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

NCT ID: NCT05343871

Last Updated: 2024-01-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 2354 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-07-05
• Study Completion Date: 2024-01-11

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.

Conditions

COVID-19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

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

Group Type: EXPERIMENTAL

AZD1222

Intervention Type: BIOLOGICAL

AstraZeneca ChAdOx1-S recombinant AZD1222 vaccine:

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

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

Group Type: ACTIVE_COMPARATOR

AZD1222

Intervention Type: BIOLOGICAL

AstraZeneca ChAdOx1-S recombinant AZD1222 vaccine:

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

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

Group Type: EXPERIMENTAL

BNT162b2

Intervention Type: BIOLOGICAL

Pfizer/BioNTech BNT162b2 mRNA vaccine:

• Full dose (30 micrograms)
• Half dose (15 micrograms)
• One-third dose (10 micrograms)

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

Group Type: EXPERIMENTAL

BNT162b2

Intervention Type: BIOLOGICAL

Pfizer/BioNTech BNT162b2 mRNA vaccine:

• Full dose (30 micrograms)
• Half dose (15 micrograms)
• One-third dose (10 micrograms)

Priming Group 1: Sinovac Prime, BNT162b2 full dose

Group Type: ACTIVE_COMPARATOR

BNT162b2

Intervention Type: BIOLOGICAL

Pfizer/BioNTech BNT162b2 mRNA vaccine:

• Full dose (30 micrograms)
• Half dose (15 micrograms)
• One-third dose (10 micrograms)

Priming Group 1: Sinovac Prime, Sinovac full dose

Group Type: ACTIVE_COMPARATOR

Sinovac

Intervention Type: BIOLOGICAL

Sinovac inactivated COVID-19 vaccine:

● Full dose (0.5 ml)

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

Group Type: EXPERIMENTAL

AZD1222

Intervention Type: BIOLOGICAL

AstraZeneca ChAdOx1-S recombinant AZD1222 vaccine:

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

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

Group Type: ACTIVE_COMPARATOR

AZD1222

Intervention Type: BIOLOGICAL

AstraZeneca ChAdOx1-S recombinant AZD1222 vaccine:

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

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

Group Type: EXPERIMENTAL

BNT162b2

Intervention Type: BIOLOGICAL

Pfizer/BioNTech BNT162b2 mRNA vaccine:

• Full dose (30 micrograms)
• Half dose (15 micrograms)
• One-third dose (10 micrograms)

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

Group Type: EXPERIMENTAL

BNT162b2

Intervention Type: BIOLOGICAL

Pfizer/BioNTech BNT162b2 mRNA vaccine:

• Full dose (30 micrograms)
• Half dose (15 micrograms)
• One-third dose (10 micrograms)

Priming Group 2: AZD1222 Prime, BNT162b2 full dose

Group Type: ACTIVE_COMPARATOR

BNT162b2

Intervention Type: BIOLOGICAL

Pfizer/BioNTech BNT162b2 mRNA vaccine:

• Full dose (30 micrograms)
• Half dose (15 micrograms)
• One-third dose (10 micrograms)

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

Group Type: EXPERIMENTAL

AZD1222

Intervention Type: BIOLOGICAL

AstraZeneca ChAdOx1-S recombinant AZD1222 vaccine:

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

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

Group Type: ACTIVE_COMPARATOR

AZD1222

Intervention Type: BIOLOGICAL

AstraZeneca ChAdOx1-S recombinant AZD1222 vaccine:

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

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

Group Type: EXPERIMENTAL

BNT162b2

Intervention Type: BIOLOGICAL

Pfizer/BioNTech BNT162b2 mRNA vaccine:

• Full dose (30 micrograms)
• Half dose (15 micrograms)
• One-third dose (10 micrograms)

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

Group Type: EXPERIMENTAL

BNT162b2

Intervention Type: BIOLOGICAL

Pfizer/BioNTech BNT162b2 mRNA vaccine:

• Full dose (30 micrograms)
• Half dose (15 micrograms)
• One-third dose (10 micrograms)

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

Group Type: ACTIVE_COMPARATOR

BNT162b2

Intervention Type: BIOLOGICAL

Pfizer/BioNTech BNT162b2 mRNA vaccine:

• Full dose (30 micrograms)
• Half dose (15 micrograms)
• One-third dose (10 micrograms)

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

Group Type: EXPERIMENTAL

BNT162b2

Intervention Type: BIOLOGICAL

Pfizer/BioNTech BNT162b2 mRNA vaccine:

• Full dose (30 micrograms)
• Half dose (15 micrograms)
• One-third dose (10 micrograms)

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

Group Type: EXPERIMENTAL

BNT162b2

Intervention Type: BIOLOGICAL

Pfizer/BioNTech BNT162b2 mRNA vaccine:

• Full dose (30 micrograms)
• Half dose (15 micrograms)
• One-third dose (10 micrograms)

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

Group Type: ACTIVE_COMPARATOR

BNT162b2

Intervention Type: BIOLOGICAL

Pfizer/BioNTech BNT162b2 mRNA vaccine:

• Full dose (30 micrograms)
• Half dose (15 micrograms)
• One-third dose (10 micrograms)

Interventions

Sinovac

Sinovac inactivated COVID-19 vaccine:

● Full dose (0.5 ml)

Intervention Type: BIOLOGICAL

AZD1222

AstraZeneca ChAdOx1-S recombinant AZD1222 vaccine:

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

Intervention Type: BIOLOGICAL

BNT162b2

Pfizer/BioNTech BNT162b2 mRNA vaccine:

• Full dose (30 micrograms)
• Half dose (15 micrograms)
• One-third dose (10 micrograms)

Intervention Type: BIOLOGICAL

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Aga Khan University

OTHER

Sponsor Role: collaborator

Oswaldo Cruz Foundation

OTHER

Sponsor Role: collaborator

Stanford University

OTHER

Sponsor Role: collaborator

Albert B. Sabin Vaccine Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

FIOCRUZ

Campo Grande, MS Do Sul, Brazil

Aga Khan University Clinical Trials Unit

Karachi, Sindh, Pakistan

Countries

Brazil; Pakistan

References

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.

Reference Type: DERIVED

PMID: 40620571 (View on PubMed)

Other Identifiers

Sabin CoV 22

Identifier Type: -

Identifier Source: org_study_id