Covid19Phase 4NCT05030974
RECOVAC Repeated Vaccination Study
A Phase 4 study testing mRNA-1273 and Ad26.COV2.S vaccine in people with Covid19 and Kidney Diseases, run by University Medical Center Groningen at 4 sites in Netherlands.
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Covid19, Kidney Diseases, Vaccine Response Impaired
- What is being tested?
- mRNA-1273 and Ad26.COV2.S vaccine
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 336 participants
- Where
- 4 sitesNetherlands
- Study dates
- 21 Oct 2021to 12 Mar 2022
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 years or older
- Received 2 doses of mRNA-1273 (stratum B) according to the recommended vaccination schedule, with the last administration within the last nine months. For stratum A, also patients who received 2 doses of BNT162b2 and/or a third dose with a mRNA vaccine (mRNA-1273 or BNT162b2) within the last three months are eligible.
- At least 6 months after kidney transplantation
- Negative seroresponse 14 to 56 days after vaccination, measured by a validated anti-spike IgG assay of which the definition is dependent on the assay that is used.
- Eligible for COVID-19 vaccination as described by the instructions of the manufacturers of the vaccine (Moderna and Janssen)
- Capable of understanding the purpose and risks of the study, fully informed and given written informed consent (signed informed consent form has been obtained)
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- Willing to adhere to the protocol and be available during the study period
- Additional inclusion criteria to be eligible for stratum A:
- Maintenance immunosuppressive therapy consisting of a calcineurin inhibitor (tacrolimus or cyclosporine), MMF/MPA, and prednisone
- In case of tacrolimus treatment: last tacrolimus pre-dose level while on current dosage above 4 μg/l
- In case of cyclosporine treatment: last cyclosporine pre-dose level while on current dosage above 75 μg/l
- Prednisone dose at least 5 mg/day
- First or second transplantation
- Calculated level of panel reactive antibodies prior to last transplantation below 85%
- No signs of acute rejection during the preceding year
Who cannot join
- Multi-organ transplant recipient
- 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).
- Previous or active COVID-19 disease
- Active malignancy, except non-melanoma skin cancer
- Inherited immune deficiency
- Infection with Human Immunodeficiency Virus (HIV)
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- Administration of T cell, B cell, or plasma cell depleting antibodies during the last 6 months
- Any vaccination within a week before enrolment
- Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection.
- Additional exclusion criteria for stratum B:
- History of recurrent venous thrombosis or venous thrombosis <2 years before baseline
- Immune-mediated diseases associated with thrombocytopenia such as ITP and aHUS
Trial locations and contacts
4 sites in 1 country.
Netherlands4 sites
Amsterdam UMC
Amsterdam, North Holland
University Medical Center Groningen
Groningen
Radboud umc
Nijmegen, Gelderland
Erasmus mc
Rotterdam, South Holland
About this study
Official title: Optimal Repeated Dose Strategy for SARS-CoV-2 Vaccination in Kidney Transplant Patients A Prospective, Randomized Multicenter Study by the REnal Patients COVID-19 VACcination (RECOVAC) Consortium
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.
Read more
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
Read the detailed description
- OBJECTIVES
Primary objective:
To assess the immunogenicity (expressed as percentage of responders) of various COVID-19 third or fourth vaccination strategies in kidney transplant patients that failed to mount a sufficient antibody response after two or three primary doses of a mRNA vaccine (either mRNA-1273 (Moderna) or BNT162b2 (Pfizer) or any combination of both).
Secondary Objectives:
- To measure the concentration of SARS-CoV-2 spike S1-specific IgG antibodies in serum at 28 days after the 3rd or 4th vaccine administration
- To measure the presence and titer of neutralizing anti-SARS-CoV-2 antibodies after third or fourth 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.
Exploratory Objectives:
- To assess the association between baseline clinical and immunological parameters and the immune response to third or fourth vaccinations
- To correlate RNA-seq data at one week after vaccination to the subsequent antibody and T cell response
- STUDY DESIGN
This is a prospective, multicentre, open-label, randomized study to evaluate the immunogenicity and safety of various third or fourth vaccination strategies in kidney transplant patients without a sufficient antibody response after two or three primary doses of a mRNA vaccine (either mRNA-1273 (Moderna) or BNT162b2 (Pfizer) or any combination of both).
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 third or fourth vaccination strategies:
- A1: one extra dose of mRNA-1273 (100 μg, i.m)
- A2: one extra 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 third vaccination 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) and at 28 days after the third or fourth 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 third vaccin 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 66 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, after which the SAM strip is placed back in the protective plastic tube. The procedure may tickle slightly but is completely painless.
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.
- Being tested
- mRNA-1273, Ad26.COV2.S vaccine
- Medical subject headings
- COVID-19, Kidney Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
mRNA-1273Biological
SARS-CoV-2 vaccination
Ad26.COV2.S vaccineBiological
SARS-CoV-2 vaccination
| Study group | Role | What they receive |
|---|---|---|
| stratum A1 - one extra dose of mRNA-1273 | Active comparator | Patients treated with triple immunosuppressive therapy consisting of a calcineurin inhibitor, MMF/MPA, and steroids, receiving a 3rd or 4th dose of mRNA-1273 (100 μg, i.m) Receives: Biological: mRNA-1273 |
| stratum A2 - one extra dose of mRNA-1273 with discontinuation of MMF/MPA | Active comparator | patients treated with triple immunosuppressive therapy consisting of a calcineurin inhibitor, MMF/MPA, and steroids, receiving a 3rd or 4th dose of mRNA-1273 (100 μg, i.m), with temporary discontinuation of MMF/MPA during one week before and one week after the extra dose Receives: Biological: mRNA-1273 |
| stratum B1 - 3rd dose of mRNA-1273 | Active comparator | patients treated with any combination of immunosuppressive drugs, receiving a 3rd dose of mRNA-1273 (100 μg, i.m) Receives: Biological: mRNA-1273 |
| statum B2 - 3rd double dose of mRNA-1273 | Active comparator | patients treated with any combination of immunosuppressive drugs, receiving a 3rd dose of mRNA-1273 (100 μg, i.m) in both upper arms Receives: Biological: mRNA-1273 |
| stratum B3 - Ad26.COV2.S vaccine | Active comparator | patients treated with any combination of immunosuppressive drugs, receiving a 3rd COVID vaccination with Ad26.COV2.S vaccine (Janssen, 5x1010 viral particles i.m.) Receives: Biological: Ad26.COV2.S vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Positive SARS-CoV-2 seroresponse
The percentage of subjects with a serum anti-S1 IgG concentration ≥10 BAU/mL after the third or fourth vaccine administration
Measured: 28 days after third vaccination
Secondary outcomes (6)
SARS-CoV-2 antibody concentration
SARS-CoV-2 anti-S1 IgG concentration in serum after third or fourth vaccine administration
Measured: 28 days after vaccination
Virus-neutralizing capacity of SARS-CoV-2 antibodies
The titer of neutralizing anti-SARS-CoV-2 antibodies after third or fourth vaccine administration
Measured: 28 days after vaccination
Mucosal SARS-CoV-2 antibodies
Concentrations of SARS-CoV-2 specific antibodies (IgG and IgA) in nasal fluid after third or fourth vaccine administration
Measured: 28 days after vaccination
SARS-CoV-2 specific T cell response
- Interferon-gamma concentration in whole blood after ex vivo stimulation with SARS-CoV-2 specific peptides
- Ex vivo production of T cell related cytokines by peripheral blood mononuclear cells (PBMC) in ELISpot assays after third vaccine administration
Measured: 28 days after vaccination
Solicited local and systemic adverse events
Percentage of participants reporting local reactions (pain at the injection site, redness and swelling) and systemic events (fever, fatigue, headache, chills, vomiting, diarrhea, new of worsened muscle pain, and new or worsened joint pain) after third or fourth vaccine administration
Measured: within 7 days after vaccination
Serious adverse events
Percentage of participants with serious adverse events after third or fourth vaccine administration
Measured: within 28 days after vaccination
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Sep 2021
- Study start21 Oct 2021
- Primary completion12 Mar 2022
- Study completion12 Mar 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Covid19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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 third or fourth vaccination strategies: * A1: one extra dose of mRNA-1273 (100 μg, i.m) * A2: one extra 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 third vaccination 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.)
- Masking
- None (open label)
- Enrolment
- 336 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Medical Center Groningen
- Sponsor type
- University, hospital or other
- Collaborators
- Radboud University Medical Center, Erasmus Medical Center, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), ZonMw: The Netherlands Organisation for Health Research and Development
- Responsible party
- Principal investigator, J.S.F. Sanders, University Medical Center Groningen
- Investigators
- Jan-Stephan F Sanders, MD PhD, Principal investigator, University Medical Center Groningen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05030974
- Sponsor's protocol ID
- NL78963.042.21
- Status last verified
- Mar 2022
- First submitted
- 20 Aug 2021
- Last updated
- 29 Mar 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: The data of this study will be available from the principal investigator, upon reasonable request.
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.
PubMed 39272117Malahe 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.
PubMed 38902860Kho 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.
PubMed 36354032
Study at a glance
From the registry record, last updated by the sponsor on 29 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Optimal Repeated Dose Strategy for SARS-CoV-2 Vaccination in Kidney Transplant Patients A Prospective, Randomized Multicenter Study by the REnal Patients COVID-19 VACcination (RECOVAC) Consortium
- ClinicalTrials.gov ID
- NCT05030974
- Acronym / sponsor ID
- NL78963.042.21
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 336 participants (actual)
- Lead sponsor
- University Medical Center GroningenUniversity, hospital or other
- Collaborators
- Radboud University Medical Center, Erasmus Medical Center, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), ZonMw: The Netherlands Organisation for Health Research and Development
- Study start
- 21 Oct 2021 (actual)
- Primary completion
- 12 Mar 2022 (actual)
- Study completion
- 12 Mar 2022 (actual)
- First posted
- 1 Sep 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed description
- OBJECTIVES
Primary objective:
To assess the immunogenicity (expressed as percentage of responders) of various COVID-19 third or fourth vaccination strategies in kidney transplant patients that failed to mount a sufficient antibody response after two or three primary doses of a mRNA vaccine (either mRNA-1273 (Moderna) or BNT162b2 (Pfizer) or any combination of both).
Secondary Objectives:
- To measure the concentration of SARS-CoV-2 spike S1-specific IgG antibodies in serum at 28 days after the 3rd or 4th vaccine administration
- To measure the presence and titer of neutralizing anti-SARS-CoV-2 antibodies after third or fourth 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.
Exploratory Objectives:
- To assess the association between baseline clinical and immunological parameters and the immune response to third or fourth vaccinations
- To correlate RNA-seq data at one week after vaccination to the subsequent antibody and T cell response
- STUDY DESIGN
This is a prospective, multicentre, open-label, randomized study to evaluate the immunogenicity and safety of various third or fourth vaccination strategies in kidney transplant patients without a sufficient antibody response after two or three primary doses of a mRNA vaccine (either mRNA-1273 (Moderna) or BNT162b2 (Pfizer) or any combination of both).
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 third or fourth vaccination strategies:
- A1: one extra dose of mRNA-1273 (100 μg, i.m)
- A2: one extra 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 third vaccination 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) and at 28 days after the third or fourth 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 third vaccin 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 66 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, after which the SAM strip is placed back in the protective plastic tube. The procedure may tickle slightly but is completely painless.
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
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
- Model description
- 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 third or fourth vaccination strategies: * A1: one extra dose of mRNA-1273 (100 μg, i.m) * A2: one extra 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 third vaccination 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.)
| Arm | Type | Receives |
|---|---|---|
| stratum A1 - one extra dose of mRNA-1273 | Active comparator | Biological: mRNA-1273Patients treated with triple immunosuppressive therapy consisting of a calcineurin inhibitor, MMF/MPA, and steroids, receiving a 3rd or 4th dose of mRNA-1273 (100 μg, i.m) |
| stratum A2 - one extra dose of mRNA-1273 with discontinuation of MMF/MPA | Active comparator | Biological: mRNA-1273patients treated with triple immunosuppressive therapy consisting of a calcineurin inhibitor, MMF/MPA, and steroids, receiving a 3rd or 4th dose of mRNA-1273 (100 μg, i.m), with temporary discontinuation of MMF/MPA during one week before and one week after the extra dose |
| stratum B1 - 3rd dose of mRNA-1273 | Active comparator | Biological: mRNA-1273patients treated with any combination of immunosuppressive drugs, receiving a 3rd dose of mRNA-1273 (100 μg, i.m) |
| statum B2 - 3rd double dose of mRNA-1273 | Active comparator | Biological: mRNA-1273patients treated with any combination of immunosuppressive drugs, receiving a 3rd dose of mRNA-1273 (100 μg, i.m) in both upper arms |
| stratum B3 - Ad26.COV2.S vaccine | Active comparator | Biological: Ad26.COV2.S vaccinepatients treated with any combination of immunosuppressive drugs, receiving a 3rd COVID vaccination with Ad26.COV2.S vaccine (Janssen, 5x1010 viral particles i.m.) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Age 18 years or older
- Received 2 doses of mRNA-1273 (stratum B) according to the recommended vaccination schedule, with the last administration within the last nine months. For stratum A, also patients who received 2 doses of BNT162b2 and/or a third dose with a mRNA vaccine (mRNA-1273 or BNT162b2) within the last three months are eligible.
- At least 6 months after kidney transplantation
- Negative seroresponse 14 to 56 days after vaccination, measured by a validated anti-spike IgG assay of which the definition is dependent on the assay that is used.
- Eligible for COVID-19 vaccination as described by the instructions of the manufacturers of the vaccine (Moderna and Janssen)
Key exclusion criteria (12 listed)
- Multi-organ transplant recipient
- 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).
- Previous or active COVID-19 disease
- Active malignancy, except non-melanoma skin cancer
- Inherited immune deficiency
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| mRNA-1273SARS-CoV-2 vaccination | Biological | statum B2 - 3rd double dose of mRNA-1273, stratum A1 - one extra dose of mRNA-1273, stratum A2 - one extra dose of mRNA-1273 with discontinuation of MMF/MPA, stratum B1 - 3rd dose of mRNA-1273 |
| Ad26.COV2.S vaccineSARS-CoV-2 vaccination | Biological | stratum B3 - Ad26.COV2.S vaccine |
Primary outcome
Positive SARS-CoV-2 seroresponse
Time frame: 28 days after third vaccination
The percentage of subjects with a serum anti-S1 IgG concentration ≥10 BAU/mL after the third or fourth vaccine administration
6 secondary outcomes
SARS-CoV-2 antibody concentration
Time frame: 28 days after vaccination
Virus-neutralizing capacity of SARS-CoV-2 antibodies
Time frame: 28 days after vaccination
Mucosal SARS-CoV-2 antibodies
Time frame: 28 days after vaccination
SARS-CoV-2 specific T cell response
Time frame: 28 days after vaccination
Solicited local and systemic adverse events
Time frame: within 7 days after vaccination
Serious adverse events
Time frame: within 28 days after vaccination
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Mar 2022.
- Derived from this study: PubMed 39272117Vervoort 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.
- Derived from this study: PubMed 38902860Malahe 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.
- Derived from this study: PubMed 36354032Kho 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.
- Individual participant dataSharing planned: No. The data of this study will be available from the principal investigator, upon reasonable request.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jan-Stephan F Sanders, MD PhD principal investigator
University Medical Center Groningen
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing mRNA-1273 and Ad26.COV2.S vaccine in people with Covid19 and Kidney Diseases, run by University Medical Center Groningen at 4 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Positive SARS-CoV-2 seroresponse (time frame: 28 days after third vaccination). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05030974, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Mar 2022.