Immunogenicity of Heterologous Versus Homologous Prime Boost Schedule With mRNA and Inactivated COVID-19 Vaccines

Study Overview
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Brief Summary
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This study is a randomized, simple-blinded comparative phase III clinical trial comparing the immunogenicity of two doses Coronovac to that of a first dose of Coronovac (Sinovac, Beijing, China) followed by a booster shot with the mRNA-based BNT162b2 SARS-CoV-2 vaccine (Comirnaty, Pfizer-BioNTech). The purpose of this study is to evaluate the superiority, safety and immunogenicity of the heterologous prime-boost CoronaVac/BNT162b2 vaccination to the homologous CoronaVac/CoronaVac regimen.

Detailed Description
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This study is a randomized simple-blinded comparative phase III clinical trial in COVID-19 vaccine naïve volunteers adults aged between 18 and 60 years. The purpose of this study is to evaluate the superiority, safety and immunogenicity of the heterologous prime-boost CoronaVac/BNT162b2 vaccination to the homologous CoronaVac/CoronaVac regimen. The study is conducted in four different sites located in the North of Tunisia. A total of 240 eligible participants were included. Among them, the primary end point data were available for 100 participants randomly allocated to heterologous boost group versus 99 participants randomly allocated to homologous boost dose group. Participants are assigned to receive either two injections of the CoronaVac vaccine (1st and 2nd vaccine), or CoronaVac as 1st dose and Pfizer as 2nd dose in 3 to 4 weeks interval. A blood sample (5ml of the whole blood) is collected for each participant at the vaccination center before the first dose injection. After verifying the absence of a SARS-CoV-2 infection during the interrogation (a follow-up survey), a 2nd blood sample (5ml of whole blood) is taken for each participant at the vaccination center before the second dose injection. After the two injections, a 3rd blood sample (5ml of whole blood) will be taken for each participant between day 21 and day 35 after the second dose. Data collection and all samples are treated at Institute Pasteur of Tunis.

Official Title
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Immunogenicity of Heterologous Versus Homologous Prime Boost Schedule With mRNA and Inactivated COVID-19 Vaccines: a Single-blinded, Randomized, Parallel Group Superiority Trial

Conditions
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COVID-19

Intervention / Treatment
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* Biological: CoronaVac/CoronaVac
* Biological: CoronaVac/BNT162b2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Acceptance to participate in the study. Age: 18-60 years old. Non-inclusion criteria: Presence of disability (mainly mental disability). Pregnancy. Patients under immunosuppressive treatment or immunocompromised individuals. Prior Covid-19 infection. Exclusion Criteria: Occurrence of a serious adverse event (death, anaphylactic shock, ...). Subjects wishing to withdraw from the study. Occurrence of a SARS-CoV-2 symptomatic infection during the follow-up period.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized simple-blinded comparative phase III clinical trial
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CoronaVac/CoronaVac<br>Biological: Coronavac Two doses at 21-day +/- 3 days. Each innoculation dose is 0.5 ml containing 600 SU in-house unit (equals to 3μg) of SARS-CoV-2 antigen. | Biological: CoronaVac/CoronaVac<br>* Two doses at 21-day +/- 3 days. Each innoculation dose is 0.5 ml containing 600 SU in-house unit (equals to 3μg) of SARS-CoV-2 antigen.<br>|
| Active Comparator: CoronaVac/BNT162b2<br>Biological: CoronaVac/BNT162b2 First dose of Coronavac. Each innoculation dose is 0.5 ml containing 600 SU in-house unit (equals to 3μg) of SARS-CoV-2 antigen. Second dose of BNT162b2 at 21-day +/- 3 days. Each dose of the Pfizer-BioNTech COVID-19 Vaccine is 0.3 ml. Each prefilled syringe contains 30 mcg of a nucleoside-modified messenger RNA (modRNA) encoding the viral spike (S) glycoprotein of SARS-CoV-2. | Biological: CoronaVac/BNT162b2<br>* First dose of Coronavac. Each innoculation dose is 0.5 ml containing 600 SU in-house unit (equals to 3μg) of SARS-CoV-2 antigen. Second dose of BNT162b2 at 21-day +/- 3 days. Each dose of the Pfizer-BioNTech COVID-19 Vaccine is 0.3 ml. Each prefilled syringe contains 30 mcg of a nucleoside-modified messenger RNA (modRNA) encoding the viral spike (S) glycoprotein of SARS-CoV-2<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Superiority of the heterologous prime-boost immunization with mRNA vaccine after vaccination with an inactivated vaccine versus homologous immunization with inactivated vaccines | The primary end point for immunogenicity was the serum neutralizing antibody level with a percentage of inhibition at 90% at 21-35 days after boost. A difference of 25% between groups was considered clinically relevant. | Between day 21 and day 35 after the second dose of vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunogenicity parameters (Neutralizing antibody and IgG antibody titers) between day 21 and day 35 | The level of neutralizing antibodies and anti-spike IgG antibody responses | Between day 21 and day 35 after the second dose of vaccination | 
| Immunogenicity parameters (Neutralizing antibody and IgG antibody titers) at day 0 (at baseline) | The level of neutralizing antibodies and anti-spike IgG antibody responses | At day 0 (at baseline) | 
| Immunogenicity parameters (Neutralizing antibody and IgG antibody titers) at day 21 +/- 3 days | The level of neutralizing antibodies and anti-spike IgG antibody responses | At day 21 +/- 3 days after the first dose of vaccination | 
| Safety indexes of adverse reactions at day 30 | The incidence of adverse reactions at day 30 of the second dose of vaccination | At day 30 after the second dose of vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vaccine, Immunogenicity, Heterologous prime-boost, Coronavac, Pfizer-BioNtech