PREPARE-iVAC Trial

NCT05924685 | Completed Phase 4 DMC

• 2 other identifiers: 114422023-503894-39-00
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 7

Brief 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

Keywords

Kidney Transplant Recipients; COVID-19 vaccines; Everolimus; Mycophenolate Mofetil; Varicella Zoster Vaccine

Outcome Measures

Primary Outcomes (1)

• Virus-neutralizing capacity of SARS-CoV-2 antibodies

  The neutralizing antibody titer against the Omicron XBB.1.5 strain

  28 days after COVID-19 vaccination

Secondary Outcomes (7)

• SARS-CoV-2 antibody concentration

  28 days after COVID-19 vaccination

• SARS-CoV-2 specific T-cell response

  28 days after COVID-19 vaccination

• Varicella Zoster specific antibodies

  28 days after second Varicella Zoster vaccination

• Varicella Zoster specific T-cell Response

  28 days after second Varicella Zoster vaccination

• Solicited local and systemic adverse events

  Within 7 days after vaccination

Other Outcomes (4)

• Relationship between previous COVID-19 infection and immune responses

  28 days after vaccination

• Virus neutralizing capacity of SARS-CoV-2 antibodies

  28 days after COVID-19 vaccination

• Delayed SARS-CoV-2 antibody response

  56 days after COVID-19 vaccination

Study Arms (2)

Continue immunosuppressive therapy with MMF/MPA

ACTIVE COMPARATOR

Kidney transplant recipients with maintenance therapy, receiving the monovalent Omicron XBB.1.5 COVID-19 mRNA vaccine (Comirnaty, I.M.). Optional to receive the Recombinant Zoster Vaccine (Shingrix, I.M.).

Biological: COVID-19 vaccination

Replace immunosuppressive therapy with MMF/MPA by everolimus

ACTIVE COMPARATOR

Kidney transplant recipients replacing MMF/MPA by everolimus for at least six weeks, receiving the monovalent Omicron XBB.1.5 COVID-19 mRNA vaccine (Comirnaty, I.M.). Optional to receive the Recombinant Zoster Vaccine (Shingrix, I.M.).

Biological: COVID-19 vaccination

Interventions

COVID-19 vaccination BIOLOGICAL

Vaccination

Also known as: the monovalent Omicron XBB.1.5 COVID-19 mRNA vaccination

Continue immunosuppressive therapy with MMF/MPA; Replace immunosuppressive therapy with MMF/MPA by everolimus

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• ≥6 months after kidney transplantation
• Maintenance immunosuppressive therapy consisting of either triple or dual therapy including MMF/MPA with a minimum daily dose of 1000 mg (MMF) or 720 mg (MPA) and a CNI
• Eligible for the vaccinations as described by the instructions of the manufacturers of the vaccines (e.g. received 3 previous COVID-19 vaccinations as part of the primary COVID-19 immunisation)
• Capable of understanding the purpose and risks of the study, fully informed and given written informed consent (signed informed consent form has been obtained)
• Willing to adhere to the protocol and be available during the study period

You may not qualify if:

• Previous CNI trough levels not sufficient according to the discretion of the treating physician
• More than two previous kidney transplantations
• Calculated level of panel reactive antibodies prior to last transplantation above 85%
• Evidence of DSAs
• Signs of acute rejection during the preceding year
• Multi-organ transplant recipient
• History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (e.g. anaphylaxis) to any component of the study intervention(s)
• Contra-indications for use of everolimus according to the opinion of the treating physician
• Active COVID-19 disease
• Active malignancy, except non-melanoma skin cancer
• Inherited immune deficiency
• Infection with Human Immunodeficiency Virus (HIV)
• Administration of T-cell, B-cell, or plasma cell depleting antibodies during the last 6 months
• Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection
• Subjects with severe systemic infections, current or within the two weeks prior to randomisation

Sponsors & Collaborators

• University Medical Center Groningen: lead
• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): collaborator
• Radboud University Medical Center: collaborator
• Erasmus Medical Center: collaborator
• UMC Utrecht: collaborator
• Leiden University Medical Center: collaborator
• Maastricht University Medical Center: collaborator
• ZonMw: The Netherlands Organisation for Health Research and Development: collaborator
• Dutch Kidney Foundation: collaborator

Study Sites (7)

Radboud University Medical Center

Nijmegen, Gelderland, Netherlands

Location

Maastricht University Medical Center

Maastricht, Limburg, Netherlands

Location

Amsterdam University Medical Center

Amsterdam, North Holland, Netherlands

Location

Leiden University Medical Center

Leiden, South Holland, Netherlands

Location

Erasmus Medical Center

Rotterdam, South Holland, Netherlands

Location

University Medical Center Groningen

Groningen, Netherlands

Location

University Medical Center Utrecht

Utrecht, Netherlands

Location

MeSH Terms

Interventions

heterologous prime boost COVID-19 vaccination

Study Officials

• Jan-Stephan F Sanders, MD PhD

  University Medical Center Groningen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will be 1:1 randomised to: 1. Continue immunosuppressive therapy with MMF/MPA 2. Replace immunosuppressive therapy with MMF/MPA by everolimus

Study Record Dates

• First Submitted: June 20, 2023
• First Posted: June 29, 2023
• Study Start: August 22, 2023
• Primary Completion: December 29, 2023
• Study Completion: February 27, 2024
• Last Updated: March 4, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

NL (7)