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

Phase 2Active Not RecruitingNCT04894435

Canadian Immunization Research Network669 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

TRIPLE

Enrollment

669

Conditions

COVID-19

Interventions

mRNA-1273 SARS-CoV-2 vaccineBIOLOGICAL

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.

BNT162b2BIOLOGICAL

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]BIOLOGICAL

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).

Eligibility

Sex: ALLMin age: 18 YearsMax age: 99 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Locations (8)

Royal Inland Hospital

Kamloops, British Columbia, Canada

Penticton Regional Hospital

Penticton, British Columbia, Canada

BC Children's Hospital Research Institute

Vancouver, British Columbia, Canada

Children's Hospital Research Institute of Manitoba

Winnipeg, Manitoba, Canada

Outcomes

Primary Outcomes

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.

Time frame: Day 56

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.

Time frame: Day 140

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.

Time frame: Day 28

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.

Time frame: Day 28

Secondary Outcomes

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.

Time frame: Baseline and Days 28, 56, 112, 140, 365

Pseudoneutralization assay, T cell testing, Antibody dependent cellular cytotoxicity (ADCC), Antibody avidity, RNA seq after 2 doses

Data from ClinicalTrials.gov

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