SWITCH ON: Analysing the Immunogenicity of Additional Booster Vaccinations in HCW (SWITCHON)

SWITCH ON: Analysing the Immunogenicity of Additional Booster Vaccinations in Healthcare Workers. A Multicenter, Randomised, Controlled Trial

Eighty percent of the Dutch population has completed a primary COVID-19 vaccination regimen, and 60% of the population received a booster vaccination. Waning immunity, combined with the emergence of antigenically distinct SARS-CoV-2 variants, has led to the consideration of additional booster vaccinations in the Dutch population by autumn 2022. However, despite efforts of the Dutch policymakers, the public's willingness to repeatedly receive COVID-19 booster vaccinations is declining. This is mainly due to a reduced burden of disease by COVID-19, fewer hospitalizations, and fewer deaths. However, population immunity might be one of the major factors responsible for this reduced burden of disease, possibly emphasizing the need for booster vaccinations. In this proposal we will address an important question asked by policymakers: "Are booster vaccinations in autumn recommended for the healthy population?"

Study Overview

• Status: Active, not recruiting
• Conditions: Covid-19 Vaccination
• Intervention / Treatment: Drug: Direct boost mRNA; Drug: Direct boost adeno; Drug: Post-poned boost mRNA; Drug: Post-poned boost adeno

• Study Type: Interventional
• Enrollment (Actual): 431
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hugo van der Kuy, PharmD; Phone Number: +31628586702; Email: h.vanderkuy@erasmusmc.nl

Study Locations

• Netherlands
  • Amsterdam, Netherlands, 1105AZ
    • AmsterdamUMC
  • Groningen, Netherlands, 9713GZ
    • UMCG
  • Leiden, Netherlands, 2333ZA
    • LUMC
  • Rotterdam, Netherlands, 3015 GD
    • Erasmus MC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 67 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Participant is willing and able to give written informed consent for participation in the trial.
2. Adult (male/female) between 18 and 65 years old
3. Sufficient level of the Dutch language to undertake all study requirements

Exclusion Criteria:

1. Adults younger than 18 or older than 65 years.
2. Adults primed with another vaccine than Janssen, Moderna or Pfizer.
3. History of allergic reactions likely to be exacerbated by any component of study vaccines (e.g. hypersensitivity to the active substance or any of the SmPC-listed ingredients of the Janssen/Pfizer/Moderna vaccine).
4. Adults that are pregnant.
5. Currently being treated for cancer.
6. Severe kidney failure or dialyses dependent.
7. Status after organ-, stem cell- or bone marrow transplantation.
8. Use of immunosuppressant's.
9. Epilepsy.
10. HIV.
11. Bleeding disorder (e.g. factor deficiency, coagulopathy or platelet disorder), or prior history of significant bleeding of bruising following IM injections of vene puncture.
12. Continuous use of anticoagulants, such as coumarins (e.g. acenocoumarol) or novel oral anticoagulants (i.e. apixaban, dabigatran etc).
13. Participants who are currently participating in another research trial.
14. All regular contra-indications of the vaccines will be applied.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Direct boost mRNA; Participants will be randomised into a direct boost group (DB; i.e end of August) or a post-poned boost group (PPB; i.e 3-4 months later) group after stratification for priming (mRNA versus Janssen). The immune response will be measured at start of the study (visit 1, all participants) and 0, 7, 28 and 84 days after boost.	Drug: Direct boost mRNA; Participants will be boosted with a covid-19 vaccin after priming with mRNA
Active Comparator: Direct boost adeno; Participants will be randomised into a direct boost group (DB; i.e end of August) or a post-poned boost group (PPB; i.e 3-4 months later) group after stratification for priming (mRNA versus Janssen). The immune response will be measured at start of the study (visit 1, all participants) and 0, 7, 28 and 84 days after boost.	Drug: Direct boost adeno; Participants will be boosted with a covid-19 vaccin after priming with adeno
Active Comparator: Post-poned boost mRNA; Participants will be randomised into a direct boost group (DB; i.e end of August) or a post-poned boost group (PPB; i.e 3-4 months later) group after stratification for priming (mRNA versus Janssen). The immune response will be measured at start of the study (visit 1, all participants) and 0, 7, 28 and 84 days after boost.	Drug: Post-poned boost mRNA; Participants will be boosted with a covid-19 vaccin after priming with mRNA
Active Comparator: Post-poned boost adeno; Participants will be randomised into a direct boost group (DB; i.e end of August) or a post-poned boost group (PPB; i.e 3-4 months later) group after stratification for priming (mRNA versus Janssen). The immune response will be measured at start of the study (visit 1, all participants) and 0, 7, 28 and 84 days after boost.	Drug: Post-poned boost adeno; Participants will be boosted with a covid-19 vaccin after priming with adeno

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Is there an increase in antibody levels between day of boost and 28 days after boosting HCW that were initially primed with either the Janssen or an mRNA-based vaccine?	Outcome: Level and fold change of antibodies determined by a quantitative IgG assay comparing the Janssen primed and mRNA-based primed HCW.	28 days
Does booster vaccination lead to a rapid secondary recall response, indicative of immunological memory?	Outcome: Level and fold change of antibodies and T-cell responses determined by a quantitative IgG assay and whole blood IFNγ release assay, respectively, comparing day 7 and 28 post-boost.	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
What is the difference in booster immunogenicity comparing a direct boost with a postponed boost?	Outcome: Level of antibodies and T-cell responses 7 and 28 days post boost in DB versus PPB group.	28 days
What is the breadth of the immune responses after booster vaccination?	Outcome: PRNT against relevant variants in a random selection of study participants.	28 days
What is the predictive value of immune responses on day 7 post boost?	Outcome: Correlation between antibodies and T-cell responses on day 7 and 28 post boost in % of the 28 day response for both level of antibodies and T-cell responses	28 days
What is the difference in reactogenicity 7 days after boost comparing the Janssen and mRNA primed HCW?	Outcome: Adverse events (AE) first 7 days after an additional boost between Janssen and mRNA primed HCW.	7 days
Initial examination of breakthrough infections before and during study period	Outcome: Database of breakthrough infections in included participants based on positive PCR, self-reported positive lateral flow test, or detection of N-specific antibodies.	1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gene expression profiles associated with recall response (PAXgene tube)		28 days
SARS-CoV-2-specific T-cell responses	PBMC, assessed by activation-induced marker assay and / or TCRbeta sequencing	28 days

Collaborators and Investigators

• Sponsor: Erasmus Medical Center
• Collaborators: University Medical Center Groningen; Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA); Leiden University Medical Center; ZonMw: The Netherlands Organisation for Health Research and Development

Study record dates

Study Major Dates

• Study Start (Actual): August 20, 2022
• Primary Completion (Actual): September 15, 2022
• Study Completion (Anticipated): August 30, 2023

Study Registration Dates

• First Submitted: July 17, 2022
• First Submitted That Met QC Criteria: July 21, 2022
• First Posted (Actual): July 22, 2022

Study Record Updates

• Last Update Posted (Actual): February 15, 2023
• Last Update Submitted That Met QC Criteria: February 13, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Covid-19; Boost
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: MEC-2022-0462; 2022-002560-73 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All data will be shared upon a reasonable request to the PI of the study.
• IPD Sharing Time Frame: These data will become available 3 months after the start of the trial
• IPD Sharing Access Criteria: a reasonable request
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No