COVID-19 is associated with severely increased morbidity and mortality in kidney transplant patients. Available data show that the immune response after a standard regimen of 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). MedDRA version: 23.1 Level: LLT Classification code 10084401 Term: COVID-19 respiratory infection System Organ Clas
Conditions
Interventions
Trade Name: Spikevax
Pharmaceutical Form: Solution for injection
INN or Proposed INN: INN-COVID-19 mRNA Vaccine
Other descriptive name: COVID-19 mRNA vaccine Moderna (CX-024414)
Concentration unit: mg
Sponsors
UMCG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age 18 years or older 2. Received 2 doses of mRNA-1273 according to the recommended vaccination schedule, with the last administration within the last nine months 3. Insufficient response to vaccination, defined as anti-spike IgG in serum =65 years) yes F.1.3.1 Number of subjects for this age range 60
Exclusion criteria
Exclusion criteria: 1. Multi-organ transplant recipient 2. 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). 3. Previous or active COVID-19 disease 4. Active malignancy, except non-melanoma skin cancer 5. Inherited immune deficiency 6. Infection with Human Immunodeficiency Virus (HIV) 7. Administration of T cell, B cell, or plasma cell depleting antibodies during the last 6 months 8. Any vaccination within a month before enrolment 9. Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main 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 Objective: - 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 .;Primary end point(s): The primary endpoint is the percentage of subjects with a serum anti-S1 IgG concentration =10 BAU/mL at 28 days after the third vaccine administration.;Timepoint(s) of evaluation of this end point: 28 days after the third (and possibly a fourth) vaccination | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: 6 and 12 months after the third vaccination;Secondary end point(s): o SARS-CoV-2 specific antibody concentrations in serum at 28 days after the 3rd vaccine administration o SARS-CoV-2 specific antibody concentrations in serum at 6 and 12 months after the 3rd vaccine administration o The titer of neutralizing anti-SARS-CoV-2 antibodies at 28 days after the 3rd vaccine administration o SARS-CoV-2 specific antibody concentrations in nasal mucosal fluid at 28 days and 6 months after the 3rd vaccine administration o SARS-CoV-2 specific T cell responses at 28 days after the third vaccine administration by: ? Measuring interferon-gamma concentration in whole blood after ex vivo stimulation with SARS-CoV-2 specific peptides ? Measuring ex vivo production of T cell related cytokines by peripheral blood mononuclear cells (PBMC) in ELISpot assays o Incidence of acute rejection within 6 months after the third vaccine administration o Safety in terms of incidence of solicited local and systemic adverse events (AEs) within one week after vaccine administration graded according to severity. The following items will be specifically addressed: ? Percentage of participants reporting local reactions (pain at the injection site, redness and swelling) within 7 days after vaccine administration ? Percentage of participants reporting systemic events (fever, fatigue, headache, chills, vomiting, diarrhea, new of worsened muscle pain, and new or worsened joint pain) within 7 days after vaccine administration ? Percentage of participants with serious adverse events within 6 months after the third vaccine administration | — |
Countries
Netherlands
Contacts
Public ContactJSF Sanders
UMCG
Outcome results
None listed