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Trial record 1 of 2 for:    COVID | MOSAIC
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Mix and Match of the COVID-19 Vaccine for Safety and Immunogenicity (MOSAIC)

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ClinicalTrials.gov Identifier: NCT04894435
Recruitment Status : Recruiting
First Posted : May 20, 2021
Last Update Posted : March 8, 2022
Sponsor:
Collaborators:
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
Information provided by (Responsible Party):
Canadian Immunization Research Network

Tracking Information
First Submitted Date  ICMJE May 18, 2021
First Posted Date  ICMJE May 20, 2021
Last Update Posted Date March 8, 2022
Actual Study Start Date  ICMJE May 20, 2021
Estimated Primary Completion Date March 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 24, 2021)
  • Antibody response to SARS-CoV-2 S protein after 2 doses [ Time Frame: 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 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.
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: May 19, 2021)
  • Antibody response to SARS-CoV-2 S protein [ Time Frame: 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 [ 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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 24, 2021)
  • Durability of antibody response to SARS-CoV-2 S over 12 months after 2 doses [ Time Frame: 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 [ Time Frame: 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.
  • Incidence of grade 3 solicited local and systemic adverse events, SAEs, AEFIs, MAAEs, AESIs in the 7 days following vaccine receipt after 2 doses [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.
  • Antibody to SARS-CoV-2 S and N, RBD after 3 doses [ Time Frame: 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 [ Time Frame: Day 365 ]
    Further characterize the immune response to COVID-19 vaccine in schedules with homologous and heterologous third doses to day 365
Original Secondary Outcome Measures  ICMJE
 (submitted: May 19, 2021)
  • Durability of antibody response to SARS-CoV-2 S over 12 months [ Time Frame: 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 [ Time Frame: 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.
  • Incidence of grade 3 solicited local and systemic adverse events, SAEs, AEFIs, MAAEs, AESIs in the 7 days following vaccine receipt. [ Time Frame: 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. [ Time Frame: 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.
Current Other Pre-specified Outcome Measures
 (submitted: December 24, 2021)
Exploratory assessment of interval between dose 1 and 2 on immune response after 3 doses [ Time Frame: 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.
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Mix and Match of the COVID-19 Vaccine for Safety and Immunogenicity
Official Title  ICMJE 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 Third Dose (MOSAIC-2;CT24b) Safe and Immunogenic?
Brief Summary The main goals of this study are to assess the immune response and safety of two different vaccines for first, second, and third 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) are anticipated to be administered 6 months apart. We will assess the immunogenicity of both heterogeneous and heterologous third doses using the Canadian schedule.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

M = Moderna mRNA; P = Pfizer/BioNTech mRNA; A = AstraZeneca

MOSAIC 1:

  • Group 1 - M and M - 28 days apart
  • Group 2 - M and M - 112 days apart
  • Group 3 - M and P - 28 days apart
  • Group 4 - M and P - 112 days apart
  • Group 5 - P and P - 28 days apart
  • Group 6 - P and P - 112 days apart
  • Group 7 - P and M - 28 days apart
  • Group 8 - P and M - 112 days apart
  • Group 9 - A and M - 28 days apart
  • Group 10 - A and M - 112 days apart
  • Group 11 - A and P - 28 days apart
  • Group 12 - A and P - 112 days apart

MOSAIC 2:

  • Group 1b - P and P - followed by P
  • Group 2b - P and P - followed by M
  • Group 3b - M and M - followed by M
  • Group 4b - M and M - followed by P
  • Group 5b - P and M in any order - followed by M
  • Group 6b - P and M in any order - followed by P
  • Group 7b - A and P or M - followed by P
  • Group 8b - A and P or M - followed by M
Masking: Double (Participant, Outcomes Assessor)
Masking Description:
Participants, laboratory staff, and statistical analysis personnel will be blinded to which vaccine they are receiving.
Primary Purpose: Prevention
Condition  ICMJE COVID-19
Intervention  ICMJE
  • Biological: mRNA-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.
    Other Names:
    • COVID-19 Vaccine Moderna
    • Spikevax
  • Biological: BNT162b2
    A white to off-white, sterile, preservative-free, frozen suspension for intramuscular injection, supplied with 0.9% sodium chloride diluent for injection plastic ampoules.
    Other Names:
    • Pfizer-BioNTech COVID-19 Vaccine
    • Comirnaty
  • Biological: ChAdOx1-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).
    Other Names:
    • Astra Zeneca COVID-19 Vaccine
    • COVISHIELD AstraZeneca COVID-19 Vaccine
    • Vaxzevria
  • Other: 0, 28 day schedule
    Second injection administered 28 days post first injection
  • Other: 0, 112 day schedule
    Second injection administered 112 days post first injection
Study Arms  ICMJE
  • Active Comparator: 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.

    Interventions:
    • Biological: mRNA-1273 SARS-CoV-2 vaccine
    • Other: 0, 28 day schedule
  • Active Comparator: 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.

    Interventions:
    • Biological: mRNA-1273 SARS-CoV-2 vaccine
    • Other: 0, 112 day schedule
  • Active Comparator: 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.

    Interventions:
    • Biological: mRNA-1273 SARS-CoV-2 vaccine
    • Biological: BNT162b2
    • Other: 0, 28 day schedule
  • Active Comparator: 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.

    Interventions:
    • Biological: mRNA-1273 SARS-CoV-2 vaccine
    • Biological: BNT162b2
    • Other: 0, 112 day schedule
  • Active Comparator: 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.

    Interventions:
    • Biological: BNT162b2
    • Other: 0, 28 day schedule
  • Active Comparator: 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.

    Interventions:
    • Biological: BNT162b2
    • Other: 0, 112 day schedule
  • Active Comparator: 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.

    Interventions:
    • Biological: mRNA-1273 SARS-CoV-2 vaccine
    • Biological: BNT162b2
    • Other: 0, 28 day schedule
  • Active Comparator: 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.

    Interventions:
    • Biological: mRNA-1273 SARS-CoV-2 vaccine
    • Biological: BNT162b2
    • Other: 0, 112 day schedule
  • Active Comparator: 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.

    Interventions:
    • Biological: mRNA-1273 SARS-CoV-2 vaccine
    • Biological: ChAdOx1-S [recombinant]
    • Other: 0, 28 day schedule
  • Active Comparator: 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.

    Interventions:
    • Biological: mRNA-1273 SARS-CoV-2 vaccine
    • Biological: ChAdOx1-S [recombinant]
    • Other: 0, 112 day schedule
  • Active Comparator: 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.

    Interventions:
    • Biological: BNT162b2
    • Biological: ChAdOx1-S [recombinant]
    • Other: 0, 28 day schedule
  • Active Comparator: 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.

    Interventions:
    • Biological: BNT162b2
    • Biological: ChAdOx1-S [recombinant]
    • Other: 0, 112 day schedule
  • Active Comparator: Group 1b
    Participants will be blinded and receive one dose (0.3mL) of BNT162b2 vaccine via intramuscular injection in the deltoid muscle.
    Intervention: Biological: BNT162b2
  • Active Comparator: 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: Biological: mRNA-1273 SARS-CoV-2 vaccine
  • Active Comparator: 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: Biological: mRNA-1273 SARS-CoV-2 vaccine
  • Active Comparator: Group 4b
    Participants will be blinded and receive one dose (0.3mL) of BNT162b2 vaccine via intramuscular injection in the deltoid muscle.
    Intervention: Biological: BNT162b2
  • Active Comparator: 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: Biological: mRNA-1273 SARS-CoV-2 vaccine
  • Active Comparator: Group 6b
    Participants will be blinded and receive one dose (0.3mL) of BNT162b2 vaccine via intramuscular injection in the deltoid muscle.
    Intervention: Biological: BNT162b2
  • Active Comparator: Group 7b
    Participants will be blinded and receive one dose (0.3mL) of BNT162b2 vaccine via intramuscular injection in the deltoid muscle.
    Intervention: Biological: BNT162b2
  • Active Comparator: 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: Biological: mRNA-1273 SARS-CoV-2 vaccine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 24, 2021)
1060
Original Estimated Enrollment  ICMJE
 (submitted: May 19, 2021)
1300
Estimated Study Completion Date  ICMJE April 2023
Estimated Primary Completion Date March 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 99 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Melissa Holmes 902-470-6854 melissa.holmes@dal.ca
Contact: Jill Mutch, RN 902-470-3860 jill.mutch@iwk.nshealth.ca
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04894435
Other Study ID Numbers  ICMJE CT24
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Canadian Immunization Research Network
Study Sponsor  ICMJE Canadian Immunization Research Network
Collaborators  ICMJE
  • 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
Investigators  ICMJE
Principal Investigator: Joanne Langley Dalhousie University/CIRN
PRS Account Canadian Immunization Research Network
Verification Date December 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP