Third Dose Vaccination With AstraZeneca or Pfizer COVID-19 Vaccine Among Adults Received Sinovac COVID-19 Vaccine

Study Overview
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Brief Summary
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This prospective, multi-center, randomized, observer-blind Phase 2 study. A total of 1320 participants will be divided into 2 groups (660 each) receiving either full dose or half dose of either AZ or PF. Each group is further stratified into 3 subgroups according to three interval duration in term of days after second dose of SV for 60 to less than 90 days, 90 to less than120 days and 120 to 180 days. Each group will be randomized to receive either AZ or PF in 1:1 ratio. Subjects who fulfilled eligibility criteria will be randomly assigned to receive either full dose or half dose of AZ or PF in 1:1 ratio as an IM injection in the deltoid muscle at Visit 1 (V1). Subjects will be follow-up for assessing immunity at day 28 (V3), day 60 (V4) and day 90 (V5) and for safety at day 7 (V2), day 28 (V3), day 60 (V4) and day 90 (V5). At least 50% from each subgroup will be randomly selected to provide additional blood at baseline (V1, day 0) and day 28 (V3) to be used for assessment of T-cell-mediated immunity (CMI)

Detailed Description
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This study has been designed to assess immune response and safety of third dose vaccination with AstraZeneca ChAdOx1AZD1222 vaccine or Pfizer/BioNTech BNT162b2 vaccine among Thai subjects who have received two doses of Sinovac. The types of vaccines provided by the government included 7.7 million doses of inactivated vaccine manufactured by Sinovac and 6.5 million doses of AstraZeneca ChAdOx1 AZD1222 vaccine. With the limited supplies of COVID vaccines in many regions of the world especially in LMIC including Thailand and the evidences of waning immunity of especially inactivated vaccine have raised the concerns whether third dose is needed. The third dose that available now in Thailand are AstraZeneca ChAdOx1AZD1222 vaccine (AZ)/ Pfizer/BioNTech BNT162b2 vaccine (PF) and whether this can be provided with half dose so that the vaccination coverage is going to be higher in spite of limited vaccine supplies. A number of studies have proved that COVID-19 vaccines are effective at preventing people from getting severe COVID-19 disease. However, the vaccines do not only reduce the chance of infection, but they also help to mitigate disease severity. Study population: Male and female adults aged equal or more than 20 years who received two doses of Inactivated COVID-19 vaccine developed by Sinovac (given at 21-28 days apart) at different intervals of 60 to less than 90 days, 90 to less than120 days and 120 to 180 days This prospective, multi-center, randomized, observer-blind Phase 2 study, A total of 1320 participants will be divided into 2 groups (660 each) receiving either full dose or half dose of either AZ or PF. Each group is further stratified into 3 subgroups according to three interval duration in term of days after second dose of SV for 60-less than 90 days, 90-less than120 days and 120-180 days respectively. Subjects who fulfilled eligibility criteria will be randomly assigned to receive either full dose or half dose of AZ or PF in 1:1 ratio as an IM injection in the deltoid muscle at Visit 1 (V1). All participants will be randomized based on dose given either full dose or half dose and further stratify accordingly by Interactive web-based response system (IWRS). There will be unblinded team which consists of pharmacist and nurse who will give injection. All the safety assessment will be performed independently by clinical team. Subjects will be follow-up for assessing immunity at day 28 (V3), day 60 (V4) and day 90 (V5) and for safety at day 7 (V2), day 28 (V3), day 60 (V4) and day 90 (V5).

Official Title
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A Randomized, Observer-blind Trial to Assess the Immunogenicity and Safety of Third Dose Vaccination With AstraZeneca COVID-19 Vaccine or Pfizer/BioNTech COVID-19 Vaccine Among Thai Adults Receiving Two Doses of Sinovac

Conditions
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COVID-19 Infection, COVID-19 VACCINE

Intervention / Treatment
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* Biological: AstraZeneca ChAdOx1 AZD1222 vaccine (AZ) full dose
* Biological: Pfizer/BioNTech BNT162b2 vaccine (PF) full dose
* Biological: AstraZeneca ChAdOx1 AZD1222 vaccine (AZ) half dose
* Biological: Pfizer/BioNTech BNT162b2 vaccine (PF) half dose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult male or female age equal or more than 20 years with Thai ID cards Received two doses (21-28 days apart) of Sinovac inactivated COVID-19 vaccine who will be divided according to their intervals 60-less than 90 days, 90-less than120 days and 120-180 days Has provided written informed consent prior to performance of any study-specific procedure No history of fever or PUI symptoms within 7 days Exclusion Criteria: Any confirmed or suspected immunosuppressive or immunodeficient state. Contraindication to AZ or PF according to labelling of the products History of COVID infection within 3 months period Pregnancy

Ages Eligible for Study
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Minimum Age: 20 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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Two doses of SV at interval 60 to less than 90 days<br>Participants who have received two doses of SV at interval 60 to less than 90 days | Biological: AstraZeneca ChAdOx1 AZD1222 vaccine (AZ) full dose<br>* Astrazeneca COVID-19 (ChAdOx1 AZD1222) vaccine: One dose (0.5 ml) contains: COVID-19 Vaccine (ChAdOx1-S* recombinant) 5 × 10^10 viral particles (vp) *Recombinant, replication-deficient chimpanzee adenovirus vector encoding the SARS-CoV-2 Spike glycoprotein. Produced in genetically modified human embryonic kidney (HEK) 293 cells. Administer: Intramuscular (IM) injection in the deltoid muscle<br>Biological: Pfizer/BioNTech BNT162b2 vaccine (PF) full dose<br>* Pfizer-BioNTech COVID-19 (BNT162b2) vaccine: Diluent: 0.9% sodium chloride (normal saline, preservative-free) Administer: Intramuscular (IM) injection in the deltoid muscle<br>Biological: AstraZeneca ChAdOx1 AZD1222 vaccine (AZ) half dose<br>* Astrazeneca COVID-19 (ChAdOx1 AZD1222) vaccine: One dose (0.5 ml) contains: COVID-19 Vaccine (ChAdOx1-S* recombinant) 5 × 10^10 viral particles (vp) *Recombinant, replication-deficient chimpanzee adenovirus vector encoding the SARS-CoV-2 Spike glycoprotein. Produced in genetically modified human embryonic kidney (HEK) 293 cells. Administer: Intramuscular (IM) injection in the deltoid muscle<br>Biological: Pfizer/BioNTech BNT162b2 vaccine (PF) half dose<br>* Pfizer-BioNTech COVID-19 (BNT162b2) vaccine: Diluent: 0.9% sodium chloride (normal saline, preservative-free) Administer: Intramuscular (IM) injection in the deltoid muscle<br>|
| Experimental: Two doses of SV at interval 90 to less than 120 days<br>Participants who have received two doses of SV at interval 90 to less than 120 days | Biological: AstraZeneca ChAdOx1 AZD1222 vaccine (AZ) full dose<br>* Astrazeneca COVID-19 (ChAdOx1 AZD1222) vaccine: One dose (0.5 ml) contains: COVID-19 Vaccine (ChAdOx1-S* recombinant) 5 × 10^10 viral particles (vp) *Recombinant, replication-deficient chimpanzee adenovirus vector encoding the SARS-CoV-2 Spike glycoprotein. Produced in genetically modified human embryonic kidney (HEK) 293 cells. Administer: Intramuscular (IM) injection in the deltoid muscle<br>Biological: Pfizer/BioNTech BNT162b2 vaccine (PF) full dose<br>* Pfizer-BioNTech COVID-19 (BNT162b2) vaccine: Diluent: 0.9% sodium chloride (normal saline, preservative-free) Administer: Intramuscular (IM) injection in the deltoid muscle<br>Biological: AstraZeneca ChAdOx1 AZD1222 vaccine (AZ) half dose<br>* Astrazeneca COVID-19 (ChAdOx1 AZD1222) vaccine: One dose (0.5 ml) contains: COVID-19 Vaccine (ChAdOx1-S* recombinant) 5 × 10^10 viral particles (vp) *Recombinant, replication-deficient chimpanzee adenovirus vector encoding the SARS-CoV-2 Spike glycoprotein. Produced in genetically modified human embryonic kidney (HEK) 293 cells. Administer: Intramuscular (IM) injection in the deltoid muscle<br>Biological: Pfizer/BioNTech BNT162b2 vaccine (PF) half dose<br>* Pfizer-BioNTech COVID-19 (BNT162b2) vaccine: Diluent: 0.9% sodium chloride (normal saline, preservative-free) Administer: Intramuscular (IM) injection in the deltoid muscle<br>|
| Experimental: Two doses of SV at interval 120 to 180 days<br>Participants who have received two doses of SV at interval 120 to 180 days | Biological: AstraZeneca ChAdOx1 AZD1222 vaccine (AZ) full dose<br>* Astrazeneca COVID-19 (ChAdOx1 AZD1222) vaccine: One dose (0.5 ml) contains: COVID-19 Vaccine (ChAdOx1-S* recombinant) 5 × 10^10 viral particles (vp) *Recombinant, replication-deficient chimpanzee adenovirus vector encoding the SARS-CoV-2 Spike glycoprotein. Produced in genetically modified human embryonic kidney (HEK) 293 cells. Administer: Intramuscular (IM) injection in the deltoid muscle<br>Biological: Pfizer/BioNTech BNT162b2 vaccine (PF) full dose<br>* Pfizer-BioNTech COVID-19 (BNT162b2) vaccine: Diluent: 0.9% sodium chloride (normal saline, preservative-free) Administer: Intramuscular (IM) injection in the deltoid muscle<br>Biological: AstraZeneca ChAdOx1 AZD1222 vaccine (AZ) half dose<br>* Astrazeneca COVID-19 (ChAdOx1 AZD1222) vaccine: One dose (0.5 ml) contains: COVID-19 Vaccine (ChAdOx1-S* recombinant) 5 × 10^10 viral particles (vp) *Recombinant, replication-deficient chimpanzee adenovirus vector encoding the SARS-CoV-2 Spike glycoprotein. Produced in genetically modified human embryonic kidney (HEK) 293 cells. Administer: Intramuscular (IM) injection in the deltoid muscle<br>Biological: Pfizer/BioNTech BNT162b2 vaccine (PF) half dose<br>* Pfizer-BioNTech COVID-19 (BNT162b2) vaccine: Diluent: 0.9% sodium chloride (normal saline, preservative-free) Administer: Intramuscular (IM) injection in the deltoid muscle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| GMT Anti-S IgG at baseline and after vaccination | GMT Anti-S IgG at baseline and after vaccination at day 28, day 60 and day 90 | Day 0, Day 28, Day 60 and Day 90 | 
| GMFR changed from baseline in anti-S IgG GMT after vaccination | GMFR changed from baseline in anti-S IgG GMT at 28,60 and 90 days after vaccination | Day 28, Day 60 and Day 90 | 
| Anti-S IgG Seroresponses changed from baseline after vaccination | Frequency and percentage of participants with seroresponses in anti-S IgG titer as defined by (1) a ≥ 4-fold increase from baseline at 28, 60 and 90 days after vaccination (2) a ≥ 10-fold increase from baseline at 28,60 and 90 days after vaccination | Day 28, Day 60 and Day 90 | 
| GMT against SARS-Cov-2 pseudovirus (PVNT) Neutralizing antibody titer 50 at baseline and after vaccination | GMT against SARS-Cov-2 pseudovirus (PVNT) Neutralizing antibody titer 50 at baseline and after vaccination at day 28 and day 90 | Day 0, Day 28 and Day 90 | 
| GMFR changed from baseline in NT50 against SARS-CoV-2 pseudovirus after vaccination | GMFR changed from baseline in NT50 against SARS-CoV-2 pseudovirus at 28 and 90 days vaccination | Day 28 and Day 90 | 
| Frequency of solicited reportable local adverse event after vaccination | Frequency and percentage of solicited reportable local adverse events (pain or tenderness, erythema, swelling or induration) of vaccination | Day 0 through Day 7 | 
| Frequency of solicited reportable systemic adverse event after vaccination | Frequency and percentage of solicited reportable systemic adverse events (fever, headache, fatigue or malaise, myalgia, arthralgia, nausea or vomitting) of vaccination | Day 0 through Day 7 | 
| Frequency of all unsolicited AEs | Frequency and percentage of all unsolicited AEs | Day 0 through Day 28 | 
| Frequency of SAEs | Frequency and percentage of SAEs throughout the entire study period | Day 0 through Day 90 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| NT50 GMT against SARS-Cov-2 by micro neutralization assay at baseline and day 28 and day 90 after vaccination | NT50 GMT against SARS-Cov-2 by micro neutralization assay at baseline and day 28 and 90 after vaccination | Day 0, Day 28 and Day 90 | 
| GMFR changed from baseline in NT50 against SARS-CoV-2 (micro NT Delta/WT NA) at 28 and 90 days after vaccination among those positives by PNT assay | GMFR changed from baseline in NT50 against SARS-CoV-2 (micro NT Delta/WT NA) at 28 and 90 days after vaccination among those positives by PNT assay | Day 28 and Day 90 | 
| NT50 seroresponses against SARS-CoV-2 using micro NT changed from baseline at 28 and 90 days after vaccination among those positive by PVNT assay | Frequency and percentage of participants with NT50 seroresponses against SARS-CoV-2 using micro NT as defined by (1) a ≥ 4-fold increase from baseline at 28 and 90 days after vaccination compare to baseline among those positive by PVNT assay | Day 28 and Day 90 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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safety, COVID-19 Infection, COVID-19 Respiratory Infection, COVID-19 VACCINE, AstraZeneca COVID-19 VACCINE, AstraZeneca COVID-19 (ChAdOx1 AZD1222) vaccine, Pfizer/BioNTech COVID-19 VACCINE, Pfizer/BioNTech COVID-19 (BNT162b2) vaccine, Thai adults, full dose AstraZeneca COVID-19 VACCINE, half dose AstraZeneca COVID-19 VACCINE, full dose Pfizer/BioNTech COVID-19 VACCINE, half dose Pfizer/BioNTech COVID-19 VACCINE, Sinovac COVID-19 Vaccine, immunogenicity