Immunogenicity and Adverse Events Following Immunization (AEFI) With Alternate Schedules of COVID-19 Vaccines in Canada: is "Mix and Match" of the Second Dose (MOSAIC-1;CT24a) and Additional Doses (MOSAIC-2 and MOSAIC-3;CT24b and CT24c) Safe and Immunogenic?
Overview
- Phase
- Phase 2
- Intervention
- mRNA-1273 SARS-CoV-2 vaccine
- Conditions
- COVID-19
- Sponsor
- Canadian Immunization Research Network
- Enrollment
- 669
- Locations
- 8
- Primary Endpoint
- Antibody response to SARS-CoV-2 S protein after 3 doses
- Status
- Active, not recruiting
- Last Updated
- last year
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Participant is willing and able to give written informed consent to participate in the study
- •Age 18 years of age or older in good health or with mild or moderate stable co-morbidities at the time of enrolment
- •Able and willing to complete all the scheduled study procedures during the whole study follow-up period
- •If female of child-bearing potential and heterosexually active, has practiced adequate contraception for 30 days prior to injection, has a negative pregnancy test on the day of injection, and has agreed to continue adequate contraception until 3 months after the final dose of study vaccine (Please refer to the definition section for a description of child-bearing potential and adequate contraception)
- •MOSAIC-1 Vaccine-exposed subgroups: have received or are booked to receive the first dose of an authorized COVID-19 vaccine in the 55 days prior to Visit 1 (documentation of receipt required)
- •MOSAIC -1 Vaccine naïve subgroups: have not received an authorized COVID-19 vaccine at any time
- •MOSAIC-2 participants have received two doses of COVID-19 vaccines authorized in Canada ≥6 months prior to study vaccine administration (documentation of receipt required)
- •MOSAIC-3 participants have received three doses of COVID-19 vaccines authorized in Canada ≥3 months prior to study vaccine administration (documentation of receipt required)
Exclusion Criteria
- •Inability or unwillingness of participant or legally acceptable representative to give written informed consent
- •Any confirmed or suspected immunosuppressive or immunodeficient state; asplenia, or immunosuppressant medication within the past 6 months except short term oral steroids (≤14 days duration) or topical steroids
- •Current diagnosis or treatment for cancer (except basal cell carcinoma of the skin)
- •Administration of immunoglobulins and/or any blood products within 3 months preceding the first dose of study vaccine and for one month after the last dose of study vaccine
- •Allergy to any study vaccine or any active substance in a study vaccine
- •Bleeding disorder or history of significant bleeding following IM injections or venipuncture
- •Continuous use of anticoagulants
- •A history of anaphylaxis to a previous vaccine
- •Pregnancy or intent to become pregnant during the study or within 3 months of the last dose of study vaccine
- •MOSAIC-1: History of laboratory-confirmed COVID-19 disease prior to enrolment by participant report
Arms & Interventions
Group 1: Moderna, Moderna - 28 Days apart
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.
Intervention: mRNA-1273 SARS-CoV-2 vaccine
Group 1: Moderna, Moderna - 28 Days apart
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.
Intervention: 0, 28 day schedule
Group 2: Moderna, Moderna - 112 days apart
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.
Intervention: mRNA-1273 SARS-CoV-2 vaccine
Group 2: Moderna, Moderna - 112 days apart
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.
Intervention: 0, 112 day schedule
Group 3: Moderna, Pfizer/BioNTech - 28 days apart
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.
Intervention: mRNA-1273 SARS-CoV-2 vaccine
Group 3: Moderna, Pfizer/BioNTech - 28 days apart
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.
Intervention: BNT162b2
Group 3: Moderna, Pfizer/BioNTech - 28 days apart
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.
Intervention: 0, 28 day schedule
Group 4: Moderna, Pfizer/BioNTech - 112 days apart
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.
Intervention: mRNA-1273 SARS-CoV-2 vaccine
Group 4: Moderna, Pfizer/BioNTech - 112 days apart
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.
Intervention: BNT162b2
Group 4: Moderna, Pfizer/BioNTech - 112 days apart
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.
Intervention: 0, 112 day schedule
Group 5: Pfizer/BioNTech, Pfizer/BioNTech - 28 days apart
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.
Intervention: BNT162b2
Group 8: Pfizer/BioNTech, Moderna - 112 days apart
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.
Intervention: 0, 112 day schedule
Group 5: Pfizer/BioNTech, Pfizer/BioNTech - 28 days apart
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.
Intervention: 0, 28 day schedule
Group 6: Pfizer/BioNTech, Pfizer/BioNTech - 112 days apart
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.
Intervention: BNT162b2
Group 6: Pfizer/BioNTech, Pfizer/BioNTech - 112 days apart
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.
Intervention: 0, 112 day schedule
Group 7: Pfizer/BioNTech, Moderna - 28 days apart
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.
Intervention: mRNA-1273 SARS-CoV-2 vaccine
Group 7: Pfizer/BioNTech, Moderna - 28 days apart
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.
Intervention: BNT162b2
Group 7: Pfizer/BioNTech, Moderna - 28 days apart
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.
Intervention: 0, 28 day schedule
Group 8: Pfizer/BioNTech, Moderna - 112 days apart
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.
Intervention: mRNA-1273 SARS-CoV-2 vaccine
Group 8: Pfizer/BioNTech, Moderna - 112 days apart
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.
Intervention: BNT162b2
Group 9: Astra Zeneca, Moderna - 28 days apart
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.
Intervention: mRNA-1273 SARS-CoV-2 vaccine
Group 9: Astra Zeneca, Moderna - 28 days apart
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.
Intervention: ChAdOx1-S [recombinant]
Group 9: Astra Zeneca, Moderna - 28 days apart
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.
Intervention: 0, 28 day schedule
Group 10: Astra Zeneca, Moderna - 112 days apart
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.
Intervention: mRNA-1273 SARS-CoV-2 vaccine
Group 10: Astra Zeneca, Moderna - 112 days apart
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.
Intervention: ChAdOx1-S [recombinant]
Group 10: Astra Zeneca, Moderna - 112 days apart
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.
Intervention: 0, 112 day schedule
Group 11: Astra Zeneca, Pfizer/BioNTech - 28 days apart
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.
Intervention: BNT162b2
Group 11: Astra Zeneca, Pfizer/BioNTech - 28 days apart
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.
Intervention: ChAdOx1-S [recombinant]
Group 11: Astra Zeneca, Pfizer/BioNTech - 28 days apart
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.
Intervention: 0, 28 day schedule
Group 12: Astra Zeneca, Pfizer/BioNTech - 112 days apart
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.
Intervention: BNT162b2
Group 12: Astra Zeneca, Pfizer/BioNTech - 112 days apart
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.
Intervention: ChAdOx1-S [recombinant]
Group 12: Astra Zeneca, Pfizer/BioNTech - 112 days apart
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.
Intervention: 0, 112 day schedule
Group 1b
Participants will be blinded and receive one dose (0.3mL) of BNT162b2 vaccine via intramuscular injection in the deltoid muscle.
Intervention: BNT162b2
Group 2b
Participants will be blinded and receive one half dose (0.25mL) of mRNA-1273 vaccine via intramuscular injection in the deltoid muscle.
Intervention: mRNA-1273 SARS-CoV-2 vaccine
Group 3b
Participants will be blinded and receive one half dose (0.25mL) of mRNA-1273 vaccine via intramuscular injection in the deltoid muscle.
Intervention: mRNA-1273 SARS-CoV-2 vaccine
Group 4b
Participants will be blinded and receive one dose (0.3mL) of BNT162b2 vaccine via intramuscular injection in the deltoid muscle.
Intervention: BNT162b2
Group 5b
Participants will be blinded and receive one half dose (0.25mL) of mRNA-1273 vaccine via intramuscular injection in the deltoid muscle.
Intervention: mRNA-1273 SARS-CoV-2 vaccine
Group 6b
Participants will be blinded and receive one dose (0.3mL) of BNT162b2 vaccine via intramuscular injection in the deltoid muscle.
Intervention: BNT162b2
Group 7b
Participants will be blinded and receive one dose (0.3mL) of BNT162b2 vaccine via intramuscular injection in the deltoid muscle.
Intervention: BNT162b2
Group 8b
Participants will be blinded and receive one half dose (0.25mL) of mRNA-1273 vaccine via intramuscular injection in the deltoid muscle.
Intervention: mRNA-1273 SARS-CoV-2 vaccine
Group 9b
Participants will receive one dose (0.5mL) of Covifenz vaccine via intramuscular injection in the deltoid muscle.
Intervention: Covifenz
Group 1c
Participants will be blinded and receive one dose (0.3mL) of BNT162b2 vaccine via intramuscular injection in the deltoid muscle.
Intervention: BNT162b2
Group 2c
Participants will be blinded and receive one dose (0.5mL) of Covifenz vaccine via intramuscular injection in the deltoid muscle.
Intervention: Covifenz
Group 3c
Participants will be blinded and receive one half dose (0.25mL) of mRNA-1273 vaccine via intramuscular injection in the deltoid muscle.
Intervention: mRNA-1273 SARS-CoV-2 vaccine
Group 4c
Participants will be blinded and receive one dose (0.5mL) of Covifenz vaccine via intramuscular injection in the deltoid muscle.
Intervention: Covifenz
Group 5c
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.
Intervention: mRNA-1273 SARS-CoV-2 vaccine
Group 5c
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.
Intervention: BNT162b2
Group 6c
Participants will be blinded and receive one dose (0.5mL) of Covifenz vaccine via intramuscular injection in the deltoid muscle.
Intervention: Covifenz
Group 7c
Participants will receive one dose (0.5mL) of Covifenz vaccine via intramuscular injection in the deltoid muscle.
Intervention: Covifenz
Outcomes
Primary Outcomes
Antibody response to SARS-CoV-2 S protein after 3 doses
Time Frame: Day 28
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.
Antibody response to SARS-CoV-2 S protein after 4 doses
Time Frame: Day 28
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.
Antibody response to SARS-CoV-2 S protein after 2 doses
Time Frame: Day 140
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.
Secondary Outcomes
- Durability of antibody response to SARS-CoV-2 S over 12 months after 2 doses(Baseline and Days 28, 56, 112, 140, 365)
- Antibody to SARS-CoV-2 S and N, RBD after 3 doses(Days 180 and 365)
- Pseudoneutralization assay, T cell testing, Antibody dependent cellular cytotoxicity after 3 doses(Day 365)
- Acceptability of vaccines as determined by participant-completed questionnaire after 3 doses(Days 28, 180)
- Incidence of grade 3 solicited local and systemic adverse events, SAEs, AEFIs, MAAEs, AESIs in the 7 days following vaccine receipt after 4 doses(From time of first study injection through Day 365.)
- Pseudoneutralization assay, T cell testing, Antibody dependent cellular cytotoxicity (ADCC), Antibody avidity, RNA seq after 2 doses(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(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(From time of first study injection through Day 365.)
- Acceptability of vaccines as determined by participant-completed questionnaire after 2 doses(Days 56, 140, and 365)
- Acceptability of vaccines as determined by participant-completed questionnaire after 4 doses(Days 28, 180)
- Antibody to SARS-CoV-2 S and N, RBD after 4 doses(Days 180 and 365)
- Antibody dependent cellular cytotoxicity after 4 doses(Day 365)
- Pseudoneutralization assay after 4 doses(Day 365)
- T cell testing after 4 doses(Day 365)