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

Phase 2
Completed
Conditions
COVID-19 VACCINE
COVID-19 Infection
Interventions
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
Registration Number
NCT05049226
Lead Sponsor
Mahidol University
Brief Summary

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

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).

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
1250
Inclusion Criteria
  1. Adult male or female age equal or more than 20 years with Thai ID cards
  2. 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
  3. Has provided written informed consent prior to performance of any study-specific procedure
  4. No history of fever or PUI symptoms within 7 days
Exclusion Criteria
  1. Any confirmed or suspected immunosuppressive or immunodeficient state.
  2. Contraindication to AZ or PF according to labelling of the products
  3. History of COVID infection within 3 months period
  4. Pregnancy

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Two doses of SV at interval 120 to 180 daysAstraZeneca ChAdOx1 AZD1222 vaccine (AZ) full doseParticipants who have received two doses of SV at interval 120 to 180 days
Two doses of SV at interval 60 to less than 90 daysAstraZeneca ChAdOx1 AZD1222 vaccine (AZ) full doseParticipants who have received two doses of SV at interval 60 to less than 90 days
Two doses of SV at interval 60 to less than 90 daysPfizer/BioNTech BNT162b2 vaccine (PF) half doseParticipants who have received two doses of SV at interval 60 to less than 90 days
Two doses of SV at interval 60 to less than 90 daysPfizer/BioNTech BNT162b2 vaccine (PF) full doseParticipants who have received two doses of SV at interval 60 to less than 90 days
Two doses of SV at interval 90 to less than 120 daysAstraZeneca ChAdOx1 AZD1222 vaccine (AZ) half doseParticipants who have received two doses of SV at interval 90 to less than 120 days
Two doses of SV at interval 90 to less than 120 daysPfizer/BioNTech BNT162b2 vaccine (PF) half doseParticipants who have received two doses of SV at interval 90 to less than 120 days
Two doses of SV at interval 60 to less than 90 daysAstraZeneca ChAdOx1 AZD1222 vaccine (AZ) half doseParticipants who have received two doses of SV at interval 60 to less than 90 days
Two doses of SV at interval 90 to less than 120 daysAstraZeneca ChAdOx1 AZD1222 vaccine (AZ) full doseParticipants who have received two doses of SV at interval 90 to less than 120 days
Two doses of SV at interval 90 to less than 120 daysPfizer/BioNTech BNT162b2 vaccine (PF) full doseParticipants who have received two doses of SV at interval 90 to less than 120 days
Two doses of SV at interval 120 to 180 daysAstraZeneca ChAdOx1 AZD1222 vaccine (AZ) half doseParticipants who have received two doses of SV at interval 120 to 180 days
Two doses of SV at interval 120 to 180 daysPfizer/BioNTech BNT162b2 vaccine (PF) half doseParticipants who have received two doses of SV at interval 120 to 180 days
Two doses of SV at interval 120 to 180 daysPfizer/BioNTech BNT162b2 vaccine (PF) full doseParticipants who have received two doses of SV at interval 120 to 180 days
Primary Outcome Measures
NameTimeMethod
GMT Anti-S IgG at baseline and after vaccinationDay 0, Day 28, Day 60 and Day 90

GMT Anti-S IgG at baseline and after vaccination at day 28, day 60 and day 90

GMFR changed from baseline in anti-S IgG GMT after vaccinationDay 28, Day 60 and Day 90

GMFR changed from baseline in anti-S IgG GMT at 28,60 and 90 days after vaccination

Anti-S IgG Seroresponses changed from baseline after vaccinationDay 28, Day 60 and Day 90

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

GMFR changed from baseline in NT50 against SARS-CoV-2 pseudovirus after vaccinationDay 28 and Day 90

GMFR changed from baseline in NT50 against SARS-CoV-2 pseudovirus at 28 and 90 days vaccination

Frequency of solicited reportable local adverse event after vaccinationDay 0 through Day 7

Frequency and percentage of solicited reportable local adverse events (pain or tenderness, erythema, swelling or induration) of vaccination

Frequency of solicited reportable systemic adverse event after vaccinationDay 0 through Day 7

Frequency and percentage of solicited reportable systemic adverse events (fever, headache, fatigue or malaise, myalgia, arthralgia, nausea or vomitting) of vaccination

Frequency of all unsolicited AEsDay 0 through Day 28

Frequency and percentage of all unsolicited AEs

Frequency of SAEsDay 0 through Day 90

Frequency and percentage of SAEs throughout the entire study period

GMT against SARS-Cov-2 pseudovirus (PVNT) Neutralizing antibody titer 50 at baseline and after vaccinationDay 0, Day 28 and Day 90

GMT against SARS-Cov-2 pseudovirus (PVNT) Neutralizing antibody titer 50 at baseline and after vaccination at day 28 and day 90

Secondary Outcome Measures
NameTimeMethod
NT50 seroresponses against SARS-CoV-2 using micro NT changed from baseline at 28 and 90 days after vaccination among those positive by PVNT assayDay 28 and Day 90

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

NT50 GMT against SARS-Cov-2 by micro neutralization assay at baseline and day 28 and day 90 after vaccinationDay 0, Day 28 and Day 90

NT50 GMT against SARS-Cov-2 by micro neutralization assay at baseline and day 28 and 90 after vaccination

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 assayDay 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

Trial Locations

Locations (7)

Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi hospital, Mahidol University

🇹🇭

Bang Phli, Samut Prakan, Thailand

Faculty of Medicine, Chiang Mai University

🇹🇭

Chiang Mai, Thailand

Faculty of Medicine, Khon Kaen University

🇹🇭

Khon Kaen, Thailand

Faculty of Medicine Siriraj Hospital, Mahidol University

🇹🇭

Bangkok Noi, Bangkok, Thailand

Faculty of Medicine Chulalongkorn University

🇹🇭

Pathum Wan, Bangkok, Thailand

Faculty of Medicine Thammasat University

🇹🇭

Khlong Luang, Pathum Thani, Thailand

Faculty of Medicine, Prince of Songkla University

🇹🇭

Hat Yai, Songkla, Thailand

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