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

COVID-19 Clinical Trial

— MOSAIC  

Official title:

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?

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04894435
• Other study ID #: CT24
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: May 20, 2021
• Est. completion date: May 2024

Study information

• Verified date: February 2024
• Source: Canadian Immunization Research Network
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 669
• Est. completion date: May 2024
• Est. primary completion date: March 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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.

Related Conditions & MeSH terms

• COVID-19

Intervention

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.
• 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.
• 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
• 0, 112 day schedule
Second injection administered 112 days post first injection

Biological:
• Covifenz
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

Locations

Country	Name	City	State
Canada	Canadian Center for Vaccinology	Halifax	Nova Scotia
Canada	Royal Inland Hospital	Kamloops	British Columbia
Canada	McGill University Health Centre Vaccine Study Centre	Montréal	Quebec
Canada	Ottawa Hospital Research Institute, University of Ottawa	Ottawa	Ontario
Canada	Penticton Regional Hospital	Penticton	British Columbia
Canada	CHU de Québec, Université Laval	Québec City	Quebec
Canada	BC Children's Hospital Research Institute	Vancouver	British Columbia
Canada	Children's Hospital Research Institute of Manitoba	Winnipeg	Manitoba

Sponsors (11)

Lead Sponsor

Collaborator

Canadian Immunization Research Network

BC Children's Hospital Research Institute, Canadian Center for Vaccinology, Children's Hospital Research Institute of Manitoba, CHU de Quebec-Universite Laval, Interior Health, Massachusetts General Hospital, McGill University Health Centre/Research Institute of the McGill University Health Centre, Ontario Agency for Health Protection and Promotion, Ottawa Hospital Research Institute, University of Toronto

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Exploratory assessment of interval between dose 1 and 2 on immune response after 3 or 4 doses	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.	From time of first study injection through Day 365.
Primary	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
Primary	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
Primary	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
Primary	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	Durability of antibody response to SARS-CoV-2 S over 12 months after 2 doses	Assess durability of immune responses in each study group over 12 months based on anti-spike antibody titers and pseudoneutralization assay.	Baseline and Days 28, 56, 112, 140, 365
Secondary	Pseudoneutralization assay, T cell testing, Antibody dependent cellular cytotoxicity (ADCC), Antibody avidity, RNA seq after 2 doses	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.	Days 28, 56, 112, 140, 365
Secondary	Incidence of grade 3 solicited local and systemic adverse events, SAEs, AEFIs, MAAEs, AESIs in the 7 days following vaccine receipt after 2 doses	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).	From time of first study injection through Day 365.
Secondary	Incidence of grade 3 solicited local and systemic adverse events, SAEs, AEFIs, MAAEs, AESIs in the 7 days following vaccine receipt after 3 doses	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).	From time of first study injection through Day 365.
Secondary	Acceptability of vaccines as determined by participant-completed questionnaire after 2 doses	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.	Days 56, 140, and 365
Secondary	Acceptability of vaccines as determined by participant-completed questionnaire after 3 doses	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.	Days 28, 180
Secondary	Antibody to SARS-CoV-2 S and N, RBD after 3 doses	Assess durability of the immune responses in each study group over 12 months after the study vaccine.	Days 180 and 365
Secondary	Pseudoneutralization assay, T cell testing, Antibody dependent cellular cytotoxicity after 3 doses	Further characterize the immune response to COVID-19 vaccine in schedules with homologous and heterologous third doses to day 365	Day 365
Secondary	Incidence of grade 3 solicited local and systemic adverse events, SAEs, AEFIs, MAAEs, AESIs in the 7 days following vaccine receipt after 4 doses	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).	From time of first study injection through Day 365.
Secondary	Acceptability of vaccines as determined by participant-completed questionnaire after 4 doses	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).	Days 28, 180
Secondary	Antibody to SARS-CoV-2 S and N, RBD after 4 doses	Assess durability of the immune responses in each study group over 12 months after the study vaccine.	Days 180 and 365
Secondary	Antibody dependent cellular cytotoxicity after 4 doses	Further characterize the immune response to COVID-19 vaccine in schedules with homologous and heterologous third doses to day 365	Day 365
Secondary	Pseudoneutralization assay after 4 doses	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	Day 365
Secondary	T cell testing after 4 doses	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	Day 365