COVID-19
Conditions
Keywords
SARS-CoV-2, vaccine, clinical trial
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.
Interventions
BIOLOGICALmRNA-1273 SARS-CoV-2 vaccine
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.
BIOLOGICALBNT162b2
A white to off-white, sterile, preservative-free, frozen suspension for intramuscular injection, supplied with 0.9% sodium chloride diluent for injection plastic ampoules.
BIOLOGICALChAdOx1-S [recombinant]
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).
OTHER0, 28 day schedule
Second injection administered 28 days post first injection
OTHER0, 112 day schedule
Second injection administered 112 days post first injection
BIOLOGICALCovifenz
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
Sponsors
Canadian Center for Vaccinology
BC Children's Hospital Research Institute
Children's Hospital Research Institute of Manitoba
CHU de Quebec-Universite Laval
Ottawa Hospital Research Institute
Ontario Agency for Health Protection and Promotion
University of Toronto
Massachusetts General Hospital
Interior Health
McGill University Health Centre/Research Institute of the McGill University Health Centre
Canadian Immunization Research Network
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
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.
Intervention model description
M=Moderna SpikeVax mRNA; P=Pfizer/BioNTech Comirnaty mRNA; A=AstraZeneca Vaxzervia; C=Medicago Covifenz VLP MOSAIC 1: * Group 1 - M, M - 28 days * Group 2 - M, M - 112 days * Group 3 - M, P - 28 days * Group 4 - M, P - 112 days * Group 5 - P, P - 28 days * Group 6 - P, P - 112 days * Group 7 - P, M - 28 days * Group 8 - P, M - 112 days * Group 9 - A, M - 28 days * Group 10 - A, M - 112 days * Group 11 - A, P - 28 days * Group 12 - A, P - 112 days MOSAIC 2: * Group 1b - P, P, P * Group 2b - P, P, M * Group 3b - M, M, M * Group 4b - M, M, P * Group 5b - P and M in any order, M * Group 6b - P and M in any order, P * Group 7b - A, P or M, P * Group 8b - A, P or M, M * Group 9b - Any vaccine in any order, C (open-label) MOSAIC 3: * Group 1c - P, P, P, P * Group 2c - P, P, P, C * Group 3c - M, M, M, M * Group 4c - M, M, M, C * Group 5c - Any 3 in any order, P or M * Group 6c - Any 3 in any order, C * Group 7c - Any 3 in any order, C (open-label)
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
Yes
Inclusion criteria
1. Participant is willing and able to give written informed consent to participate in the study 2. Age 18 years of age or older in good health or with mild or moderate stable co-morbidities at the time of enrolment 3. Able and willing to complete all the scheduled study procedures during the whole study follow-up period 4. 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) 5. 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) 6. MOSAIC -1 Vaccine naïve subgroups: have not received an authorized COVID-19 vaccine at any time 7. 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) 8. 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
1. Inability or unwillingness of participant or legally acceptable representative to give written informed consent 2. 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 3. Current diagnosis or treatment for cancer (except basal cell carcinoma of the skin) 4. 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 5. Allergy to any study vaccine or any active substance in a study vaccine 6. Bleeding disorder or history of significant bleeding following IM injections or venipuncture 7. Continuous use of anticoagulants 8. A history of anaphylaxis to a previous vaccine 9. Pregnancy or intent to become pregnant during the study or within 3 months of the last dose of study vaccine 10. MOSAIC-1: History of laboratory-confirmed COVID-19 disease prior to enrolment by participant report 11. Administration of a live virus vaccine within 4 weeks prior to study vaccine receipt.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Antibody response to SARS-CoV-2 S protein after 4 doses | 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 | Day 56 | 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. |
| Antibody response to SARS-CoV-2 S protein after 3 doses | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. | 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). |
| 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. | 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). |
| Acceptability of vaccines as determined by participant-completed questionnaire after 2 doses | Days 56, 140, and 365 | 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. |
| Acceptability of vaccines as determined by participant-completed questionnaire after 3 doses | Days 28, 180 | 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. |
| Antibody to SARS-CoV-2 S and N, RBD after 3 doses | Days 180 and 365 | Assess durability of the immune responses in each study group over 12 months after the study vaccine. |
| Pseudoneutralization assay, T cell testing, Antibody dependent cellular cytotoxicity after 3 doses | Day 365 | Further characterize the immune response to COVID-19 vaccine in schedules with homologous and heterologous third doses to day 365 |
| Acceptability of vaccines as determined by participant-completed questionnaire after 4 doses | Days 28, 180 | 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). |
| Antibody to SARS-CoV-2 S and N, RBD after 4 doses | Days 180 and 365 | Assess durability of the immune responses in each study group over 12 months after the study vaccine. |
| Antibody dependent cellular cytotoxicity after 4 doses | Day 365 | Further characterize the immune response to COVID-19 vaccine in schedules with homologous and heterologous third doses to day 365 |
| Pseudoneutralization assay after 4 doses | Day 365 | 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 |
| T cell testing after 4 doses | Day 365 | 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 |
| 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. | 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). |
| Durability of antibody response to SARS-CoV-2 S over 12 months after 2 doses | Baseline and Days 28, 56, 112, 140, 365 | Assess durability of immune responses in each study group over 12 months based on anti-spike antibody titers and pseudoneutralization assay. |
| Pseudoneutralization assay, T cell testing, Antibody dependent cellular cytotoxicity (ADCC), Antibody avidity, RNA seq after 2 doses | Days 28, 56, 112, 140, 365 | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Exploratory assessment of interval between dose 1 and 2 on immune response after 3 or 4 doses | From time of first study injection through Day 365. | 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. |
Countries
Canada
Outcome results
None listed