Clinical trial NCT04894435: Mix and Match of the COVID-19 Vaccine for Safety and Immunogenicity
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?
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: COVID-19
Keywords: SARS-CoV-2
vaccine
clinical trial
Lead sponsor: Canadian Immunization Research Network
Sponsor class: NETWORK
Collaborators: name: Canadian Center for Vaccinology
name: BC Children's Hospital Research Institute
name: Children's Hospital Research Institute of Manitoba
name: CHU de Quebec-Universite Laval
name: Ottawa Hospital Research Institute
name: Ontario Agency for Health Protection and Promotion
name: University of Toronto
name: Massachusetts General Hospital
name: Interior Health
name: McGill University Health Centre/Research Institute of the McGill University Health Centre
First posted: 2021-05-20
Enrollment: 669
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: M=Moderna SpikeVax mRNA; P=Pfizer/BioNTech Comirnaty mRNA; A=AstraZeneca Vaxzervia; C=Medicago Covifenz VLP

MOSAIC 1:

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

MOSAIC 2:

* Group 1b - P, P, P
* Group 2b - P, P, M
* Group 3b - M, M, M
* Group 4b - M, M, P
* Group 5b - P and M in any order, M
* Group 6b - P and M in any order, P
* Group 7b - A, P or M, P
* Group 8b - A, P or M, M
* Group 9b - Any vaccine in any order, C (open-label)

MOSAIC 3:

* Group 1c - P, P, P, P
* Group 2c - P, P, P, C
* Group 3c - M, M, M, M
* Group 4c - M, M, M, C
* Group 5c - Any 3 in any order, P or M
* Group 6c - Any 3 in any order, C
* Group 7c - Any 3 in any order, C (open-label)
Primary purpose: PREVENTION

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.

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) 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Antibody response to SARS-CoV-2 S protein after 2 doses
timeFrame: Day 56
measure: Antibody response to SARS-CoV-2 S protein after 2 doses
timeFrame: Day 140
measure: Antibody response to SARS-CoV-2 S protein after 3 doses
timeFrame: Day 28
measure: Antibody response to SARS-CoV-2 S protein after 4 doses
timeFrame: Day 28
Secondary outcomes:
measure: Durability of antibody response to SARS-CoV-2 S over 12 months after 2 doses
timeFrame: Baseline and Days 28, 56, 112, 140, 365
measure: Pseudoneutralization assay, T cell testing, Antibody dependent cellular cytotoxicity (ADCC), Antibody avidity, RNA seq after 2 doses
timeFrame: Days 28, 56, 112, 140, 365
measure: Incidence of grade 3 solicited local and systemic adverse events, SAEs, AEFIs, MAAEs, AESIs in the 7 days following vaccine receipt after 2 doses
timeFrame: From time of first study injection through Day 365.
measure: Incidence of grade 3 solicited local and systemic adverse events, SAEs, AEFIs, MAAEs, AESIs in the 7 days following vaccine receipt after 3 doses
timeFrame: From time of first study injection through Day 365.
measure: Acceptability of vaccines as determined by participant-completed questionnaire after 2 doses
timeFrame: Days 56, 140, and 365
measure: Acceptability of vaccines as determined by participant-completed questionnaire after 3 doses
timeFrame: Days 28, 180
measure: Antibody to SARS-CoV-2 S and N, RBD after 3 doses
timeFrame: Days 180 and 365
measure: Pseudoneutralization assay, T cell testing, Antibody dependent cellular cytotoxicity after 3 doses
timeFrame: Day 365
measure: Incidence of grade 3 solicited local and systemic adverse events, SAEs, AEFIs, MAAEs, AESIs in the 7 days following vaccine receipt after 4 doses
timeFrame: From time of first study injection through Day 365.
measure: Acceptability of vaccines as determined by participant-completed questionnaire after 4 doses
timeFrame: Days 28, 180
measure: Antibody to SARS-CoV-2 S and N, RBD after 4 doses
timeFrame: Days 180 and 365
measure: Antibody dependent cellular cytotoxicity after 4 doses
timeFrame: Day 365
measure: Pseudoneutralization assay after 4 doses
timeFrame: Day 365
measure: T cell testing after 4 doses
timeFrame: Day 365
Other outcomes:
measure: Exploratory assessment of interval between dose 1 and 2 on immune response after 3 or 4 doses
timeFrame: From time of first study injection through Day 365.
Locations:
city: Kamloops
country: Canada
facility: Royal Inland Hospital
state: British Columbia
city: Penticton
country: Canada
facility: Penticton Regional Hospital
state: British Columbia
city: Vancouver
country: Canada
facility: BC Children's Hospital Research Institute
state: British Columbia
city: Winnipeg
country: Canada
facility: Children's Hospital Research Institute of Manitoba
state: Manitoba
city: Halifax
country: Canada
facility: Canadian Center for Vaccinology
state: Nova Scotia
city: Ottawa
country: Canada
facility: Ottawa Hospital Research Institute, University of Ottawa
state: Ontario
city: Montréal
country: Canada
facility: McGill University Health Centre Vaccine Study Centre
state: Quebec
city: Québec City
country: Canada
facility: CHU de Québec, Université Laval
state: Quebec
Study officials:
affiliation: Dalhousie University/CIRN
name: Joanne Langley
role: PRINCIPAL_INVESTIGATOR
References: