Mix and Match of the Second COVID-19 Vaccine Dose for Safety and Immunogenicity

Overview

The main goals of this study are to assess the immune response and safety of two different vaccines for first and second doses as well as for differing intervals between the first and second dose of two-dose vaccines.

Full Title of Study: “Immunogenicity and Adverse Events Following Immunization With Alternate Schedules of Authorized COVID-19 Vaccines in Canada: MOSAIC Study (Mix and Match of the Second cOvid-19 Vaccine Dose for SAfety and ImmunogeniCity)”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Prevention
    • Masking: Double (Participant, Outcomes Assessor)
  • Study Primary Completion Date: March 2023

Detailed Description

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.

Interventions

  • 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.
  • 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.
  • 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: 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

Arms, Groups and Cohorts

  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.

Clinical Trial Outcome Measures

Primary Measures

  • 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.

Secondary Measures

  • 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.

Participating in This Clinical Trial

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 second dose of study vaccine (Please refer to the definition section for a description of child-bearing potential and adequate contraception) 5. Vaccine-exposed subgroups: have received or are booked to receive the first dose of an authorized COVID-19 vaccine in the 57 days prior to Visit 1 (documentation of receipt required), OR 6. Vaccine naïve subgroups: have not received an authorized COVID-19 vaccine at any time 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. History of laboratory-confirmed COVID-19 disease prior to enrolment by participant report

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 99 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • Canadian Immunization Research Network
  • Collaborator
    • Canadian Center for Vaccinology
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Joanne Langley, Principal Investigator, Dalhousie University/CIRN
  • Overall Contact(s)
    • Melissa Holmes, 902-470-6854, melissa.holmes@dal.ca

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