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| Name | Class |
|---|---|
| Canadian Center for Vaccinology | OTHER |
| BC Children's Hospital Research Institute | OTHER |
| Children's Hospital Research Institute of Manitoba | OTHER |
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The main goals of this study are to assess the immune response and safety of two different vaccines for first, second, third and fourth doses as well as for differing intervals between the first and second dose of two-dose vaccines.
For dose 1 and 2, the currently available mRNA vaccines (Pfizer-BioNTech BNT162b2 and Moderna mRNA-1273) are two dose vaccines which were studied in schedules of either 0 and 21 days or 0 and 28 days, respectively. The ChAdOx1 nCOV-19 (Astra-Zeneca) adenovirus-vectored vaccine is authorized to be given in two doses one month to 12 weeks apart. We will compare the interval 0, 28 days to a 0, 112 days (16 weeks) schedule, and assess the immunogenicity of both heterogeneous and heterologous second doses using the Canadian schedule.
For dose 3, the currently available mRNA vaccines (Pfizer-BioNTech BNT162b2 and Moderna mRNA-1273) and plant-based virus-like particle (Medicago Covifenz) are anticipated to be administered 6 months apart. We will assess the immunogenicity of both heterogeneous and heterologous third doses using the Canadian schedule.
For dose 4, the currently available mRNA vaccines (Pfizer-BioNTech BNT162b2 and Moderna mRNA-1273) and plant-based virus-like particle (Medicago Covifenz) are anticipated to be administered 3 months apart. We will assess the immunogenicity of both heterogeneous and heterologous third doses using the Canadian schedule.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group 1: Moderna, Moderna - 28 Days apart | Active Comparator | Participants will be blinded and receive two doses (0.20 mg/mL each) of mRNA-1273 SARS-CoV-2 vaccine via intramuscular injection in the deltoid muscle 28 days apart. Vaccine-exposed participants will only be blinded to, and receive, the second injection. |
|
| Group 2: Moderna, Moderna - 112 days apart | Active Comparator | Participants will be blinded and receive two doses (0.20 mg/mL each) of mRNA-1273 SARS-CoV-2 vaccine at 0.20 mg/mL via intramuscular injection in the deltoid muscle 112 days apart. Vaccine-exposed participants will only be blinded to, and receive, the second injection. |
|
| Group 3: Moderna, Pfizer/BioNTech - 28 days apart | Active Comparator | Participants will be blinded and receive one dose (0.20 mg/mL) of mRNA-1273 SARS-CoV-2 vaccine via intramuscular injection in the deltoid muscle followed by one dose (0.3mL) of BNT162b2 vaccine after 28 days. Vaccine-exposed participants will only be blinded to, and receive, the second injection. |
|
| Group 4: Moderna, Pfizer/BioNTech - 112 days apart | Active Comparator | Participants will be blinded and receive one dose (0.20 mg/mL) of mRNA-1273 SARS-CoV-2 vaccine via intramuscular injection in the deltoid muscle followed by one dose (0.3mL) of BNT162b2 vaccine after 112 days. Vaccine-exposed participants will only be blinded to, and receive, the second injection. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| mRNA-1273 SARS-CoV-2 vaccine | Biological | Contains 1.26 mg of CX-024414 mRNA and 24.38 mg of SM-102 LNP as a white to off-white dispersion in preservative-free diluent buffer at pH 7.5. |
| Measure | Description | Time Frame |
|---|---|---|
| Antibody response to SARS-CoV-2 S protein after 2 doses | The co-primary outcome for the non-inferiority comparison of 0, 28-day schedules with heterologous second dose is the immune response to SARS-CoV-2 at day 56 (28 days after the second dose of vaccine) based on anti-spike antibody titers. | Day 56 |
| Antibody response to SARS-CoV-2 S protein after 2 doses | The co-primary outcome for the non-inferiority comparison of schedules in which the timing of the second dose of vaccine is different (0, 28 days v 0, 112 days) is the immune response to SARS-CoV-2 at day 140 (28 days after the last dose in the 0, 112 day schedule) based on anti-spike antibody titers. | Day 140 |
| Antibody response to SARS-CoV-2 S protein after 3 doses | To determine if a vaccination schedule with a heterologous third dose of a COVID-19 vaccine induces a non-inferior serum immune response to SARS-CoV-2, compared to a third dose/booster with a homologous vaccine. | Day 28 |
| Antibody response to SARS-CoV-2 S protein after 4 doses | To determine if a vaccination schedule with a heterologous fourth dose of a COVID-19 vaccine induces a non-inferior serum immune response to SARS-CoV-2, compared to a third dose/booster with a homologous vaccine. | Day 28 |
| Measure | Description | Time Frame |
|---|---|---|
| Durability of antibody response to SARS-CoV-2 S over 12 months after 2 doses | Assess durability of immune responses in each study group over 12 months based on anti-spike antibody titers and pseudoneutralization assay. | Baseline and Days 28, 56, 112, 140, 365 |
| Pseudoneutralization assay, T cell testing, Antibody dependent cellular cytotoxicity (ADCC), Antibody avidity, RNA seq after 2 doses |
| Measure | Description | Time Frame |
|---|---|---|
| Exploratory assessment of interval between dose 1 and 2 on immune response after 3 or 4 doses | Assess the role of intervals between first and second doses of the primary immunization schedule, and between 2nd and 3rd doses, on immune responses after the third dose over the study period. | From time of first study injection through Day 365. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Joanne Langley | Dalhousie University/CIRN | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Royal Inland Hospital | Kamloops | British Columbia | Canada | |||
| Penticton Regional Hospital |
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| ID | Term |
|---|---|
| D000086382 | COVID-19 |
| ID | Term |
|---|---|
| D011024 | Pneumonia, Viral |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
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| ID | Term |
|---|---|
| D000090983 | 2019-nCoV Vaccine mRNA-1273 |
| D000090982 | BNT162 Vaccine |
| D000090985 | ChAdOx1 nCoV-19 |
| D001071 | Appointments and Schedules |
| ID | Term |
|---|---|
| D000087503 | mRNA Vaccines |
| D000087504 | Nucleic Acid-Based Vaccines |
| D014614 | Vaccines, Synthetic |
| D011994 | Recombinant Proteins |
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| CHU de Quebec-Universite Laval |
| OTHER |
| Ottawa Hospital Research Institute | OTHER |
| Ontario Agency for Health Protection and Promotion | OTHER_GOV |
| University of Toronto | OTHER |
| Massachusetts General Hospital | OTHER |
| Interior Health | INDUSTRY |
| McGill University Health Centre/Research Institute of the McGill University Health Centre | OTHER |
M=Moderna SpikeVax mRNA; P=Pfizer/BioNTech Comirnaty mRNA; A=AstraZeneca Vaxzervia; C=Medicago Covifenz VLP
MOSAIC 1:
MOSAIC 2:
MOSAIC 3:
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Participants, laboratory staff, and statistical analysis personnel will be blinded to which vaccine they are receiving for those in randomized arms.
Laboratory staff and statistical analysis personnel will be blinded to which vaccine they are receiving for those in open-label arms.
|
| Group 5: Pfizer/BioNTech, Pfizer/BioNTech - 28 days apart | Active Comparator | Participants will be blinded and receive two doses (0.3mL each) of BNT162b2 vaccine via intramuscular injection in the deltoid muscle 28 days apart. Vaccine-exposed participants will only be blinded to, and receive, the second injection. |
|
| Group 6: Pfizer/BioNTech, Pfizer/BioNTech - 112 days apart | Active Comparator | Participants will be blinded and receive two doses (0.3mL each) of BNT162b2 vaccine via intramuscular injection in the deltoid muscle 112 days apart. Vaccine-exposed participants will only be blinded to, and receive, the second injection. |
|
| Group 7: Pfizer/BioNTech, Moderna - 28 days apart | Active Comparator | Participants will be blinded and receive one dose (0.3mL) of BNT162b2 vaccine via intramuscular injection in the deltoid muscle followed by one dose (0.20 mg/mL) of mRNA-1273 SARS-CoV-2 vaccine after 28 days. Vaccine-exposed participants will only be blinded to, and receive, the second injection. |
|
| Group 8: Pfizer/BioNTech, Moderna - 112 days apart | Active Comparator | Participants will be blinded and receive one dose (0.3mL) of BNT162b2 vaccine via intramuscular injection in the deltoid muscle followed by one dose (0.20 mg/mL) of mRNA-1273 SARS-CoV-2 vaccine after 112 days. Vaccine-exposed participants will only be blinded to, and receive, the second injection. |
|
| Group 9: Astra Zeneca, Moderna - 28 days apart | Active Comparator | Participants will be blinded and receive one dose (0.5 ml) of ChAdOx1-S [recombinant] vaccine via intramuscular injection in the deltoid muscle followed by one dose (0.20 mg/mL) of mRNA-1273 SARS-CoV-2 vaccine after 28 days. Vaccine-exposed participants will only be blinded to, and receive, the second injection. |
|
| Group 10: Astra Zeneca, Moderna - 112 days apart | Active Comparator | Participants will be blinded and receive one dose (0.5 ml) of ChAdOx1-S [recombinant] vaccine via intramuscular injection in the deltoid muscle followed by one dose (0.20 mg/mL) of mRNA-1273 SARS-CoV-2 vaccine after 112 days. Vaccine-exposed participants will only be blinded to, and receive, the second injection. |
|
| Group 11: Astra Zeneca, Pfizer/BioNTech - 28 days apart | Active Comparator | Participants will be blinded and receive one dose (0.5 ml) of ChAdOx1-S [recombinant] vaccine via intramuscular injection in the deltoid muscle followed by one dose (0.3 mL) of BNT162b2 vaccine after 28 days. Vaccine-exposed participants will only be blinded to, and receive, the second injection. |
|
| Group 12: Astra Zeneca, Pfizer/BioNTech - 112 days apart | Active Comparator | Participants will be blinded and receive one dose (0.5 ml) of ChAdOx1-S [recombinant] vaccine via intramuscular injection in the deltoid muscle followed by one dose (0.3 mL) of BNT162b2 vaccine after 112 days. Vaccine-exposed participants will only be blinded to, and receive, the second injection. |
|
| Group 1b | Active Comparator | Participants will be blinded and receive one dose (0.3mL) of BNT162b2 vaccine via intramuscular injection in the deltoid muscle. |
|
| Group 2b | Active Comparator | Participants will be blinded and receive one half dose (0.25mL) of mRNA-1273 vaccine via intramuscular injection in the deltoid muscle. |
|
| Group 3b | Active Comparator | Participants will be blinded and receive one half dose (0.25mL) of mRNA-1273 vaccine via intramuscular injection in the deltoid muscle. |
|
| Group 4b | Active Comparator | Participants will be blinded and receive one dose (0.3mL) of BNT162b2 vaccine via intramuscular injection in the deltoid muscle. |
|
| Group 5b | Active Comparator | Participants will be blinded and receive one half dose (0.25mL) of mRNA-1273 vaccine via intramuscular injection in the deltoid muscle. |
|
| Group 6b | Active Comparator | Participants will be blinded and receive one dose (0.3mL) of BNT162b2 vaccine via intramuscular injection in the deltoid muscle. |
|
| Group 7b | Active Comparator | Participants will be blinded and receive one dose (0.3mL) of BNT162b2 vaccine via intramuscular injection in the deltoid muscle. |
|
| Group 8b | Active Comparator | Participants will be blinded and receive one half dose (0.25mL) of mRNA-1273 vaccine via intramuscular injection in the deltoid muscle. |
|
| Group 9b | Experimental | Participants will receive one dose (0.5mL) of Covifenz vaccine via intramuscular injection in the deltoid muscle. |
|
| Group 1c | Active Comparator | Participants will be blinded and receive one dose (0.3mL) of BNT162b2 vaccine via intramuscular injection in the deltoid muscle. |
|
| Group 2c | Active Comparator | Participants will be blinded and receive one dose (0.5mL) of Covifenz vaccine via intramuscular injection in the deltoid muscle. |
|
| Group 3c | Active Comparator | Participants will be blinded and receive one half dose (0.25mL) of mRNA-1273 vaccine via intramuscular injection in the deltoid muscle. |
|
| Group 4c | Active Comparator | Participants will be blinded and receive one dose (0.5mL) of Covifenz vaccine via intramuscular injection in the deltoid muscle. |
|
| Group 5c | Active Comparator | Participants will be blinded and receive either one dose (0.3mL) of BNT162b2 or one half dose (0.25mL) of mRNA-1273 via intramuscular injection in the deltoid muscle. |
|
| Group 6c | Active Comparator | Participants will be blinded and receive one dose (0.5mL) of Covifenz vaccine via intramuscular injection in the deltoid muscle. |
|
| Group 7c | Experimental | Participants will receive one dose (0.5mL) of Covifenz vaccine via intramuscular injection in the deltoid muscle. |
|
|
| BNT162b2 | Biological | A white to off-white, sterile, preservative-free, frozen suspension for intramuscular injection, supplied with 0.9% sodium chloride diluent for injection plastic ampoules. |
|
|
| ChAdOx1-S [recombinant] | Biological | A colourless to slightly brown, clear to slightly opaque solution containing 5 x 1010 viral particles (not less than 2.5 x 108 infectious units). |
|
|
| 0, 28 day schedule | Other | Second injection administered 28 days post first injection |
|
| 0, 112 day schedule | Other | Second injection administered 112 days post first injection |
|
| Covifenz | Biological | COVIFENZ is an emulsion for intramuscular injection. The 3.75 mcg antigen component of COVIFENZ is a suspension, which must be mixed 1:1 with the 0.25 mL AS03 adjuvant emulsion component prior to administration |
|
|
Characterization of the immune response to COVID-19 vaccines in schedules with 0, 28 days versus 0, 112 days dosing and heterologous schedules to day 365. |
| Days 28, 56, 112, 140, 365 |
| Incidence of grade 3 solicited local and systemic adverse events, SAEs, AEFIs, MAAEs, AESIs in the 7 days following vaccine receipt after 2 doses | Description of safety outcomes over 12 months post-vaccination including SAEs (serious adverse events), provincially reportable AEFIs (adverse events following immunization), MAAEs (medically attended adverse events), AESIs (adverse events of special interest). | From time of first study injection through Day 365. |
| Incidence of grade 3 solicited local and systemic adverse events, SAEs, AEFIs, MAAEs, AESIs in the 7 days following vaccine receipt after 3 doses | Description of safety outcomes over 12 months post-vaccination including SAEs (serious adverse events), provincially reportable AEFIs (adverse events following immunization), MAAEs (medically attended adverse events), AESIs (adverse events of special interest). | From time of first study injection through Day 365. |
| Acceptability of vaccines as determined by participant-completed questionnaire after 2 doses | Four 5 point likert scale type questions asking whether they would want to receive the vaccine again, recommend it to a friend, whether they were anxious about receiving it, and whether they would prefer a more painful injection if it conferred better protection. | Days 56, 140, and 365 |
| Acceptability of vaccines as determined by participant-completed questionnaire after 3 doses | Four 5 point likert scale type questions asking whether they would want to receive the vaccine again, recommend it to a friend, whether they were anxious about receiving it, and whether they would prefer a more painful injection if it conferred better protection. | Days 28, 180 |
| Antibody to SARS-CoV-2 S and N, RBD after 3 doses | Assess durability of the immune responses in each study group over 12 months after the study vaccine. | Days 180 and 365 |
| Pseudoneutralization assay, T cell testing, Antibody dependent cellular cytotoxicity after 3 doses | Further characterize the immune response to COVID-19 vaccine in schedules with homologous and heterologous third doses to day 365 | Day 365 |
| Incidence of grade 3 solicited local and systemic adverse events, SAEs, AEFIs, MAAEs, AESIs in the 7 days following vaccine receipt after 4 doses | Description of safety outcomes over 12 months post-vaccination including SAEs (serious adverse events), provincially reportable AEFIs (adverse events following immunization), MAAEs (medically attended adverse events), AESIs (adverse events of special interest). | From time of first study injection through Day 365. |
| Acceptability of vaccines as determined by participant-completed questionnaire after 4 doses | Four 5 point likert scale type questions asking whether they would want to receive the vaccine again(Yes, definitely; Yes, probably; I don't know; No, probably not; No, definitely not), recommend it to a friend(Yes, definitely; Yes, probably; I don't know; No, probably not; No, definitely not), whether they were anxious about receiving it(Not at all; A little; Moderately; Very; Extremely), and whether they would prefer a more painful injection if it conferred better protection(Vaccine A; Vaccine B; No preference; Unsure/don't know). | Days 28, 180 |
| Antibody to SARS-CoV-2 S and N, RBD after 4 doses | Assess durability of the immune responses in each study group over 12 months after the study vaccine. | Days 180 and 365 |
| Antibody dependent cellular cytotoxicity after 4 doses | Further characterize the immune response to COVID-19 vaccine in schedules with homologous and heterologous third doses to day 365 | Day 365 |
| Pseudoneutralization assay after 4 doses | Measuring the 50% Neutralization Titer to further characterize the immune response to COVID-19 vaccine in schedules with homologous and heterologous third doses to day 365 | Day 365 |
| T cell testing after 4 doses | Measuring the number of T cells to further characterize the immune response to COVID-19 vaccine in schedules with homologous and heterologous third doses to day 365 | Day 365 |
| Penticton |
| British Columbia |
| Canada |
| BC Children's Hospital Research Institute | Vancouver | British Columbia | V5Z 4H4 | Canada |
| Children's Hospital Research Institute of Manitoba | Winnipeg | Manitoba | Canada |
| Canadian Center for Vaccinology | Halifax | Nova Scotia | Canada |
| Ottawa Hospital Research Institute, University of Ottawa | Ottawa | Ontario | Canada |
| McGill University Health Centre Vaccine Study Centre | Montreal | Quebec | H9H 4Y6 | Canada |
| CHU de Québec, Université Laval | Québec | Quebec | Canada |
| D014777 |
| Virus Diseases |
| D018352 | Coronavirus Infections |
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D014612 | Vaccines |
| D001688 | Biological Products |
| D045424 | Complex Mixtures |
| D000086663 | COVID-19 Vaccines |
| D014765 | Viral Vaccines |
| D000941 | Antigens |
| D001685 | Biological Factors |
| D019444 | Vaccines, DNA |
| D009934 | Organization and Administration |
| D006298 | Health Services Administration |