Immunogenicity and Safety of Fractional Booster Dose of COVID-19 Vaccines Available for Use in Pakistan/Brazil: A Phase 4 Dose-optimizing Trial

January 29, 2024 updated by: Albert B. Sabin Vaccine Institute

Randomized Controlled Trial to Assess the Immunogenicity and Safety of Full Versus Fractional Dose of Pfizer/BioNTech, AstraZeneca, and Sinovac COVID-19 Vaccines Given as a Booster Dose at Least 6 Months After Primary Vaccination Series or PCR-confirmed Infection With SARS-CoV-2 in Healthy Adults

Since the emergence of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogen in late 2019, millions of people around the world have fallen ill and died from coronavirus disease 2019 (COVID-19), with variant-fueled case spikes causing repeated cycles of morbidity and mortality. The rapid development and emergency use authorization of vaccines against SARS-CoV-2 presents an enormous opportunity to protect populations, but bottlenecks in production have led to demand for vaccines that far outpaces supply. This project will investigate the immunogenicity of fractional doses of SARS-CoV-2 vaccines given a minimum of six months following an initial two-dose schedule or following natural immunity via documented infection. The consortium of research partners from the Sabin Vaccine Institute, Aga Khan University, Fundação Oswaldo Cruz (Fiocruz), and Stanford University will recruit volunteers to receive a full or fractional booster dose of BNT162b2, AZD1222 or Sinovac following receipt of their primary vaccination series or PCR-confirmed natural infection in Pakistan. The research team will follow participants for six months from boosting, with blood draws at baseline, 28 days, 3 months and 6 months, and measure sero-response rate (SRR) by anti-Spike immunoglobulin G (IgG) binding enzyme-linked immunosorbent assay (ELISA) with the ultimate aim of identifying whether fractional doses provide a similar immune response compared to full doses of vaccine.

Study Overview

Status

Completed

Conditions

Study Type

Interventional

Enrollment (Actual)

2354

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Denise Garrett, MD
  • Phone Number: +1 202 842 5025
  • Email: sabin@sabin.org

Study Locations

    • MS Do Sul
      • Campo Grande, MS Do Sul, Brazil
        • FIOCRUZ
    • Sindh
      • Karachi, Sindh, Pakistan
        • Aga Khan University Clinical Trials Unit

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Healthy male or female individuals aged 18 years to 60 years
  • Participant is willing and able to give written informed consent for participation in the trial
  • Individuals who can comply with trial procedures and are available for the duration of follow-up.

Brazil:

● Previous vaccination with a complete primary series of Sinovac (Priming Group 1), AZD1222 (Priming Group 2), or BNT162b2 (Priming Group 3-B) at least 6 months prior to screening

Pakistan:

● Previous vaccination with a complete primary series of Sinovac (Priming Group 1) or AZD1222 (Priming Group 2) at least 6 months prior to screening, or PCR-confirmed natural infection (Priming Group 3-P) between February 2021 - 6 months prior to screening

Exclusion Criteria:

  • Has a contraindication to BNT162b2, AZD1222 or Sinovac
  • Has received an incomplete primary COVID-19 vaccination series
  • Has received 3 doses of COVID-19 vaccine
  • Has received heterologous primary COVID-19 vaccination series
  • History of a solid organ or bone marrow transplant
  • History of malignancy (other than non-melanoma skin cancer) within the past five years
  • Currently on hemodialysis
  • Any confirmed or suspected immunosuppressive or immunodeficiency condition or diagnosis
  • On chronic (>30 days) use of immunosuppressive medications at the time of enrollment (except topical steroids or short-term oral steroids, i.e., ≤14 days)
  • Known diagnosis of HIV with CD4 count <200 cells/mm3 (in the past 6 months)
  • Active or history of previous auto-immune neurological disorders (e.g., multiple sclerosis, Guillain-Barre syndrome, transverse myelitis) (excluding Bell's palsy)
  • Has received anti-CD20 monoclonal antibodies for any reason in the past 12 months
  • Has received monoclonal antibodies to treat a previous COVID-19 event
  • Pregnant at screening
  • Positive SARS-CoV-2 Antigen test in respiratory specimen at screening
  • Planning to migrate out of the study area within 6 months of the enrollment
  • Participants currently enrolled in any other COVID-19 vaccine research trial in which they are getting a COVID-19 vaccine during the study period
  • Illiterate individuals (Brazil only)
  • Has a severe and/or uncontrolled comorbidity

Pakistan (natural infection Priming Group (Priming Group 3-P)):

● Prior vaccination with ANY vaccine against COVID-19

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Priming Group 1: Sinovac Prime, BNT162b2 1/3 dose

Pfizer/BioNTech BNT162b2 mRNA vaccine:

  • Full dose (30 micrograms)
  • Half dose (15 micrograms)
  • One-third dose (10 micrograms)
Experimental: Priming Group 1: Sinovac Prime, BNT162b2 1/2 dose

Pfizer/BioNTech BNT162b2 mRNA vaccine:

  • Full dose (30 micrograms)
  • Half dose (15 micrograms)
  • One-third dose (10 micrograms)
Active Comparator: Priming Group 1: Sinovac Prime, BNT162b2 full dose

Pfizer/BioNTech BNT162b2 mRNA vaccine:

  • Full dose (30 micrograms)
  • Half dose (15 micrograms)
  • One-third dose (10 micrograms)
Active Comparator: Priming Group 1: Sinovac Prime, Sinovac full dose

Sinovac inactivated COVID-19 vaccine:

● Full dose (0.5 ml)

Experimental: Priming Group 2: AZD1222 Prime, BNT162b2 1/3 dose

Pfizer/BioNTech BNT162b2 mRNA vaccine:

  • Full dose (30 micrograms)
  • Half dose (15 micrograms)
  • One-third dose (10 micrograms)
Experimental: Priming Group 2: AZD1222 Prime, BNT162b2 1/2 dose

Pfizer/BioNTech BNT162b2 mRNA vaccine:

  • Full dose (30 micrograms)
  • Half dose (15 micrograms)
  • One-third dose (10 micrograms)
Active Comparator: Priming Group 2: AZD1222 Prime, BNT162b2 full dose

Pfizer/BioNTech BNT162b2 mRNA vaccine:

  • Full dose (30 micrograms)
  • Half dose (15 micrograms)
  • One-third dose (10 micrograms)
Experimental: Priming Group 3-B: BNT162b2 Prime, AZD1222 ½ dose (Brazil only)

AstraZeneca ChAdOx1-S recombinant AZD1222 vaccine:

  • Full dose (0.5 ml)
  • Half dose (0.25 ml)
Active Comparator: Priming Group 3-B: BNT162b2 Prime, AZD1222 full dose (Brazil only)

AstraZeneca ChAdOx1-S recombinant AZD1222 vaccine:

  • Full dose (0.5 ml)
  • Half dose (0.25 ml)
Experimental: Priming Group 3-B: BNT162b2 Prime, BNT162b2 1/3 dose (Brazil only)

Pfizer/BioNTech BNT162b2 mRNA vaccine:

  • Full dose (30 micrograms)
  • Half dose (15 micrograms)
  • One-third dose (10 micrograms)
Experimental: Priming Group 3-B: BNT162b2 Prime, BNT162b2 1/2 dose (Brazil only)

Pfizer/BioNTech BNT162b2 mRNA vaccine:

  • Full dose (30 micrograms)
  • Half dose (15 micrograms)
  • One-third dose (10 micrograms)
Active Comparator: Priming Group 3-B: BNT162b2 Prime, BNT162b2 full dose (Brazil only)

Pfizer/BioNTech BNT162b2 mRNA vaccine:

  • Full dose (30 micrograms)
  • Half dose (15 micrograms)
  • One-third dose (10 micrograms)
Experimental: Priming Group 3-P: Natural Infection Prime, BNT162b2 1/3 dose (Pakistan only)

Pfizer/BioNTech BNT162b2 mRNA vaccine:

  • Full dose (30 micrograms)
  • Half dose (15 micrograms)
  • One-third dose (10 micrograms)
Experimental: Priming Group 3-P: Natural Infection Prime, BNT162b2 1/2 dose (Pakistan only)

Pfizer/BioNTech BNT162b2 mRNA vaccine:

  • Full dose (30 micrograms)
  • Half dose (15 micrograms)
  • One-third dose (10 micrograms)
Active Comparator: Priming Group 3-P: Natural Infection Prime, BNT162b2 full dose (Pakistan only)

Pfizer/BioNTech BNT162b2 mRNA vaccine:

  • Full dose (30 micrograms)
  • Half dose (15 micrograms)
  • One-third dose (10 micrograms)
Experimental: Priming Group 1: Sinovac Prime, AZD1222 ½ dose (Brazil only)

AstraZeneca ChAdOx1-S recombinant AZD1222 vaccine:

  • Full dose (0.5 ml)
  • Half dose (0.25 ml)
Active Comparator: Priming Group 1: Sinovac Prime, AZD1222 full dose (Brazil only)

AstraZeneca ChAdOx1-S recombinant AZD1222 vaccine:

  • Full dose (0.5 ml)
  • Half dose (0.25 ml)
Experimental: Priming Group 2: AZD1222 Prime, AZD1222 ½ dose (Brazil only)

AstraZeneca ChAdOx1-S recombinant AZD1222 vaccine:

  • Full dose (0.5 ml)
  • Half dose (0.25 ml)
Active Comparator: Priming Group 2: AZD1222 Prime, AZD1222 full dose (Brazil only)

AstraZeneca ChAdOx1-S recombinant AZD1222 vaccine:

  • Full dose (0.5 ml)
  • Half dose (0.25 ml)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Sero-response rate by Spike IgG binding ELISA at 28 days post booster
Time Frame: Day 28
Assess and compare humoral immune response from a fractional vs. full booster dose of BNT162b2 or AZD1222 in immunocompetent adults fully primed with BNT162b2, AZD1222, or Sinovac vaccines or natural infection, measured by anti-Spike IgG binding ELISA at 28 days post booster
Day 28
Safety and reactogenicity profile of fractional and full dose of study vaccines at 28 days post-booster vaccination
Time Frame: Day 28

Describe the safety and reactogenicity profile of fractional and full dose of study vaccines at 28 days post-booster vaccination through estimated incidence of solicited local and systemic adverse events, and incidence of unsolicited reported adverse events

  1. Occurrence of solicited local and systemic reactions within 7 days of booster
  2. Occurrence of unsolicited AEs within 28 days of booster
Day 28

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Sero-response rate by anti-Spike IgG binding ELISA at 3m and 6m post booster
Time Frame: Month 3 and Month 6
Assess the persistence of humoral immunity after a fractional vs. full booster dose of BNT162b2 or AZD1222 in immunocompetent adults fully primed with BNT162b2, AZD1222, or Sinovac vaccines or natural infection, measured by anti-Spike IgG binding ELISA at 3m and 6m post booster
Month 3 and Month 6
Safety and reactogenicity profile of fractional and full dose of study vaccines throughout the trial
Time Frame: Throughout study, 6 months per participant

Describe the safety and reactogenicity profile of fractional and full dose of study vaccines throughout the trial

  1. Occurrence of Medically attended adverse reactions within 3 months of booster
  2. Occurrence of adverse events (AE), Serious adverse events (SAE), and adverse events of special interest (AESI) within 28 days, 3 months, and 6 months of booster
Throughout study, 6 months per participant

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 5, 2022

Primary Completion (Actual)

July 28, 2023

Study Completion (Actual)

January 11, 2024

Study Registration Dates

First Submitted

April 20, 2022

First Submitted That Met QC Criteria

April 22, 2022

First Posted (Actual)

April 25, 2022

Study Record Updates

Last Update Posted (Actual)

January 30, 2024

Last Update Submitted That Met QC Criteria

January 29, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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