and after the 4th dose, given to 150-200 volunteers, as well as comparing their responses with a control group of individuals vaccinated with 3 doses but without the 4th
- Masking
- None (open label)
- Enrolment
- 1,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sheba Medical Center
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Gili Regev-Yochay MD, Sheba Medical Center
- Investigators
- Gili Regev-Yochay, MD, Principal investigator, Sheba Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05231005
- Sponsor's protocol ID
- 8980-21
- Status last verified
- Dec 2023
- First submitted
- 9 Jan 2022
- Last updated
- 27 Dec 2023
- 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 (all IPD that underlie results in a publication)
Publications
Canetti M, Barda N, Gilboa M, Indenbaum V, Mandelboim M, Gonen T, Asraf K, Weiss-Ottolenghi Y, Amit S, Doolman R, Mendelson E, Harats D, Freedman LS, Kreiss Y, Lustig Y, Regev-Yochay G. Immunogenicity and efficacy of fourth BNT162b2 and mRNA1273 COVID-19 vaccine doses; three months follow-up. Nat Commun. 2022 Dec 13;13(1):7711. doi: 10.1038/s41467-022-35480-2.
PubMed 36513665
Study at a glance
From the registry record, last updated by the sponsor on 27 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Fourth BNT162b2 COVID-19 Vaccine Dose - the Sheba HCW Cohort
- ClinicalTrials.gov ID
- NCT05231005
- Acronym / sponsor ID
- 8980-21
- Conditions
- COVID-19 Pandemic
- Keywords
- COVID-19, BNT162b2 vaccine, Omicron, Immunogenicity
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 1,000 participants (estimated)
- Lead sponsor
- Sheba Medical CenterOther government
- Study start
- 27 Dec 2021 (actual)
- Primary completion
- 26 Jun 2024 (estimated)
- Study completion
- 26 Jun 2024 (estimated)
- First posted
- 9 Feb 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The Omicron variant of concern (VOC) is currently rapidly spreading worldwide, with extremely high transmission rates, with an estimated R of >3.
the investigators now have preliminary, yet unpublished data, showing slow waning of the immune response after the third dose of the BNT162b2 mRNA vaccine within 4 months after this dose . While these data would not have been worrisome in the Delta VOC era, this may be different with the emergence of the Omicron VOC.
These data raise the question of when and will a 4th dose be needed to cope with the emergence of Omicron. However, if a have reached the maximal effect of the current vaccine has been reached against Omicron, with a third dose, will a 4th dose have any added value?
Here, the investigators will study the potential immunogenicity of a 4th dose, together with assessing safety and effectiveness in preventing infections
Detailed description
The aim of the study is to assess the immunogenicity of a 4th dose, and its durability. This will be measured by following IgG, IgA, Pseudoneutralization assays, microneutralization, avidity, T-cell activity and B-cell repertoire and comparing them to a matched control group, who are participating in the Sheba COVID Cohort study. The investigators will also assess safety and vaccine effectiveness by active surveillance of adverse events and by following incidence of SARS-CoV-2 infections.
This is a prospective intervention study, to test the effect of a 4th dose, by comparing the immune response before and after the 4th dose, given to 150-200 volunteers, as well as comparing their responses with a control group of individuals vaccinated with 3 doses but without the 4th. All study participants would be health care workers from Sheba medical Center, who are participating in the Sheba COVID Cohort study and have a serology test from the previous 3 months. Participation in the study will be confidential and will not be disclosed to the worker's direct supervisor. For this study, the investigators will recruit 150-200 volunteers, who received the 3rd dose at least 4 months previously, and have a known serology history (showing an immune response (even if just a low response) to the three previous doses, but with a recent relatively low IgG (below 700 BAU). Volunteers will tested before and after vaccination with a 4th dose, and followed for 6 months.
As controls, a sub-cohort of similar HCW, who are recruited to the Sheba COVID Cohort study (IRB 8008-20) and are followed monthly with serology tests, and are not receiving the 4th dose. The control group, all of whom signed an informed consent and allowed blood samples to be used for further immunologic studies, will be matched by age, gender, time from 3rd vaccine dose and IgG titers, and will be followed similarly, as by the original 8008-20 protocol.
On recruitment, volunteer will:
- Receive a detailed explanation and sign the informed consent form (appendix ICF)
- Fill an initial inclusion/ exclusion criteria questionnaire.
- Fill a general comorbidity questionnaire (Appendix Q1), additionally they will be screened for COVID-19 symptoms such as fever, cough, anosmia
- Have up to 40cc blood drawn for all serology and cellular immunity tests.
- Perform a PCR for SARS-CoV-2 test
- Receive the 4th dose of BNT162b2 30µg.
- Will have a physician checkup and followup for 15 minutes after receiving the dose.
Six additional visits will follow as described in the research timeline:
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- This is a prospective intervention study, to test the effect of a 4th dose, by comparing the immune response before and after the 4th dose, given to 150-200 volunteers, as well as comparing their responses with a control group of individuals vaccinated with 3 doses but without the 4th
| Arm | Type | Receives |
|---|---|---|
| 4th dose BNT162b2 vaccine | Experimental | Biological: BNT162b2 vaccineThe investigators will recruit 150-200 volunteers, who received the 3rd dose at least 4 months previously, and have a known serology history (showing an immune response (even if just a low response) to the three previous doses, but with a recent relatively low IgG (below 700 BAU). These volunteers will recieve a 4th dose (30 microgram) of the BNT162b2 vaccine |
| Control | No intervention | –As controls, a sub-cohort of similar HCW, who are recruited to the Sheba COVID Cohort study (IRB 8008-20) and are followed monthly with serology tests, and are not receiving the 4th dose. The control group, all of whom signed an informed consent and allowed blood samples to be used for further immunologic studies, will be matched by age, gender, time from 3rd vaccine dose and IgG titers, and will be followed similarly |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Age: Volunteer must be at least 18 years of age, at the time of signing the informed conset.
- Sex: Male or Female. All female volunteers of reproductive age will be requested to use contraceptive measures for the two months following enrolment.
- Received 3 doses of BNT162b2 with the 3rd dose at least 4 months previously.
- Have a serology test within the previous 3 months of 700 BAU or less.
- Responded to the previous vaccine doses, i.e. at least one IgG>100.
Key exclusion criteria (2 listed)
- 1. Had previous SARS-CoV-2 infection (detected by either PCR, anti-S IgG before the 1st vaccine dose, anti-N IgG at any stage).
- 2. Had an allergic response to any of the previous BNT162b2 doses. 3. Has history of myopericarditis. 4. Report that they do not feel well or have a fever on the day of vaccination. 5. Pregnant on day of recruitment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BNT162b2 vaccinefourth dose of the BNT162b2 vaccine (30 microgram) adminstered IM | Biological | 4th dose BNT162b2 vaccine |
Primary outcome
Geometric mean of antibody titers of each arm, on each time point
Time frame: 6 months
Serology tests including IgG, neutralization, Tcell activity . These will be compared between pre- and post- 4th dose as well as with those outcomes in the control group. Adverse event reporting of vaccinated individuals by an electronic survey that will be filled from visit 2. Serious adverse events will be defined as any adverse event that resulted in death, hospitalization, permanent damage, required treatment in the emergency room or was life threatening.
Solicited and unsolicited adverse events
Time frame: 6 months
Solicited adverse event, including local and systemic as reported in questionnaires and telephone calls on days 5, 7., 14, and 21. Unsolicited AE during the whole study period
1 secondary outcome
Cumulative incidents of infections in each arm
Time frame: 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Dec 2023.
- Derived from this study: PubMed 36513665Canetti M, Barda N, Gilboa M, Indenbaum V, Mandelboim M, Gonen T, Asraf K, Weiss-Ottolenghi Y, Amit S, Doolman R, Mendelson E, Harats D, Freedman LS, Kreiss Y, Lustig Y, Regev-Yochay G. Immunogenicity and efficacy of fourth BNT162b2 and mRNA1273 COVID-19 vaccine doses; three months follow-up. Nat Commun. 2022 Dec 13;13(1):7711. doi: 10.1038/s41467-022-35480-2.
- Individual participant dataSharing planned: Yes. Unidentified data will be available after publication of the results (all IPD that underlie results in a publication)
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gili Regev-Yochay, MD principal investigator
Sheba Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing BNT162b2 vaccine in people with COVID-19 Pandemic, 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 7 inclusion and 2 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: status not confirmed, as of the sponsor's last update on 27 Dec 2023. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
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?
Geometric mean of antibody titers of each arm, on each time point (time frame: 6 months). The study lists 2 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 NCT05231005, 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 27 Dec 2023.