NCT05030974

RECOVAC Repeated Vaccination Study

Completed Phase 4 Last updated 29 March 2022

What this trial tests

Phase 4 trial testing mRNA-1273 in Covid19 in 336 participants. Completed in 12 March 2022.

Timeline

21 October 2021

Primary endpoint
12 March 2022

12 March 2022

Quick facts

Lead sponsor	University Medical Center Groningen
Phase	Phase 4
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	prevention
Enrollment	336
Start date	21 October 2021
Primary completion	12 March 2022
Estimated completion	12 March 2022
Sites	4 locations across Netherlands

Drugs / interventions tested

• mRNA-1273 — full drug profile →
• Ad26.COV2.S vaccine — full drug profile →

Conditions studied

• Covid19 — all drugs for Covid19 →
• Kidney Diseases — all drugs for Kidney Diseases →
• Vaccine Response Impaired — all drugs for Vaccine Response Impaired →
• SARS-CoV2 Infection — all drugs for SARS-CoV2 Infection →

Sponsor

University Medical Center Groningen

Who can join

18 and older, any sex, with Covid19 or Kidney Diseases. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. RNA-based therapeutics: an overview and prospectus.
   Zhu Y, Zhu L, Wang X, Jin H. · · 2022 · cited 417× · PMID 35871216 · DOI 10.1038/s41419-022-05075-2
2. Advances in COVID-19 mRNA vaccine development.
   Fang E, Liu X, Li M, Zhang Z, et al · · 2022 · cited 368× · PMID 35322018 · DOI 10.1038/s41392-022-00950-y
3. COVID-19 vaccine development: milestones, lessons and prospects.
   Li M, Wang H, Tian L, Pang Z, et al · · 2022 · cited 298× · PMID 35504917 · DOI 10.1038/s41392-022-00996-y
4. Efficacy and safety of COVID-19 vaccines.
   Graña C, Ghosn L, Evrenoglou T, Jarde A, et al · · 2022 · cited 227× · PMID 36473651 · DOI 10.1002/14651858.cd015477
5. Immunogenicity and Risk Factors Associated With Poor Humoral Immune Response of SARS-CoV-2 Vaccines in Recipients of Solid Organ Transplant: A Systematic Review and Meta-Analysis.
   Manothummetha K, Chuleerarux N, Sanguankeo A, Kates OS, et al · · 2022 · cited 91× · PMID 35412626 · DOI 10.1001/jamanetworkopen.2022.6822
6. 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.
   Kho MML, Messchendorp AL, Frölke SC, Imhof C, et al · · 2023 · cited 62× · PMID 36354032 · DOI 10.1016/s1473-3099(22)00650-8
7. Vaccines for COVID-19: A Systematic Review of Immunogenicity, Current Development, and Future Prospects.
   Zhang Z, Shen Q, Chang H. · · 2022 · cited 44× · PMID 35572592 · DOI 10.3389/fimmu.2022.843928
8. Factors Associated With COVID-19 Vaccine Response in Transplant Recipients: A Systematic Review and Meta-analysis.
   Li J, Ayada I, Wang Y, den Hoed CM, et al · · 2022 · cited 30× · PMID 35761439 · DOI 10.1097/tp.0000000000004256