Immunogenicity and Safety of Fractional Booster Dose of COVID-19 Vaccines Available for Use in Pakistan/Brazil: A Phase 4 Dose-optimizing Trial
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
1 other identifier
interventional
2,354
2 countries
2
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_4 covid19
Started Jul 2022
Typical duration for phase_4 covid19
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 20, 2022
CompletedFirst Posted
Study publicly available on registry
April 25, 2022
CompletedStudy Start
First participant enrolled
July 5, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 28, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
January 11, 2024
CompletedJanuary 30, 2024
January 1, 2024
1.1 years
April 20, 2022
January 29, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
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
Day 28
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 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 Outcomes (2)
Sero-response rate 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
Throughout study, 6 months per participant
Study Arms (19)
Priming Group 1: Sinovac Prime, AZD1222 ½ dose (Brazil only)
EXPERIMENTALPriming Group 1: Sinovac Prime, AZD1222 full dose (Brazil only)
ACTIVE COMPARATORPriming Group 1: Sinovac Prime, BNT162b2 1/3 dose
EXPERIMENTALPriming Group 1: Sinovac Prime, BNT162b2 1/2 dose
EXPERIMENTALPriming Group 1: Sinovac Prime, BNT162b2 full dose
ACTIVE COMPARATORPriming Group 1: Sinovac Prime, Sinovac full dose
ACTIVE COMPARATORPriming Group 2: AZD1222 Prime, AZD1222 ½ dose (Brazil only)
EXPERIMENTALPriming Group 2: AZD1222 Prime, AZD1222 full dose (Brazil only)
ACTIVE COMPARATORPriming Group 2: AZD1222 Prime, BNT162b2 1/3 dose
EXPERIMENTALPriming Group 2: AZD1222 Prime, BNT162b2 1/2 dose
EXPERIMENTALPriming Group 2: AZD1222 Prime, BNT162b2 full dose
ACTIVE COMPARATORPriming Group 3-B: BNT162b2 Prime, AZD1222 ½ dose (Brazil only)
EXPERIMENTALPriming Group 3-B: BNT162b2 Prime, AZD1222 full dose (Brazil only)
ACTIVE COMPARATORPriming Group 3-B: BNT162b2 Prime, BNT162b2 1/3 dose (Brazil only)
EXPERIMENTALPriming Group 3-B: BNT162b2 Prime, BNT162b2 1/2 dose (Brazil only)
EXPERIMENTALPriming Group 3-B: BNT162b2 Prime, BNT162b2 full dose (Brazil only)
ACTIVE COMPARATORPriming Group 3-P: Natural Infection Prime, BNT162b2 1/3 dose (Pakistan only)
EXPERIMENTALPriming Group 3-P: Natural Infection Prime, BNT162b2 1/2 dose (Pakistan only)
EXPERIMENTALPriming Group 3-P: Natural Infection Prime, BNT162b2 full dose (Pakistan only)
ACTIVE COMPARATORInterventions
Sinovac inactivated COVID-19 vaccine: ● Full dose (0.5 ml)
AstraZeneca ChAdOx1-S recombinant AZD1222 vaccine: * Full dose (0.5 ml) * Half dose (0.25 ml)
Pfizer/BioNTech BNT162b2 mRNA vaccine: * Full dose (30 micrograms) * Half dose (15 micrograms) * One-third dose (10 micrograms)
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
- +6 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Albert B. Sabin Vaccine Institutelead
- Aga Khan Universitycollaborator
- Oswaldo Cruz Foundationcollaborator
- Stanford Universitycollaborator
Study Sites (2)
FIOCRUZ
Campo Grande, MS Do Sul, Brazil
Aga Khan University Clinical Trials Unit
Karachi, Sindh, Pakistan
Related Publications (1)
Barros Verruck J, Moreira Puga MA, de Oliveira RD, Vieira da Silva P, Charu V, Hedlin H, Lu D, Zhang A, Ritter V, Shaw B, Rosser JI, Seidman JC, Carter AS, Qamar F, Luby S, Garret D, Croda J. Antispike IgG antibody decay after immunisation with fractional versus full booster doses of COVID-19 vaccines: a 6-month longitudinal analysis of the FRACT-COV trial in Brazil. BMJ Public Health. 2025 Jul 5;3(2):e002331. doi: 10.1136/bmjph-2024-002331. eCollection 2025.
PMID: 40620571DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Masking Details
- 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.
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 20, 2022
First Posted
April 25, 2022
Study Start
July 5, 2022
Primary Completion
July 28, 2023
Study Completion
January 11, 2024
Last Updated
January 30, 2024
Record last verified: 2024-01