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

Timeline

Start

2021-10-21

Primary completion

2022-03-12

Completion

2022-03-12

Publications

• Vervoort JPM, Konijn WS, Jansen DEMC, Boersma C, de Zeeuw J, Ho-Dac-Pannekeet MM, Gansevoort RT, Messchendorp AL, Sanders JSF, de Wildt-Liesveld R. Patient engagement as a collaborative process in a large Dutch COVID-19 vaccination study (RECOVAC) - insight into the contribution of patient engagement and learnings for the future. Res Involv Engagem. 2024 Sep 13;10(1):96. doi: 10.1186/s40900-024-00622-x.
• Malahe SRK, den Hartog Y, Rietdijk WJR, van Baarle D, de Kuiper R, Reijerkerk D, Ras AM, Geers D, Diavatopoulos DA, Messchendorp AL, van der Molen RG, Imhof C, Frolke SC, Bemelman FJ, Gansevoort RT, Hilbrands LB, Sanders JF, GeurtsvanKessel CH, Kho MML, de Vries RD, Reinders MEJ, Baan CC; On behalf of RECOVAC Consortium. Repeated COVID-19 Vaccination Drives Memory T- and B-cell Responses in Kidney Transplant Recipients: Results From a Multicenter Randomized Controlled Trial. Transplantation. 2024 Dec 1;108(12):2420-2433. doi: 10.1097/TP.0000000000005119. Epub 2024 Nov 21.
• Kho MML, Messchendorp AL, Frolke SC, Imhof C, Koomen VJ, Malahe SRK, Vart P, Geers D, de Vries RD, GeurtsvanKessel CH, Baan CC, van der Molen RG, Diavatopoulos DA, Remmerswaal EBM, van Baarle D, van Binnendijk R, den Hartog G, de Vries APJ, Gansevoort RT, Bemelman FJ, Reinders MEJ, Sanders JF, Hilbrands LB; RECOVAC collaborators. Alternative strategies to increase the immunogenicity of COVID-19 vaccines in kidney transplant recipients not responding to two or three doses of an mRNA vaccine (RECOVAC): a randomised clinical trial. Lancet Infect Dis. 2023 Mar;23(3):307-319. doi: 10.1016/S1473-3099(22)00650-8. Epub 2022 Oct 27.

Drugs

Indications