COVID-19Phase 2NCT05736913
Intradermal COVID-19 Vaccination in the Immunocompromised
A Phase 2 study testing ID BNT162b2 vaccine and IM BNT162b2 vaccine in people with COVID-19, run by The University of Hong Kong at 1 site in Hong Kong.
Trial summary
COVID-19 is an infectious disease caused by SARS-CoV-2 virus, causing millions of deaths around the globe since the beginning of the pandemic. COVID-19 vaccination was proven to be effective at reducing both mortality and development of severe COVID-19 after infection. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- COVID-19
- What is being tested?
- ID BNT162b2 vaccine and IM BNT162b2 vaccine
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 130 participants
- Where
- 1 siteHong Kong
- Study dates
- 1 Apr 2021to 30 Jun 2023
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Recruited subjects include adult subjects ≥18 years
- Immunocompromised subjects as defined by the following.
- Patients who have undergone solid organ or stem cell transplantation and on immunosuppressive medication.
- Patients who are on chemotherapy, biologics or other immunosuppressive therapy.
- Patients who are on high-dose corticosteroid (prednisolone 0.5mg/kg daily or equivalent)
- Negative IgG antibody response against Covid19 14 days after the second dose of Covid19 vaccination.
- All subjects have to give written informed consent.
- Subjects must be available to complete the study and comply with study procedures. Willingness to allow for serum samples to be stored beyond the study period, for potential additional future testing to better characterize immune response
Who cannot join
- Inability to comprehend and to follow all required study procedures.
- Have a recent history (documented, confirmed or suspected) of a flu-like disease within a week of vaccination.
- Have a known allergy to polyethylene glycol (PEG) or other components of the study vaccines, or history of any anaphylaxis, serious vaccine reactions, to any excipients.
- Have known active human immunodeficiency virus (HIV) infection.
- Received an experimental agent (vaccine, drug, biologic, device, blood product, or medication) within 1 month prior to vaccination in this study or expect to receive an experimental agent during this study. Unwilling to refuse participation in another clinical study through the end of this study.
- Tympanic temperature ≥ 38°C within 3 days of intended study vaccination
- Have a history of alcohol or drug abuse in the last 5 years.
- Have any condition that the investigator believes may interfere with successful completion of the study
Trial locations and contacts
1 site in 1 country.
Hong Kong1 site, 1 recruiting
- Recruiting
Queen Mary Hospital
Hong Kong, 852
Ivan FN Hung, MD, 22553424, ivanhung@hku.hk
Ricky Zhang, PhD, 22554049, zhangrq@hku.hk
About this study
Official title: Immunogenicity, Safety and Tolerability of Intradermal COVID-19 Vaccination Strategy in Immunocompromised Patients: a Prospective, Randomized Trial.
COVID-19 is an infectious disease caused by SARS-CoV-2 virus, causing millions of deaths around the globe since the beginning of the pandemic. COVID-19 vaccination was proven to be effective at reducing both mortality and development of severe COVID-19 after infection. Vaccine-elicited protection is particularly important for immunocompromised patients, as they are more susceptible to infections with their defective immune response, for instance, previous review had suggested that patients with malignancies and recipients of solid organ transplants may be at increased risk of developing severe COVID-19 disease and even death.
To further complicate the scenario, there are two obstacles: firstly, immunocompromised individuals may have suboptimal response from vaccinations, as studies have shown that recipients of solid organ transplant have suboptimal or even are seronegative after the fourth dose booster vaccination . Secondly, with constant mutation of the SARS-CoV-2 viruses, new variants evolve over time, leading to reduction in vaccine efficacy and breakthrough infection in healthy individuals. Therefore, novel vaccine strategy should be considered to enhance the vaccine response in these immunocompromised individuals.
In this study, intradermal injection instead of intramuscular injection for vaccine delivery is proposed, as the investigators have observed improved immunogenicity and few adverse events from previous experience of influenza vaccination. The study aims to evaluate the immunogenicity, safety and tolerability of intradermal COVID-19 vaccination in immunocompromised patients.
Read the detailed description
This is a randomized controlled trial performed in the Hong Kong West Cluster Hospitals under the Hospital Authority in Hong Kong. Immunocompromised individuals who completed two doses of COVID-19 vaccine are recruited and received a booster dose of BNT162b2 vaccine. Recruited individuals include patients who received solid organ transplant (SOT), patients who received stem cell or bone marrow transplant (SCBOT), patients who are undergoing chemotherapy or immunotherapy (COI) and patients who are receiving biologics therapy (BI). The study was approved by the institutional review board of the University of Hong Kong and Hospital Authority (UW 21-214).
After recruitment, participants are randomized to receive either one 30-μg dose (0.3 mL) of intramuscular BNT162b2 booster dose vaccination or one 30-μg dose (0.3 mL) of intradermal BNT162b2 booster dose vaccination. In addition, participants are further subdivided into different groups based on the priming vaccine received. Participant's blood samples are collected before booster vaccination (baseline), 28 days after booster dose, 3 months after booster dose and 6 months after booster dose vaccination. Blood samples collected are tested with live virus microneutralization assay (vMN), performed in the Biosafety level 3 facility of HKU to determine the level of neutralizing antibody in sera. Serial 2-fold dilutions of serum starting from 1:10 are incubated with 100 median tissue culture infectious doses (TCID50) of ancestral strain SARS-CoV-2, BA.1, BA.5.2, and XBB for 1.5 h at 37 °C. Then, a serum-virus mixture is added to VeroE6/TMPRSS2 cells (JCRB Cell Bank Catalogue no. JCRB1819) on 96-well plates. After 72 h of incubation at 37 °C and 5% CO2, the cytopathic effect (CPE) is examined and the antibody titre is determined by the highest dilution with 50% inhibition of CPE. In addition, A Surrogate SARS-CoV-2 neutralizing antibody (NAb) is performed to determine the level of NAb in serum sample. Testing is performed using a one-step competitive chemiluminescence immunoassay on the iFlash 1800 analyzer, as described in our previous study.
To assess the safety and adverse events of the vaccination, participants are asked to record any adverse events for 4 weeks after the booster dose.
The primary endpoint of this study is the vMN geometric mean titre (GMT) against WT, BA.1, BA.5.2 and XBB. The secondary endpoints are GMT fold increase and safety. Severe adverse events (SAEs) are defined as death, disabling or life-threatening conditions related to vaccine; Adverse events (AE) include fever (>38 °C), chills, headache, tiredness, nausea, vomit, diarrhea, muscle pain, joint pain, facial dropping, skin rash or injection site reactions (pain, redness, swelling, ecchymoses, itching).
- Conditions
- COVID-19
- Being tested
- ID BNT162b2 vaccine, IM BNT162b2 vaccine
- Keywords
- immunogenicity, safety, intradermal, COVID-19, vaccine, immunocompromised
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ID BNT162b2 vaccineBiological
intradermal BNT162b2 vaccine
IM BNT162b2 vaccineBiological
intramuscular BNT162b2 vaccine
| Study group | Role | What they receive |
|---|---|---|
| Intradermal | Active comparator | One dose of 30ug (0.3mL) intradermal BNT162b2 Receives: Biological: ID BNT162b2 vaccine |
| Intramuscular | Active comparator | One dose of 30ug (0.3mL) intramuscular BNT162b2 Receives: Biological: IM BNT162b2 vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
vMN geometric mean titre
microneutralization GMT
Measured: day 28 after vaccination
Secondary outcomes (2)
vMN geometric meant titre fold increase
microneutralization fold increase
Measured: day 28 after vaccination
Safety of the intradermal vaccination
adverse events
Measured: day 28 after vaccination
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2023
- Study start1 Apr 2021
- Primary completion31 Mar 2023 (estimated)
- Study completion30 Jun 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for COVID-19Studies of the same condition, open and under way.
- More trials run by The University of Hong KongThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- prospective, open-labelled, randomized trial
- Masking
- None (open label)
- Enrolment
- 130 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The University of Hong Kong
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ivan FN Hung, MD, Principal investigator, The University of Hong Kong
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05736913
- Sponsor's protocol ID
- UW 21-214
- Status last verified
- Feb 2023
- First submitted
- 19 Feb 2023
- Last updated
- 8 Mar 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Anonymous patient's immunogenicity and safety data
Publications
Tawinprai K, Siripongboonsitti T, Porntharukchareon T, Wittayasak K, Thonwirak N, Soonklang K, Sornsamdang G, Auewarakul C, Mahanonda N. Immunogenicity and safety of an intradermal fractional third dose of ChAdOx1 nCoV-19/AZD1222 vaccine compared with those of a standard intramuscular third dose in volunteers who previously received two doses of CoronaVac: A randomized controlled trial. Vaccine. 2022 Mar 15;40(12):1761-1767. doi: 10.1016/j.vaccine.2022.02.019. Epub 2022 Feb 21.
PubMed 35210118Niyomnaitham S, Atakulreka S, Wongprompitak P, Copeland KK, Toh ZQ, Licciardi PV, Srisutthisamphan K, Jansarikit L, Chokephaibulkit K. Immunogenicity and reactogenicity of accelerated regimens of fractional intradermal COVID-19 vaccinations. Front Immunol. 2023 Jan 17;13:1080791. doi: 10.3389/fimmu.2022.1080791. eCollection 2022.
PubMed 36733395
Study at a glance
From the registry record, last updated by the sponsor on 8 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Immunogenicity, Safety and Tolerability of Intradermal COVID-19 Vaccination Strategy in Immunocompromised Patients: a Prospective, Randomized Trial.
- ClinicalTrials.gov ID
- NCT05736913
- Acronym / sponsor ID
- UW 21-214
- Conditions
- COVID-19
- Keywords
- immunogenicity, safety, intradermal, COVID-19, vaccine, immunocompromised
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 130 participants (estimated)
- Lead sponsor
- The University of Hong KongUniversity, hospital or other
- Study start
- 1 Apr 2021 (actual)
- Primary completion
- 31 Mar 2023 (estimated)
- Study completion
- 30 Jun 2023 (estimated)
- First posted
- 21 Feb 2023 (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.
COVID-19 is an infectious disease caused by SARS-CoV-2 virus, causing millions of deaths around the globe since the beginning of the pandemic. COVID-19 vaccination was proven to be effective at reducing both mortality and development of severe COVID-19 after infection. Vaccine-elicited protection is particularly important for immunocompromised patients, as they are more susceptible to infections with their defective immune response, for instance, previous review had suggested that patients with malignancies and recipients of solid organ transplants may be at increased risk of developing severe COVID-19 disease and even death.
To further complicate the scenario, there are two obstacles: firstly, immunocompromised individuals may have suboptimal response from vaccinations, as studies have shown that recipients of solid organ transplant have suboptimal or even are seronegative after the fourth dose booster vaccination . Secondly, with constant mutation of the SARS-CoV-2 viruses, new variants evolve over time, leading to reduction in vaccine efficacy and breakthrough infection in healthy individuals. Therefore, novel vaccine strategy should be considered to enhance the vaccine response in these immunocompromised individuals.
In this study, intradermal injection instead of intramuscular injection for vaccine delivery is proposed, as the investigators have observed improved immunogenicity and few adverse events from previous experience of influenza vaccination. The study aims to evaluate the immunogenicity, safety and tolerability of intradermal COVID-19 vaccination in immunocompromised patients.
Detailed description
This is a randomized controlled trial performed in the Hong Kong West Cluster Hospitals under the Hospital Authority in Hong Kong. Immunocompromised individuals who completed two doses of COVID-19 vaccine are recruited and received a booster dose of BNT162b2 vaccine. Recruited individuals include patients who received solid organ transplant (SOT), patients who received stem cell or bone marrow transplant (SCBOT), patients who are undergoing chemotherapy or immunotherapy (COI) and patients who are receiving biologics therapy (BI). The study was approved by the institutional review board of the University of Hong Kong and Hospital Authority (UW 21-214).
After recruitment, participants are randomized to receive either one 30-μg dose (0.3 mL) of intramuscular BNT162b2 booster dose vaccination or one 30-μg dose (0.3 mL) of intradermal BNT162b2 booster dose vaccination. In addition, participants are further subdivided into different groups based on the priming vaccine received. Participant's blood samples are collected before booster vaccination (baseline), 28 days after booster dose, 3 months after booster dose and 6 months after booster dose vaccination. Blood samples collected are tested with live virus microneutralization assay (vMN), performed in the Biosafety level 3 facility of HKU to determine the level of neutralizing antibody in sera. Serial 2-fold dilutions of serum starting from 1:10 are incubated with 100 median tissue culture infectious doses (TCID50) of ancestral strain SARS-CoV-2, BA.1, BA.5.2, and XBB for 1.5 h at 37 °C. Then, a serum-virus mixture is added to VeroE6/TMPRSS2 cells (JCRB Cell Bank Catalogue no. JCRB1819) on 96-well plates. After 72 h of incubation at 37 °C and 5% CO2, the cytopathic effect (CPE) is examined and the antibody titre is determined by the highest dilution with 50% inhibition of CPE. In addition, A Surrogate SARS-CoV-2 neutralizing antibody (NAb) is performed to determine the level of NAb in serum sample. Testing is performed using a one-step competitive chemiluminescence immunoassay on the iFlash 1800 analyzer, as described in our previous study.
To assess the safety and adverse events of the vaccination, participants are asked to record any adverse events for 4 weeks after the booster dose.
The primary endpoint of this study is the vMN geometric mean titre (GMT) against WT, BA.1, BA.5.2 and XBB. The secondary endpoints are GMT fold increase and safety. Severe adverse events (SAEs) are defined as death, disabling or life-threatening conditions related to vaccine; Adverse events (AE) include fever (>38 °C), chills, headache, tiredness, nausea, vomit, diarrhea, muscle pain, joint pain, facial dropping, skin rash or injection site reactions (pain, redness, swelling, ecchymoses, itching).
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- prospective, open-labelled, randomized trial
| Arm | Type | Receives |
|---|---|---|
| Intradermal | Active comparator | Biological: ID BNT162b2 vaccineOne dose of 30ug (0.3mL) intradermal BNT162b2 |
| Intramuscular | Active comparator | Biological: IM BNT162b2 vaccineOne dose of 30ug (0.3mL) intramuscular BNT162b2 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Recruited subjects include adult subjects ≥18 years
- Immunocompromised subjects as defined by the following.
- Negative IgG antibody response against Covid19 14 days after the second dose of Covid19 vaccination.
- All subjects have to give written informed consent.
- Subjects must be available to complete the study and comply with study procedures. Willingness to allow for serum samples to be stored beyond the study period, for potential additional future testing to better characterize immune response
Key exclusion criteria (8 listed)
- Inability to comprehend and to follow all required study procedures.
- Have a recent history (documented, confirmed or suspected) of a flu-like disease within a week of vaccination.
- Have a known allergy to polyethylene glycol (PEG) or other components of the study vaccines, or history of any anaphylaxis, serious vaccine reactions, to any excipients.
- Have known active human immunodeficiency virus (HIV) infection.
- Received an experimental agent (vaccine, drug, biologic, device, blood product, or medication) within 1 month prior to vaccination in this study or expect to receive an experimental agent during this study. Unwilling to refuse participation in another clinical study through the end of this study.
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 |
|---|---|---|
| ID BNT162b2 vaccineintradermal BNT162b2 vaccine | Biological | Intradermal |
| IM BNT162b2 vaccineintramuscular BNT162b2 vaccine | Biological | Intramuscular |
Primary outcome
vMN geometric mean titre
Time frame: day 28 after vaccination
microneutralization GMT
2 secondary outcomes
vMN geometric meant titre fold increase
Time frame: day 28 after vaccination
Safety of the intradermal vaccination
Time frame: day 28 after vaccination
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Mar 2023.
- Results publication: PubMed 35210118Tawinprai K, Siripongboonsitti T, Porntharukchareon T, Wittayasak K, Thonwirak N, Soonklang K, Sornsamdang G, Auewarakul C, Mahanonda N. Immunogenicity and safety of an intradermal fractional third dose of ChAdOx1 nCoV-19/AZD1222 vaccine compared with those of a standard intramuscular third dose in volunteers who previously received two doses of CoronaVac: A randomized controlled trial. Vaccine. 2022 Mar 15;40(12):1761-1767. doi: 10.1016/j.vaccine.2022.02.019. Epub 2022 Feb 21.
- Results publication: PubMed 36733395Niyomnaitham S, Atakulreka S, Wongprompitak P, Copeland KK, Toh ZQ, Licciardi PV, Srisutthisamphan K, Jansarikit L, Chokephaibulkit K. Immunogenicity and reactogenicity of accelerated regimens of fractional intradermal COVID-19 vaccinations. Front Immunol. 2023 Jan 17;13:1080791. doi: 10.3389/fimmu.2022.1080791. eCollection 2022.
- Individual participant dataSharing planned: Yes. Anonymous patient's immunogenicity and safety data
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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.
Ivan FN Hung, MD principal investigator
The University of Hong Kong
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ID BNT162b2 vaccine and IM BNT162b2 vaccine in people with COVID-19, run by The University of Hong Kong at 1 site in Hong Kong.
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 8 inclusion and 8 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 8 Mar 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 Hong Kong. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Ivan FN Hung, MD (22553424, ivanhung@hku.hk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
vMN geometric mean titre (time frame: day 28 after vaccination). 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 NCT05736913, which also lists 2 linked publications.
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 8 Mar 2023.