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

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

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)

Study Overview

• Status: Completed
• Conditions: COVID-19 Infection; COVID-19 VACCINE
• Intervention / Treatment: 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

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).

• Study Type: Interventional
• Enrollment (Actual): 1250
• Phase: Phase 2

Contacts and Locations

Study Locations

• Thailand
  • Chiang Mai, Thailand, 50200
    • Faculty of Medicine, Chiang Mai University
  • Khon Kaen, Thailand, 40002
    • Faculty of Medicine, Khon Kaen University
  • Bangkok
    • Bangkok Noi, Bangkok, Thailand, 10700
      • Faculty of Medicine Siriraj Hospital, Mahidol University
    • Pathum Wan, Bangkok, Thailand, 10330
      • Faculty of Medicine Chulalongkorn University
  • Pathum Thani
    • Khlong Luang, Pathum Thani, Thailand, 12121
      • Faculty of Medicine Thammasat University
  • Samut Prakan
    • Bang Phli, Samut Prakan, Thailand, 10540
      • Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi hospital, Mahidol University
  • Songkla
    • Hat Yai, Songkla, Thailand, 90110
      • Faculty of Medicine, Prince of Songkla University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Two doses of SV at interval 60 to less than 90 days; Participants who have received two doses of SV at interval 60 to less than 90 days	Biological: AstraZeneca ChAdOx1 AZD1222 vaccine (AZ) full dose; 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; Biological: Pfizer/BioNTech BNT162b2 vaccine (PF) full dose; Pfizer-BioNTech COVID-19 (BNT162b2) vaccine: Diluent: 0.9% sodium chloride (normal saline, preservative-free) Administer: Intramuscular (IM) injection in the deltoid muscle; Biological: AstraZeneca ChAdOx1 AZD1222 vaccine (AZ) half dose; 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; Biological: Pfizer/BioNTech BNT162b2 vaccine (PF) half dose; Pfizer-BioNTech COVID-19 (BNT162b2) vaccine: Diluent: 0.9% sodium chloride (normal saline, preservative-free) Administer: Intramuscular (IM) injection in the deltoid muscle
Experimental: Two doses of SV at interval 90 to less than 120 days; Participants who have received two doses of SV at interval 90 to less than 120 days	Biological: AstraZeneca ChAdOx1 AZD1222 vaccine (AZ) full dose; 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; Biological: Pfizer/BioNTech BNT162b2 vaccine (PF) full dose; Pfizer-BioNTech COVID-19 (BNT162b2) vaccine: Diluent: 0.9% sodium chloride (normal saline, preservative-free) Administer: Intramuscular (IM) injection in the deltoid muscle; Biological: AstraZeneca ChAdOx1 AZD1222 vaccine (AZ) half dose; 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; Biological: Pfizer/BioNTech BNT162b2 vaccine (PF) half dose; Pfizer-BioNTech COVID-19 (BNT162b2) vaccine: Diluent: 0.9% sodium chloride (normal saline, preservative-free) Administer: Intramuscular (IM) injection in the deltoid muscle
Experimental: Two doses of SV at interval 120 to 180 days; Participants who have received two doses of SV at interval 120 to 180 days	Biological: AstraZeneca ChAdOx1 AZD1222 vaccine (AZ) full dose; 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; Biological: Pfizer/BioNTech BNT162b2 vaccine (PF) full dose; Pfizer-BioNTech COVID-19 (BNT162b2) vaccine: Diluent: 0.9% sodium chloride (normal saline, preservative-free) Administer: Intramuscular (IM) injection in the deltoid muscle; Biological: AstraZeneca ChAdOx1 AZD1222 vaccine (AZ) half dose; 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; Biological: Pfizer/BioNTech BNT162b2 vaccine (PF) half dose; Pfizer-BioNTech COVID-19 (BNT162b2) vaccine: Diluent: 0.9% sodium chloride (normal saline, preservative-free) Administer: Intramuscular (IM) injection in the deltoid muscle

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
S protein-specific T cells response at baseline, 28 days after vaccination given at different intervals	Frequency and percentage of S protein-specific T cells response elicited by each of the regimens as measured by QuantiFERON at baseline and 28 days after vaccination	Day 28
Seroresponse against SARS-CoV-2 pseudovirus towards Omicron strains at baseline, 28 and 90 days after vaccination	Frequency and percentage of subjects with % inhibition response at 1:80 dilution against SARS-CoV-2 pseudovirus as defined by more than 50% and 68% inhibition towards Omicron strains	Day 0, 28 and 90
NT50 GMT against SARS-Cov-2 pseudovirus (pVNT) Omicrron strain at baseline 28 and 90 days after vaccination	NT50 GMT against SARS-Cov-2 pseudovirus (pVNT) Omicrron strain at baseline 28 and 90 days after vaccination	Day 0, 28 and 90
GMFR changed from baseline in NT50 against SARS-CoV-2 pseudovirus (pVNT), Omicron strain at 28 and 90 days after vaccination	GMFR changed from baseline in NT50 against SARS-CoV-2 pseudovirus (pVNT), Omicron strain at 28 and 90 days after vaccination	Day 28, 90

Collaborators and Investigators

• Sponsor: Mahidol University
• Collaborators: Clinixir Co., Ltd.; Program Management Unit-C (PMU-C), governed by Ministry of Higher Education, Science, Research and Innovation (MHESI)
• Investigators: Study Chair: Punnee Pitisuttithum, MD, Vaccine Trial Centre, Faculty of Tropical Medicine, Mahidol University; Principal Investigator: Atibordee Meesing, MD, Faculty of Medicine, Khon Kaen University; Principal Investigator: Romanee Chaiwarith, MD,MHS, Faculty of Medicine, Chiang Mai University; Principal Investigator: Sarunyou Chusri, MD,PhD, Faculty of Medicine, Prince of Songkla University; Principal Investigator: Sira Nanthapisal, MD,PhD, Faculty of Medicine, Thammasat University; Principal Investigator: Suppachok Kirdlarp, MD, Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi hospital,Mahidol University; Principal Investigator: Suvimol Niyomnaitham, MD,PhD, Mahidol University; Principal Investigator: Sarawut Siwamogsatham, MD, Chulalongkorn University

Study record dates

Study Major Dates

• Study Start (Actual): September 24, 2021
• Primary Completion (Actual): February 22, 2022
• Study Completion (Actual): February 22, 2022

Study Registration Dates

• First Submitted: September 14, 2021
• First Submitted That Met QC Criteria: September 16, 2021
• First Posted (Actual): September 20, 2021

Study Record Updates

• Last Update Posted (Actual): July 6, 2022
• Last Update Submitted That Met QC Criteria: July 3, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: safety; immunogenicity; 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
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Infections; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: TVTN001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: data or left over specimen will be shared for future study ONLY subject who consent allow using their data/specimens. Sharing will be done without personnel identification
• IPD Sharing Time Frame: 2 years
• IPD Sharing Access Criteria: as document attach when completed study in NCT clinicaltrials.gov
• IPD Sharing Supporting Information Type: Study Protocol

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No