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

Primary Purpose

COVID-19

Status
Recruiting
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Sinovac
AZD1222
BNT162b2
Sponsored by
Albert B. Sabin Vaccine Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for COVID-19 focused on measuring Fractional dose, COVID-19

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • FIOCRUZ
  • Aga Khan University Clinical Trials UnitRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm 11

Arm 12

Arm 13

Arm 14

Arm 15

Arm 16

Arm 17

Arm 18

Arm 19

Arm Type

Experimental

Active Comparator

Experimental

Experimental

Active Comparator

Active Comparator

Experimental

Active Comparator

Experimental

Experimental

Active Comparator

Experimental

Active Comparator

Experimental

Experimental

Active Comparator

Experimental

Experimental

Active Comparator

Arm Label

Priming Group 1: Sinovac Prime, AZD1222 ½ dose (Brazil only)

Priming Group 1: Sinovac Prime, AZD1222 full dose (Brazil only)

Priming Group 1: Sinovac Prime, BNT162b2 1/3 dose

Priming Group 1: Sinovac Prime, BNT162b2 1/2 dose

Priming Group 1: Sinovac Prime, BNT162b2 full dose

Priming Group 1: Sinovac Prime, Sinovac full dose

Priming Group 2: AZD1222 Prime, AZD1222 ½ dose (Brazil only)

Priming Group 2: AZD1222 Prime, AZD1222 full dose (Brazil only)

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

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

Priming Group 2: AZD1222 Prime, BNT162b2 full dose

Priming Group 3-B: BNT162b2 Prime, AZD1222 ½ dose (Brazil only)

Priming Group 3-B: BNT162b2 Prime, AZD1222 full dose (Brazil only)

Priming Group 3-B: BNT162b2 Prime, BNT162b2 1/3 dose (Brazil only)

Priming Group 3-B: BNT162b2 Prime, BNT162b2 1/2 dose (Brazil only)

Priming Group 3-B: BNT162b2 Prime, BNT162b2 full dose (Brazil only)

Priming Group 3-P: Natural Infection Prime, BNT162b2 1/3 dose (Pakistan only)

Priming Group 3-P: Natural Infection Prime, BNT162b2 1/2 dose (Pakistan only)

Priming Group 3-P: Natural Infection Prime, BNT162b2 full dose (Pakistan only)

Arm Description

Outcomes

Primary Outcome Measures

Sero-response rate by Spike IgG binding ELISA at 28 days post booster
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
Safety and reactogenicity profile of fractional and full dose of study vaccines at 28 days post-booster vaccination
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 Occurrence of solicited local and systemic reactions within 7 days of booster Occurrence of unsolicited AEs within 28 days of booster

Secondary Outcome Measures

Sero-response rate by anti-Spike IgG binding ELISA at 3m and 6m post booster
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
Safety and reactogenicity profile of fractional and full dose of study vaccines throughout the trial
Describe the safety and reactogenicity profile of fractional and full dose of study vaccines throughout the trial Occurrence of Medically attended adverse reactions within 3 months of booster 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

Full Information

First Posted
April 20, 2022
Last Updated
January 30, 2023
Sponsor
Albert B. Sabin Vaccine Institute
Collaborators
Aga Khan University, Oswaldo Cruz Foundation, Stanford University
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1. Study Identification

Unique Protocol Identification Number
NCT05343871
Brief Title
Immunogenicity and Safety of Fractional Booster Dose of COVID-19 Vaccines Available for Use in Pakistan/Brazil: A Phase 4 Dose-optimizing Trial
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 5, 2022 (Actual)
Primary Completion Date
July 2023 (Anticipated)
Study Completion Date
December 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Albert B. Sabin Vaccine Institute
Collaborators
Aga Khan University, Oswaldo Cruz Foundation, Stanford University

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19
Keywords
Fractional dose, COVID-19

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
The study will be observer-blind. Participants, data collectors (e.g., Investigator), and data evaluators (e.g., trial statisticians) are blinded. Only the staff involved in vaccine delivery will be unblinded and aware of which vaccine the participant is receiving (group allocation). Study staff who collect information on symptoms and adverse events, laboratory staff and statisticians conducting the analysis will all be blinded to the vaccine and dosage received.
Allocation
Randomized
Enrollment
2340 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Priming Group 1: Sinovac Prime, AZD1222 ½ dose (Brazil only)
Arm Type
Experimental
Arm Title
Priming Group 1: Sinovac Prime, AZD1222 full dose (Brazil only)
Arm Type
Active Comparator
Arm Title
Priming Group 1: Sinovac Prime, BNT162b2 1/3 dose
Arm Type
Experimental
Arm Title
Priming Group 1: Sinovac Prime, BNT162b2 1/2 dose
Arm Type
Experimental
Arm Title
Priming Group 1: Sinovac Prime, BNT162b2 full dose
Arm Type
Active Comparator
Arm Title
Priming Group 1: Sinovac Prime, Sinovac full dose
Arm Type
Active Comparator
Arm Title
Priming Group 2: AZD1222 Prime, AZD1222 ½ dose (Brazil only)
Arm Type
Experimental
Arm Title
Priming Group 2: AZD1222 Prime, AZD1222 full dose (Brazil only)
Arm Type
Active Comparator
Arm Title
Priming Group 2: AZD1222 Prime, BNT162b2 1/3 dose
Arm Type
Experimental
Arm Title
Priming Group 2: AZD1222 Prime, BNT162b2 1/2 dose
Arm Type
Experimental
Arm Title
Priming Group 2: AZD1222 Prime, BNT162b2 full dose
Arm Type
Active Comparator
Arm Title
Priming Group 3-B: BNT162b2 Prime, AZD1222 ½ dose (Brazil only)
Arm Type
Experimental
Arm Title
Priming Group 3-B: BNT162b2 Prime, AZD1222 full dose (Brazil only)
Arm Type
Active Comparator
Arm Title
Priming Group 3-B: BNT162b2 Prime, BNT162b2 1/3 dose (Brazil only)
Arm Type
Experimental
Arm Title
Priming Group 3-B: BNT162b2 Prime, BNT162b2 1/2 dose (Brazil only)
Arm Type
Experimental
Arm Title
Priming Group 3-B: BNT162b2 Prime, BNT162b2 full dose (Brazil only)
Arm Type
Active Comparator
Arm Title
Priming Group 3-P: Natural Infection Prime, BNT162b2 1/3 dose (Pakistan only)
Arm Type
Experimental
Arm Title
Priming Group 3-P: Natural Infection Prime, BNT162b2 1/2 dose (Pakistan only)
Arm Type
Experimental
Arm Title
Priming Group 3-P: Natural Infection Prime, BNT162b2 full dose (Pakistan only)
Arm Type
Active Comparator
Intervention Type
Biological
Intervention Name(s)
Sinovac
Intervention Description
Sinovac inactivated COVID-19 vaccine: ● Full dose (0.5 ml)
Intervention Type
Biological
Intervention Name(s)
AZD1222
Intervention Description
AstraZeneca ChAdOx1-S recombinant AZD1222 vaccine: Full dose (0.5 ml) Half dose (0.25 ml)
Intervention Type
Biological
Intervention Name(s)
BNT162b2
Intervention Description
Pfizer/BioNTech BNT162b2 mRNA vaccine: Full dose (30 micrograms) Half dose (15 micrograms) One-third dose (10 micrograms)
Primary Outcome Measure Information:
Title
Sero-response rate by Spike IgG binding ELISA at 28 days post booster
Description
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
Time Frame
Day 28
Title
Safety and reactogenicity profile of fractional and full dose of study vaccines at 28 days post-booster vaccination
Description
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 Occurrence of solicited local and systemic reactions within 7 days of booster Occurrence of unsolicited AEs within 28 days of booster
Time Frame
Day 28
Secondary Outcome Measure Information:
Title
Sero-response rate by anti-Spike IgG binding ELISA at 3m and 6m post booster
Description
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
Time Frame
Month 3 and Month 6
Title
Safety and reactogenicity profile of fractional and full dose of study vaccines throughout the trial
Description
Describe the safety and reactogenicity profile of fractional and full dose of study vaccines throughout the trial Occurrence of Medically attended adverse reactions within 3 months of booster 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
Time Frame
Throughout study, 6 months per participant

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Denise Garrett, MD
Phone
+1 202 842 5025
Email
sabin@sabin.org
Facility Information:
Facility Name
FIOCRUZ
City
Campo Grande
State/Province
MS Do Sul
Country
Brazil
Individual Site Status
Completed
Facility Name
Aga Khan University Clinical Trials Unit
City
Karachi
State/Province
Sindh
Country
Pakistan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Farah Qamar

12. IPD Sharing Statement

Learn more about this trial

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

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