RECOVAC Repeated Vaccination Study

Summary

Rationale: The humoral and cellular immune response after two mRNA vaccinations is severely attenuated in kidney transplant patients compared to controls, especially when their immunosuppressive regimen contains mycophenolate mofetil (MMF) / mycophenolic acid (MPA). A repeated dose strategy is therefore required to improve the efficacy of vaccination.

Objective: To investigate the immunogenicity of third or fourth dose SARS-CoV-2 vaccination strategies in kidney transplant patients.

Study design: Prospective, multicentre, open-label randomized clinical trial

Study population: Patients with a functioning kidney transplant who did not seroconvert after two or three doses of a mRNA vaccine (either mRNA-1273 (Moderna) or BNT162b2 (Pfizer) or any combination of both)

Procedures:

Based on their immunosuppressive treatment, patients can participate in one of the following strata:

* stratum A: patients receiving triple immunosuppressive therapy, consisting of a calcineurin inhibitor, MMF/MPA, and steroids In stratum A, patients will be randomized to one of two equally sized groups. Patients will receive a third or fourth vaccination of the mRNA-1273 vaccine (100 μg, i.m), with either continuation of MMF/MPA (A1) or discontinuation of MMF/MPA during one week before and one week after the third or fourth dose, respectively (A2).
* stratum B: patients receiving any combination of immunosuppressive drugs. In stratum B, patients will be randomized to one of three equally sized groups. Patients will receive another dose (100 μg, i.m) of the mRNA-1273 vaccine (B1), or two single doses of mRNA-1273 into the left and the right upper arm (2 x 100 μg, i.m; B2), or the Ad26.COV2.S vaccine (Janssen, 5x1010 viral particles, i.m; B3).

Main study parameters/endpoints:

The primary endpoint is the proportion of patients with an anti-S1 antibody concentration higher than 10 BAU/mL established at 28 days after the third or fourth vaccine administration. Within each stratum different vaccination strategies will be compared.

Secondary endpoints include:

* concentration of anti-S1 antibodies in serum at 28 days after the 3rd or 4th vaccine administration
* concentration of virus-neutralizing antibodies in serum
* SARS-CoV-2 specific T cell responses
* safety in terms of incidence of acute rejection and solicited local and systemic adverse events (AEs) after vaccination.
* antibody (IgG and IgA) responses in nasal mucosal fluid

Conditions

• Covid19
• Kidney Diseases
• Vaccine Response Impaired
• SARS-CoV2 Infection

Interventions

BIOLOGICAL

mRNA-1273

SARS-CoV-2 vaccination

BIOLOGICAL

Ad26.COV2.S vaccine

SARS-CoV-2 vaccination

Sponsors & Collaborators

• Radboud University Medical Center

  collaborator OTHER

• Erasmus Medical Center

  collaborator OTHER

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

  collaborator OTHER

• ZonMw: The Netherlands Organisation for Health Research and Development

  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

2021-10-21

Primary Completion

2022-03-12

Completion

2022-03-12

Countries

• Netherlands

Study Locations