COVID-19
Conditions
Keywords
Booster dose, Moderna, Pfizer, fractional and standard doses, COVID-19 vaccination, mRNA vaccine
Brief summary
This is a single-blind, randomised controlled clinical trial to determine the reactogenicity and immunogenicity of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) vaccines (Pfizer-BioNTech or Moderna) as booster dose in adults, who have previously received either Pfizer-BioNTech or AstraZeneca as their primary doses. Both fractional and standard doses of Pfizer-BioNTech or Moderna will be tested. The trial intervention will be given in line with Australian Technical Advisory Group on Immunisation (ATAGI) recommendations for booster vaccine doses which allows booster doses from 5 months onwards . There will be a total of 8 groups, with 100 individuals of even spread of participants above and below 50 years in each group. The trial will be single site, based at Royal Children's Hospital, Melbourne, Australia
Detailed description
As per brief summary
Interventions
BIOLOGICALTozinameran - Standard dose
Tozinamrean is a single-stranded, 5'-capped messenger RNA (mRNA) produced using a cell-free in vitro transcription from the corresponding DNA templates, encoding the viral spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS\_CoV-2). A standard dose will be administered on day 0 of the study.
BIOLOGICALTozinameran - fractional dose
Tozinamrean is a single-stranded, 5'-capped messenger RNA (mRNA) produced using a cell-free in vitro transcription from the corresponding DNA templates, encoding the viral spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS\_CoV-2). A fractional dose (15mcg) of the intervention will be administered on day 0 of the study.
BIOLOGICALElasomeran - standard dose
Elasomeran is a single-stranded, 5'-capped messenger RNA (mRNA) produced using a cell-free in vitro transcription from the corresponding DNA templates, encoding the viral spike (S) protein of SARS-CoV-2). A single standard dose (50mcg) of the intervention will be administered on day 0 of the study.
BIOLOGICALElasomeran - fractional dose
Elasomeran is a single-stranded, 5'-capped messenger RNA (mRNA) produced using a cell-free in vitro transcription from the corresponding DNA templates, encoding the viral spike (S) protein of SARS-CoV-2). A fractional dose (20mcg) of the intervention will be administered on day 0 of the study.
Sponsors
Coalition for Epidemic Preparedness Innovations
The Peter Doherty Institute for Infection and Immunity
Murdoch Childrens Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Outcomes Assessor)
Masking description
The participants and those evaluating reactogenicity will be blinded to the vaccine allocation for the first 28 days following vaccination. After that, both clinical investigators and participants will be aware of their investigational product allocation. Laboratory staff will remain blinded to the investigational product allocation during the immunology testing.
Intervention model description
Study participants who have received two doses of either Pfizer or Astrazena vaccine as their primary vaccine will be randomised into one of four groups. The four groups consists of a standard or fractional dose of either Pfizer or Moderna vaccine.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1. Have completed two doses of Pfizer-BioNTech or AstraZeneca vaccines with the recommended schedule 6 months prior to the date of enrolment 2. Willing and able to give written informed consent 3. Aged 18 years or above 4. Willing to complete the follow-up requirements of the study
Exclusion criteria
1. Received 3 doses of COVID-19 vaccine 2. Received 2 doses of COVID-19 less than 6 months prior to the start of the trial 3. Received a different Covid-19 vaccine not available in Australia 4. Currently on immunosuppressive medication or anti-cancer chemotherapy 5. HIV infection 6. Congenital immune deficiency syndrome 7. Has received immunoglobulin or other blood products in the 3 months prior to vaccination 8. Study staff and their relatives 9. Have a history of a severe allergic reaction to any COVID-19 vaccines or have a medical exception to receiving further COVID-19 vaccines 10. Cannot read or understand English
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| SARS-CoV-2 Specific Immunoglobulin (Ig)G Antibodies at 28-days Post Booster Vaccination | 28-days post booster vaccination. | Serum samples collected at 28-days post booster vaccination from all groups will be evaluated for SARS-CoV-2 specific IgG antibodies using the commercial Euroimmun S1 IgG ELISA. Data will be reported as binding antibody units/mL and presented as geometric mean concentration and 95% confidence intervals |
Countries
Australia
Participant flow
Pre-assignment details
Participants who met the inclusion criteria and none of the exclusion criteria were randomised and assigned to one of the eight groups. However, due to the small number of participants enrolled, we have combined the groups based on the vaccine they received during the study and not stratify based on their previous vaccination history.
Participants by arm
| Arm | Count |
|---|---|
| Standard Pfizer-BioNTech Booster Group Due to the small number of participants enrolled, we have combined the groups based on the vaccine they received (i.e. Standard Pfizer-BioNTech booster group) and did not stratify based on their previous vaccination history (i.e. received two doses of AstraZeneca or Pfizer-BioNTech as primary COVID-19 vaccine).
Tozinameran - Standard dose: Tozinamrean is a single-stranded, 5'-capped messenger RNA (mRNA) produced using a cell-free in vitro transcription from the corresponding DNA templates, encoding the viral spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS\_CoV-2). A standard dose will be administered on day 0 of the study. | 4 |
| Fractional Pfizer-BioNTech Booster Group Due to the small number of participants enrolled, we have combined the groups based on the vaccine they received (i.e. fractional Pfizer-BioNTech booster group) and did not stratify based on their previous vaccination history (i.e. received two doses of AstraZeneca or Pfizer-BioNTech as primary COVID-19 vaccine).
Tozinameran - fractional dose: Tozinamrean is a single-stranded, 5'-capped messenger RNA (mRNA) produced using a cell-free in vitro transcription from the corresponding DNA templates, encoding the viral spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS\_CoV-2). A fractional dose (15mcg) of the intervention will be administered on day 0 of the study. | 1 |
| Standard Elasomeran Booster Group Due to the small number of participants enrolled, we have combined the groups based on the vaccine they received (i.e. standard Elasomeran booster group) and did not stratify based on their previous vaccination history (i.e. received two doses of AstraZeneca or Pfizer-BioNTech as primary COVID-19 vaccine).
Elasomeran - standard dose: Elasomeran is a single-stranded, 5'-capped messenger RNA (mRNA) produced using a cell-free in vitro transcription from the corresponding DNA templates, encoding the viral spike (S) protein of SARS-CoV-2).
A single standard dose (50mcg) of the intervention will be administered on day 0 of the study. | 4 |
| Fractional Elasomeran Booster Group Due to the small number of participants enrolled, we have combined the groups based on the vaccine they received (i.e. fractional Elasomeran booster group) and did not stratify based on their previous vaccination history (i.e. received two doses of AstraZeneca or Pfizer-BioNTech as primary COVID-19 vaccine).
Elasomeran - fractional dose: Elasomeran is a single-stranded, 5'-capped messenger RNA (mRNA) produced using a cell-free in vitro transcription from the corresponding DNA templates, encoding the viral spike (S) protein of SARS-CoV-2).
A fractional dose (20mcg) of the intervention will be administered on day 0 of the study. | 4 |
| Total | 13 |
Baseline characteristics
| Characteristic | Fractional Elasomeran Booster Group | Standard Pfizer-BioNTech Booster Group | Fractional Pfizer-BioNTech Booster Group | Standard Elasomeran Booster Group | Total |
|---|---|---|---|---|---|
| Age, Customized Age | 40.6 years | 55.23 years | 33.5 years | 44.7 years | 44.7 years |
| Any reaction to primary vaccine No | 2 Participants | 2 Participants | 1 Participants | 2 Participants | 7 Participants |
| Any reaction to primary vaccine Yes | 2 Participants | 2 Participants | 0 Participants | 2 Participants | 6 Participants |
| Blood pressure pre- COVID-19 booster dose Diastolic | 73.5 mmHG | 83 mmHG | 76 mmHG | 75 mmHG | 76 mmHG |
| Blood pressure pre- COVID-19 booster dose Systolic | 108 mmHG | 125 mmHG | 111 mmHG | 119.5 mmHG | 111 mmHG |
| BMI | 23.0 kg/m2 | 25.5 kg/m2 | 21.9 kg/m2 | 27.8 kg/m2 | 24.4 kg/m2 |
| Currently taking medication No | 4 Participants | 2 Participants | 0 Participants | 2 Participants | 8 Participants |
| Currently taking medication Yes | 0 Participants | 2 Participants | 1 Participants | 2 Participants | 5 Participants |
| Ever tested positive to SARS-CoV-2 | 4 Participants | 0 Participants | 1 Participants | 2 Participants | 7 Participants |
| Medical status at enrolment Anticoagulant therapy | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| Medical status at enrolment Cardiovascular disease | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Medical status at enrolment Cigarette use | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Medical status at enrolment *Gestational diabetes (female only) | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Medical status at enrolment *Pregnant (female only) | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Pulse rate pre COVID-19 booster dose | 71 beats/min | 75 beats/min | 66 beats/min | 66 beats/min | 67 beats/min |
| Race/Ethnicity, Customized Australian | 3 participants | 2 participants | 1 participants | 2 participants | 8 participants |
| Race/Ethnicity, Customized Filipino | 0 participants | 1 participants | 0 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Korean | 0 participants | 1 participants | 0 participants | 1 participants | 2 participants |
| Race/Ethnicity, Customized Polish | 1 participants | 0 participants | 0 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Serbian | 0 participants | 0 participants | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Southern and East African | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Region of Enrollment Australia | 4 participants | 4 participants | 1 participants | 4 participants | 13 participants |
| Respiratory rate pre COVID-19 booster dose | 15 breaths/min | 17 breaths/min | 20 breaths/min | 14 breaths/min | 16 breaths/min |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 3 Participants |
| Sex: Female, Male Male | 3 Participants | 4 Participants | 1 Participants | 2 Participants | 10 Participants |
| Symptoms consistent with COVID-19 | 4 Participants | 0 Participants | 1 Participants | 2 Participants | 7 Participants |
| Temperature | 35.5 celsius | 36.3 celsius | 36.2 celsius | 35.9 celsius | 35.7 celsius |
| Worst clinical spectrum of COVID-19 Mild | 3 Participants | 0 Participants | 1 Participants | 1 Participants | 5 Participants |
| Worst clinical spectrum of COVID-19 Moderate | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 1 | 0 / 4 | 0 / 4 |
| other Total, other adverse events | 1 / 4 | 0 / 1 | 1 / 4 | 0 / 4 |
| serious Total, serious adverse events | 0 / 4 | 0 / 1 | 0 / 4 | 0 / 4 |
Outcome results
Primary
SARS-CoV-2 Specific Immunoglobulin (Ig)G Antibodies at 28-days Post Booster Vaccination
Serum samples collected at 28-days post booster vaccination from all groups will be evaluated for SARS-CoV-2 specific IgG antibodies using the commercial Euroimmun S1 IgG ELISA. Data will be reported as binding antibody units/mL and presented as geometric mean concentration and 95% confidence intervals
Time frame: 28-days post booster vaccination.
Population: IgG antibody response 28-days post booster
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standard Pfizer-BioNTech Booster Group | SARS-CoV-2 Specific Immunoglobulin (Ig)G Antibodies at 28-days Post Booster Vaccination | 1927.1 binding antibody units (BAU/mL) |
| Fractional Pfizer-BioNTech Booster Group | SARS-CoV-2 Specific Immunoglobulin (Ig)G Antibodies at 28-days Post Booster Vaccination | 13707.2 binding antibody units (BAU/mL) |
| Standard Elasomeran Booster Group | SARS-CoV-2 Specific Immunoglobulin (Ig)G Antibodies at 28-days Post Booster Vaccination | 5118.6 binding antibody units (BAU/mL) |
| Fractional Elasomeran Booster Group | SARS-CoV-2 Specific Immunoglobulin (Ig)G Antibodies at 28-days Post Booster Vaccination | 5908.7 binding antibody units (BAU/mL) |