Mix and Match COVID-19 Vaccines for Coronavirus Safety and Immunity

(MOSAIC Trial)

Recruiting at 7 trial locations

Overseen By Melissa Holmes

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Canadian Immunization Research Network

Must not be taking: Immunosuppressants, Anticoagulants

Disqualifiers: Cancer, Bleeding disorder, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

669 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on immunosuppressant medication or continuous anticoagulants, you may not be eligible to participate.

What data supports the effectiveness of the treatment BNT162b2, ChAdOx1-S [recombinant], Covifenz, mRNA-1273 SARS-CoV-2 vaccine?

Research shows that using different COVID-19 vaccines together, like ChAdOx1-S and BNT162b2 or mRNA-1273, can lead to stronger immune responses compared to using the same vaccine for both doses. This approach may also help overcome vaccine shortages and improve protection against the virus. ^{1 2 3 4 5}

Is it safe to mix and match COVID-19 vaccines like ChAdOx1-S, BNT162b2, and mRNA-1273?

Mixing COVID-19 vaccines like ChAdOx1-S, BNT162b2, and mRNA-1273 has been generally safe, with no serious adverse events reported in studies. Some mild side effects may occur, but these are similar to those seen with standard vaccine schedules. ^{1 2 4 6 7}

How is the Mix and Match COVID-19 Vaccines treatment different from other COVID-19 vaccine treatments?

The Mix and Match COVID-19 Vaccines treatment is unique because it uses a combination of different vaccine types, such as adenoviral vector vaccines (like ChAdOx1-S) and mRNA vaccines (like BNT162b2 and mRNA-1273), to potentially enhance immune response and address vaccine shortages. This approach, known as heterologous vaccination, may lead to stronger immunity compared to using the same vaccine type for all doses. ^{1 3 4 8 9}

What is the purpose of this trial?

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.

Research Team

Joanne Langley

Principal Investigator

Dalhousie University/CIRN

Eligibility Criteria

This trial is for adults over 18 who've had at least two COVID-19 vaccine doses ≥6 months ago, or are unvaccinated. They must be in good health or with stable conditions and not planning pregnancy soon. Those previously vaccinated can join if they're scheduled for their first dose within 55 days before the study.

Inclusion Criteria

I am willing and able to follow all study procedures for the entire study period.

I have never received a COVID-19 vaccine.

I have received or am scheduled for a COVID-19 vaccine within 55 days before Visit 1.

Exclusion Criteria

I am on a continuous anticoagulant medication.

I am unable or unwilling to give consent for the trial.

I am currently being treated for cancer, except for skin cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose 1 and 2 Administration

Participants receive the first and second doses of the COVID-19 vaccine, with intervals of either 28 days or 112 days between doses.

4-16 weeks

2 visits (in-person)

Dose 3 Administration

Participants receive the third dose of the COVID-19 vaccine, anticipated to be administered 6 months after the second dose.

6 months

1 visit (in-person)

Dose 4 Administration

Participants receive the fourth dose of the COVID-19 vaccine, anticipated to be administered 3 months after the third dose.

3 months

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the vaccination schedule, with assessments of immune response and adverse events.

12 months

Multiple visits (in-person and virtual)

Treatment Details

Interventions

• BNT162b2
• ChAdOx1-S [recombinant]
• Covifenz
• mRNA-1273 SARS-CoV-2 vaccine

Trial Overview The study tests immune response and safety of mixing different COVID-19 vaccines (Covifenz, mRNA-1273, BNT162b2, ChAdOx1-S) across four doses and various intervals between initial shots to see how well they work together.

Participant Groups

Group I: Group 9b Experimental Treatment 1 Intervention

Participants will receive one dose (0.5mL) of Covifenz vaccine via intramuscular injection in the deltoid muscle.

Group II: Group 7c Experimental Treatment 1 Intervention

Participants will receive one dose (0.5mL) of Covifenz vaccine via intramuscular injection in the deltoid muscle.

Group III: Group 2b Active Control 1 Intervention

Participants will be blinded and receive one half dose (0.25mL) of mRNA-1273 vaccine via intramuscular injection in the deltoid muscle.

Group IV: Group 8b Active Control 1 Intervention

Participants will be blinded and receive one half dose (0.25mL) of mRNA-1273 vaccine via intramuscular injection in the deltoid muscle.

Group V: Group 7: Pfizer/BioNTech, Moderna - 28 days apart Active Control 3 Interventions

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.

Group VI: Group 5: Pfizer/BioNTech, Pfizer/BioNTech - 28 days apart Active Control 2 Interventions

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.

Group VII: Group 7b Active Control 1 Intervention

Participants will be blinded and receive one dose (0.3mL) of BNT162b2 vaccine via intramuscular injection in the deltoid muscle.

Group VIII: Group 1b Active Control 1 Intervention

Participants will be blinded and receive one dose (0.3mL) of BNT162b2 vaccine via intramuscular injection in the deltoid muscle.

Group IX: Group 11: Astra Zeneca, Pfizer/BioNTech - 28 days apart Active Control 3 Interventions

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.

Group X: Group 12: Astra Zeneca, Pfizer/BioNTech - 112 days apart Active Control 3 Interventions

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.

Group XI: Group 9: Astra Zeneca, Moderna - 28 days apart Active Control 3 Interventions

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.

Group XII: Group 3: Moderna, Pfizer/BioNTech - 28 days apart Active Control 3 Interventions

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.

Group XIII: Group 3b Active Control 1 Intervention

Participants will be blinded and receive one half dose (0.25mL) of mRNA-1273 vaccine via intramuscular injection in the deltoid muscle.

Group XIV: Group 4: Moderna, Pfizer/BioNTech - 112 days apart Active Control 3 Interventions

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.

Group XV: Group 6: Pfizer/BioNTech, Pfizer/BioNTech - 112 days apart Active Control 2 Interventions

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.

Group XVI: Group 8: Pfizer/BioNTech, Moderna - 112 days apart Active Control 3 Interventions

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.

Group XVII: Group 10: Astra Zeneca, Moderna - 112 days apart Active Control 3 Interventions

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.

Group XVIII: Group 4b Active Control 1 Intervention

Participants will be blinded and receive one dose (0.3mL) of BNT162b2 vaccine via intramuscular injection in the deltoid muscle.

Group XIX: Group 5b Active Control 1 Intervention

Participants will be blinded and receive one half dose (0.25mL) of mRNA-1273 vaccine via intramuscular injection in the deltoid muscle.

Group XX: Group 6b Active Control 1 Intervention

Participants will be blinded and receive one dose (0.3mL) of BNT162b2 vaccine via intramuscular injection in the deltoid muscle.

Group XXI: Group 1: Moderna, Moderna - 28 Days apart Active Control 2 Interventions

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.

Group XXII: Group 2: Moderna, Moderna - 112 days apart Active Control 2 Interventions

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.

Group XXIII: Group 1c Active Control 1 Intervention

Participants will be blinded and receive one dose (0.3mL) of BNT162b2 vaccine via intramuscular injection in the deltoid muscle.

Group XXIV: Group 2c Active Control 1 Intervention

Participants will be blinded and receive one dose (0.5mL) of Covifenz vaccine via intramuscular injection in the deltoid muscle.

Group XXV: Group 3c Active Control 1 Intervention

Participants will be blinded and receive one half dose (0.25mL) of mRNA-1273 vaccine via intramuscular injection in the deltoid muscle.

Group XXVI: Group 4c Active Control 1 Intervention

Participants will be blinded and receive one dose (0.5mL) of Covifenz vaccine via intramuscular injection in the deltoid muscle.

Group XXVII: Group 5c Active Control 2 Interventions

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.

Group XXVIII: Group 6c Active Control 1 Intervention

Participants will be blinded and receive one dose (0.5mL) of Covifenz vaccine via intramuscular injection in the deltoid muscle.

Who Is Running the Clinical Trial?

Canadian Immunization Research Network

Lead Sponsor

Trials

12

Recruited

10,600+

Children's Hospital Research Institute of Manitoba

Collaborator

Trials

9

Recruited

3,400+

CHU de Quebec-Universite Laval

Collaborator

Trials

177

Recruited

110,000+

Ottawa Hospital Research Institute

Collaborator

Trials

585

Recruited

3,283,000+

Ontario Agency for Health Protection and Promotion

Collaborator

Trials

11

Recruited

28,800+

University of Toronto

Collaborator

Trials

739

Recruited

1,125,000+

Massachusetts General Hospital

Collaborator

Trials

3,066

Recruited

13,430,000+

Interior Health

Industry Sponsor

Trials

7

Recruited

701,000+

Canadian Center for Vaccinology

Collaborator

Trials

12

Recruited

6,300+

BC Children's Hospital Research Institute

Collaborator

Trials

14

Recruited

2,800+

References

1. England pubmed.ncbi.nlm.nih.gov

Safety of heterologous primary and booster schedules with ChAdOx1-S and BNT162b2 or mRNA-1273 vaccines: nationwide cohort study. [2023]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Evaluation of Post-Vaccination Symptoms of Two Common COVID-19 Vaccines Used in Abha, Aseer Region, Kingdom of Saudi Arabia. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Immunogenicity and safety of heterologous versus homologous prime-boost schedules with an adenoviral vectored and mRNA COVID-19 vaccine: a systematic review. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

The Effects of Heterologous Immunization with Prime-Boost COVID-19 Vaccination against SARS-CoV-2. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Immunogenicity and efficacy of heterologous ChAdOx1-BNT162b2 vaccination. [2022]

6. Netherlands pubmed.ncbi.nlm.nih.gov

COVID-19 vaccine associated demyelination & its association with MOG antibody. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Adverse reactions and production of neutralizing anti-SARS-CoV-2 antibodies after ChAdOx1 COVID-19 vaccination: A cross-sectional study in a single center. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Immunogenicity and reactogenicity of heterologous immunization against SARS CoV-2 using Sputnik V, ChAdOx1-S, BBIBP-CorV, Ad5-nCoV, and mRNA-1273. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of heterologous versus homologous prime-boost schedules with an adenoviral vectored and mRNA COVID-19 vaccine (Com-COV): a single-blind, randomised, non-inferiority trial. [2023]