Clinical trial NCT05343871: 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
Overall status: COMPLETED
Phase: PHASE4
Conditions: COVID-19
Keywords: Fractional dose
COVID-19
Lead sponsor: Albert B. Sabin Vaccine Institute
Sponsor class: OTHER
Collaborators: name: Aga Khan University
name: Oswaldo Cruz Foundation
name: Stanford University
First posted: 2022-04-25
Enrollment: 2354
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


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

Primary outcomes:
measure: Sero-response rate by Spike IgG binding ELISA at 28 days post booster
timeFrame: Day 28
measure: Safety and reactogenicity profile of fractional and full dose of study vaccines at 28 days post-booster vaccination
timeFrame: Day 28
Secondary outcomes:
measure: Sero-response rate by anti-Spike IgG binding ELISA at 3m and 6m post booster
timeFrame: Month 3 and Month 6
measure: Safety and reactogenicity profile of fractional and full dose of study vaccines throughout the trial
timeFrame: Throughout study, 6 months per participant
Other outcomes:
Locations:
city: Campo Grande
country: Brazil
facility: FIOCRUZ
state: MS Do Sul
city: Karachi
country: Pakistan
facility: Aga Khan University Clinical Trials Unit
state: Sindh
Study officials:
References: