PREPARE-iVAC Trial

Summary

Objective: To investigate whether replacement of MMF/MPA by everolimus in kidney transplant recipients results in superior immunogenicity of COVID-19 vaccination as measured by neutralizing antibody titer against the Omicron XBB.1.5 strain.

Trial design: Multicentre, open-label randomized controlled clinical trial, for a duration of at least 10 weeks with an optional extension to 18 weeks.

Trial population: Kidney transplant recipients, 18 years or older, who are at least 6 months after transplantation, with a functioning kidney transplant, using MMF/MPA in combination with at least one other immunosuppressant including a calcineurin inhibitor (CNI), with at least 3 previous COVID-19 vaccinations (=basic COVID-19 immunisation).

Interventions:

Patients will be randomized into one of two equally sized groups, with either continuation of their current immunosuppressive regimen including MMF/MPA or replacement of MMF/MPA by everolimus during at least six weeks before until four weeks after the last vaccination. Patients will receive a repeated COVID-19 vaccination with the monovalent Omicron XBB.1.5 vaccine, 28 days thereafter they can opt to also receive two herpes zoster vaccinations with the Recombinant Zoster Vaccine (RZV) with an interval between the first and second dose of 28 days.

Main trial endpoints:

The neutralizing antibody titer against the Omicron XBB.1.5. strain 28 days after monovalent Omicron XBB.1.5 COVID-19 vaccination in patients continuing MMF/MPA compared to patients who switched to everolimus.

Secondary trial endpoints:

* SARS-CoV-2 specific anti-S1 antibody level at 28 and 56 days after COVID-19 vaccination
* Varicella zoster specific anti-gE antibody level 28 days after 1st and 2nd herpes zoster vaccination
* SARS-CoV-2 specific T-cell response 28 days after COVID-19 vaccination
* Varicella zoster specific T-cell response 28 days after 2nd herpes zoster vaccination
* Safety in terms of incidence of acute rejection, kidney function decline, SAEs, AESIs and solicited local and systemic AEs after COVID-19 and herpes zoster vaccination

Conditions

• COVID-19 Vaccines
• Varicella Zoster Vaccine
• Vaccine Response
• Immunosuppression

Interventions

BIOLOGICAL

COVID-19 vaccination

Vaccination

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

  collaborator OTHER

• Radboud University Medical Center

  collaborator OTHER

• Erasmus Medical Center

  collaborator OTHER

• UMC Utrecht

  collaborator OTHER

• Leiden University Medical Center

  collaborator OTHER

• Maastricht University Medical Center

  collaborator OTHER

• ZonMw: The Netherlands Organisation for Health Research and Development

  collaborator OTHER

• Dutch Kidney Foundation

  collaborator OTHER

• University Medical Center Groningen

  lead OTHER

Principal Investigators

• Jan-Stephan F Sanders, MD PhD · University Medical Center Groningen

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-08-22

Primary Completion

2023-12-29

Completion

2024-02-27

Countries

• Netherlands

Study Locations