To assess the efficacy (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.
ID
Source
Brief title
Condition
- Other condition
- Renal disorders (excl nephropathies)
Synonym
Health condition
niertransplantatie
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
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.
Secondary outcome
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
Background summary
COVID-19 is associated with severely increased morbidity and mortality in
kidney transplant patients. Therefore, effective SARS-CoV-2 vaccination is of
great clinical importance in these patients. Available data show that the
humoral and cellular 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). A booster strategy is
therefore required to improve the efficacy of vaccination.
Study objective
To assess the efficacy (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.
Study design
Prospective open label randomized multicentre study.
Intervention
In stratum A, patients will be randomized to one of two booster strategies:
* A1: 3rd dose of mRNA-1273 (100 *g, i.m)
* A2: 3rd dose of mRNA-1273 (100 *g, 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 *g, i.m)
* B2: 3rd dose of mRNA-1273 (100 *g, i.m) in both upper arms
* B3: Ad26.COV2.S vaccine (Janssen, 5x1010 viral particles i.m.)
Study burden and risks
In general:
Risks are associated with 4 or 6 venapunctions with a maximum of 62,5 ml
withdrawal of blood per session.
Specific:
In group A2 subjects will interrupt the use of MMF/MPA during two weeks. This
temporary interruption of the use of one of the immunosuppressive drugs may
theoretically increase the risk of graft rejection. These subjects will have
two more bloodsamples drawn (at one and two weeks after discontinuing
immunosuppressives) to monitor this risk.
In group B2 standard dose of 100*g mRNA-1273 will be given in both arms, what
makes a double dose.
Hanzeplein 1
Groningen 9700RB
NL
Hanzeplein 1
Groningen 9700RB
NL
Listed location countries
Age
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 <
10 BAU/mL measured between 25 and 56 days after the second dose of the
mRNA-1273 vaccine with a validated test
4. Capable of understanding the purpose and risks of the study, fully informed
and given written informed consent (signed informed consent form has been
obtained)
Additional inclusion criteria to be eligible for stratum A:
5. Maintenance immunosuppressive therapy consisting of a calcineurin inhibitor
(tacrolimus or cyclosporine), MMF/MPA, and prednisone
6. In case of tacrolimus treatment: last tacrolimus pre-dose level while on
current dosage above 4 *g/l
7. In case of cyclosporine treatment: last cyclosporine pre-dose level while on
current dosage above 75 *g/l
8. Prednisone dose at least 5 mg/day
9. First or second transplantation
10. Calculated level of panel reactive antibodies prior to last transplantation
below 85%
11. No signs of acute rejection during the preceding year
Exclusion criteria
1. Multi-organ transplant recipient
2. Previous or active COVID-19 disease
3. Active malignancy, except non-melanoma skin cancer
4. Inherited immune deficiency
5. Infection with Human Immunodeficiency Virus (HIV)
6. Administration of T cell, B cell, or plasma cell depleting antibodies during
the last 6 months
7. Any vaccination within a month before enrolment
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2021-004558-44-NL |
| CCMO | NL78963.042.21 |