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Clinical Trial 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 booster strategy is therefore required to improve the efficacy of vaccination. Objective: To investigate the immunogenicity of booster SARS-CoV-2 vaccination strategies in kidney transplant patients. Study design: Prospective, multicentre, open-label randomized clinical trial Study population: Kidney transplant patients who did not sero-convert after two doses (100 μg, i.m.) of the mRNA-1273 SARS-CoV-2 vaccine (Moderna). Procedures: - stratum A: patients receiving triple immunosuppressive therapy, consisting of a calcineurin inhibitor, MMF/MPA, and steroids - A1: Third dose (100 μg, i.m) of the mRNA-1273 vaccine - A2: Third dose (100 μg, i.m) of the mRNA-1273 vaccine with discontinuation discontinuation of MMF/MPA - stratum B: patients receiving any combination of immunosuppressive drugs. - B1: third dose (100 μg, i.m) of the mRNA-1273 vaccine - B2: two single doses of mRNA-1273 into the left and the right upper arm (2 x 100 μg, i.m; B2) - B3: Ad26.COV2.S vaccine (Janssen, 5x1010 viral particles, i.m; B3).


Clinical Trial Description

2. OBJECTIVES Primary objective: To assess the immunogenicity (expressed as percentage of responders) of various COVID-19 booster vaccination strategies in kidney transplant patients that failed to mount a sufficient antibody response after two primary doses of the mRNA-1273 vaccine. Secondary Objectives: - To measure the concentration of SARS-CoV-2 spike S1-specific IgG antibodies in serum at 28 days after the 3rd vaccine administration - To assess the durability of the SARS-CoV-2 spike S1-specific IgG antibody response at 6 and 12 months after the 3rd vaccine administration - To measure the presence and titer of neutralizing anti-SARS-CoV-2 antibodies after booster vaccination - To evaluate SARS-CoV-2 specific T cell responses - To measure anti-S1 antibody (IgG and IgA) responses and neutralizing capacity of these antibodies in nasal mucosal fluid - To evaluate vaccine safety in terms of incidence of solicited local and systemic adverse events (AEs) graded according to severity, including the incidence of acute rejections within 6 months after the third vaccination . Exploratory Objectives: - To assess the association between baseline clinical and immunological parameters and the immune response to booster vaccinations - To correlate RNA-seq data at one week after vaccination to the subsequent antibody and T cell response - To assess the incidence of SARS-CoV-2 infection and outcome of COVID-19 disease during 12 months after the 3rd vaccine administration by questionnaire and by measurement of SARS-CoV-2 nucleocapsid-specific antibodies 3. STUDY DESIGN This is a prospective, multicentre, open-label, randomized study to evaluate the immunogenicity and safety of various booster vaccination strategies in kidney transplant patients without a sufficient antibody response after two doses of the mRNA-1273 vaccine. The four participating study sites are: Amsterdam UMC, ErasmusMC, Radboudumc and UMCG. Based on their immunosuppressive treatment, patients will participate in one of the following strata: - stratum A: patients treated with triple immunosuppressive therapy consisting of a calcineurin inhibitor, MMF/MPA, and steroids, - stratum B: patients treated with any combination of immunosuppressive drugs. In stratum A, patients will be randomized to one of two booster strategies:: - A1: 3rd dose of mRNA-1273 (100 μg, i.m) - A2: 3rd dose of mRNA-1273 (100 μg, i.m), with temporary discontinuation of MMF/MPA during one week before and one week after the 3rd dose In stratum B, patients will be randomized to one of three booster strategies: - B1: 3rd dose of mRNA-1273 (100 μg, i.m) - B2: 3rd dose of mRNA-1273 (100 μg, i.m) in both upper arms - B3: Ad26.COV2.S vaccine (Janssen, 5x1010 viral particles i.m.) To assess the immune response after vaccination, blood samples will be collected at baseline (i.e. prior to third dose administration), at 28 days, and at 6 and 12 months after the third dose administration. A complete blood count, kidney function, and liver enzymes will be determined at the same time points. In a subset of patients we will collect a blood sample at 1 week after the booster administration for specific immunological assays. For safety reasons, a blood sample will be collected in stratum A at one and two weeks after discontinuing MMF/MPA. The maximum volume of blood collected for this study is 62.5 mL per timepoint, and no more than 200 mL for the one year study period, which is well within the safe limits of blood collection for clinical studies. Nasal mucosal lining fluid (MLF) will be collected for assessment of secreted mucosal antibodies at the same time points used to collect blood. MLF will be collected by use of soft synthetic absorptive matrix (SAM) strips, which are gently inserted into one nostril of the participant and placed along the surface of the inferior turbinate. The index finger is then lightly pressed against the side of the nostril to keep the SAM strip in place and to allow MLF absorption for 60 seconds (see Figure), after which the SAM strip is placed back in the protective plastic tube. The procedure may tickle slightly but is completely painless. The occurrence of acute rejection and COVID-19 will be monitored during 6 and 12 months after the third vaccine administration, respectively. To evaluate vaccination related AEs, patients will be asked to collect solicited local and systemic AEs for 7 days after each vaccination using a questionnaire, as vaccination related AEs are mainly expected in the first week after vaccination. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT05030974
Study type Interventional
Source University Medical Center Groningen
Contact Jan-Stephan F Sanders, MD PhD
Phone +31503616161
Email [email protected]
Status Not yet recruiting
Phase Phase 4
Start date October 2021
Completion date January 2023

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