Mix and Match of the COVID-19 Vaccine for Safety and Immunogenicity
MOSAIC
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?
1 other identifier
interventional
669
1 country
8
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2 covid19
Started May 2021
Longer than P75 for phase_2 covid19
8 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 18, 2021
CompletedFirst Posted
Study publicly available on registry
May 20, 2021
CompletedStudy Start
First participant enrolled
May 20, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 15, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
August 1, 2025
CompletedMarch 18, 2025
March 1, 2025
3.5 years
May 18, 2021
March 14, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (4)
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
Secondary Outcomes (14)
Durability of antibody response to SARS-CoV-2 S over 12 months after 2 doses
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
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
- +9 more secondary outcomes
Other Outcomes (1)
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.
Study Arms (28)
Group 1: Moderna, Moderna - 28 Days apart
ACTIVE COMPARATORParticipants 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 COMPARATORParticipants 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 COMPARATORParticipants 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 COMPARATORParticipants 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.
Group 5: Pfizer/BioNTech, Pfizer/BioNTech - 28 days apart
ACTIVE COMPARATORParticipants 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 COMPARATORParticipants 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 COMPARATORParticipants 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 COMPARATORParticipants 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 COMPARATORParticipants 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 COMPARATORParticipants 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 COMPARATORParticipants 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 COMPARATORParticipants 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 COMPARATORParticipants will be blinded and receive one dose (0.3mL) of BNT162b2 vaccine via intramuscular injection in the deltoid muscle.
Group 2b
ACTIVE COMPARATORParticipants will be blinded and receive one half dose (0.25mL) of mRNA-1273 vaccine via intramuscular injection in the deltoid muscle.
Group 3b
ACTIVE COMPARATORParticipants will be blinded and receive one half dose (0.25mL) of mRNA-1273 vaccine via intramuscular injection in the deltoid muscle.
Group 4b
ACTIVE COMPARATORParticipants will be blinded and receive one dose (0.3mL) of BNT162b2 vaccine via intramuscular injection in the deltoid muscle.
Group 5b
ACTIVE COMPARATORParticipants will be blinded and receive one half dose (0.25mL) of mRNA-1273 vaccine via intramuscular injection in the deltoid muscle.
Group 6b
ACTIVE COMPARATORParticipants will be blinded and receive one dose (0.3mL) of BNT162b2 vaccine via intramuscular injection in the deltoid muscle.
Group 7b
ACTIVE COMPARATORParticipants will be blinded and receive one dose (0.3mL) of BNT162b2 vaccine via intramuscular injection in the deltoid muscle.
Group 8b
ACTIVE COMPARATORParticipants will be blinded and receive one half dose (0.25mL) of mRNA-1273 vaccine via intramuscular injection in the deltoid muscle.
Group 9b
EXPERIMENTALParticipants will receive one dose (0.5mL) of Covifenz vaccine via intramuscular injection in the deltoid muscle.
Group 1c
ACTIVE COMPARATORParticipants will be blinded and receive one dose (0.3mL) of BNT162b2 vaccine via intramuscular injection in the deltoid muscle.
Group 2c
ACTIVE COMPARATORParticipants will be blinded and receive one dose (0.5mL) of Covifenz vaccine via intramuscular injection in the deltoid muscle.
Group 3c
ACTIVE COMPARATORParticipants will be blinded and receive one half dose (0.25mL) of mRNA-1273 vaccine via intramuscular injection in the deltoid muscle.
Group 4c
ACTIVE COMPARATORParticipants will be blinded and receive one dose (0.5mL) of Covifenz vaccine via intramuscular injection in the deltoid muscle.
Group 5c
ACTIVE COMPARATORParticipants 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 COMPARATORParticipants will be blinded and receive one dose (0.5mL) of Covifenz vaccine via intramuscular injection in the deltoid muscle.
Group 7c
EXPERIMENTALParticipants will receive one dose (0.5mL) of Covifenz vaccine via intramuscular injection in the deltoid muscle.
Interventions
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.
A white to off-white, sterile, preservative-free, frozen suspension for intramuscular injection, supplied with 0.9% sodium chloride diluent for injection plastic ampoules.
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).
Second injection administered 28 days post first injection
Second injection administered 112 days post first injection
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
Eligibility Criteria
You may qualify if:
- 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)
You may not qualify if:
- 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
- Administration of a live virus vaccine within 4 weeks prior to study vaccine receipt.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Canadian Immunization Research Networklead
- Canadian Center for Vaccinologycollaborator
- BC Children's Hospital Research Institutecollaborator
- Children's Hospital Research Institute of Manitobacollaborator
- CHU de Quebec-Universite Lavalcollaborator
- Ottawa Hospital Research Institutecollaborator
- Ontario Agency for Health Protection and Promotioncollaborator
- University of Torontocollaborator
- Massachusetts General Hospitalcollaborator
- Interior Healthcollaborator
- McGill University Health Centre/Research Institute of the McGill University Health Centrecollaborator
Study Sites (8)
Royal Inland Hospital
Kamloops, British Columbia, Canada
Penticton Regional Hospital
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
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Joanne Langley
Dalhousie University/CIRN
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
- Masking Details
- 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.
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- NETWORK
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 18, 2021
First Posted
May 20, 2021
Study Start
May 20, 2021
Primary Completion
November 15, 2024
Study Completion
August 1, 2025
Last Updated
March 18, 2025
Record last verified: 2025-03