Efficacy, Safety, and Immunogenicity of Vaccine Reimmunization With a Third Homologous Versus Heterologous Dose Against COVID-19 in Patients Undergoing Solid Organ Transplantation.

Study Overview
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Brief Summary
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Patients undergoing solid organ transplantation randomly selected from those who have received two doses of Spikevax (Moderna) vaccine, provided that a minimum of 8 weeks have elapsed from the second dose to the time of the start of the trial. It is planned to include 386 patients.

Detailed Description
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The main objective of this trial is to evaluate the immunogenicity of reimmunization against SARS-CoV-2 in patients undergoing solid organ transplantation with heterologous revaccination, testing whether in patients who received two doses of Spikevax Moderna vaccine there is a significant increase at 28 days in their antibody titers against SARS-CoV-2 after receiving a dose of Janssen. The secondary objectives of this trial are: To evaluate the efficacy of reimmunization against SARS-CoV-2 in subjects undergoing solid organ transplantation, in terms of incidence of infection and severity of COVID-19 after revaccination in the transplanted patient. To gain insight into the humoral and cellular immune response conferred by the sequential combination of both homologous and heterologous vaccination over one year, as well as its duration in subjects undergoing solid organ transplantation. To evaluate the safety of vaccines against SARS-CoV-2 in subjects undergoing solid organ transplantation. To determine the potential existence of differences in humoral (Anti S Ac) and cellular immune response depending on the immunosuppression regimen. To evaluate the occurrence of side effects, including rejection and anti-HLA and DSA antibodies after revaccination.

Official Title
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Randomized, Open-label, Adaptive, Controlled, Phase III Clinical Trial to Evaluate the Efficacy, Safety and Immunogenicity of Reimmunization With Third Dose of Homologous vs. Heterologous Vaccine Against COVID-19 in Patients Undergoing Solid Organ Transplantation: Liver, Heart, Kidney and Lung.

Conditions
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Covid19

Intervention / Treatment
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* Biological: Janssen vaccine
* Biological: Spikevax (Moderna) vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who underwent solid organ transplantation prior to revaccination against COVID-19. Patients who have received the full COVID-19 vaccination regimen with Spikevax (Moderna) vaccine, with a minimum of 8 weeks having elapsed from the second dose to the time of trial initiation. Age > 18 years. All participants must have previously agreed to participate in the study by signing the informed consent form. Exclusion Criteria: Having suffered SARS-CoV-2 infection at any time prior to inclusion in the study. Subjects without solid organ transplantation or with a different solid organ (e.g. pancreas transplantation) and without any type of immunosuppression (immunocompetent non-transplanted) from the general population. Age < 18 years Temperature of at least 38°C in the 24 hours prior to immunization or other clinically relevant acute symptomatology. Clinical manifestations compatible with COVID-19 infection at the time of evaccination. Known allergy or history of anaphylaxis or other serious adverse events to the administration of vaccines or their excipients. Any other condition that contraindicates vaccination against SARSCov2, including pregnancy. Having presented graft rejection in the 15 days prior to the start of the study. Any condition or situation that may interfere with the ability to maintain adherence to study procedures and visits.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HETEROLOGOUS VACCINE<br>COVID-19 Vaccine Janssen, injectable suspension | Biological: Janssen vaccine<br>* 0.5 ml millilitre(s) Intramuscular use<br>* Other names: EU/1/20/1525/001 EU/1/20/1525/002;|
| Active Comparator: HOMOLOGOUS VACCINE<br>Spikevax (Moderna), injectable dispersion | Biological: Spikevax (Moderna) vaccine<br>* 0.5 ml millilitre(s) Intramuscular use<br>* Other names: EU/1/20/1507/001;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in the production of anti-S1-RBD IgG antibodies. | Positivity for comparison before and after revaccination and according to homologous or heterologous vaccination will be quantified in the laboratory method units. | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the presence of activated T cells specific for SARS-CoV-2 (Sprotein). | T-cell response to SARS-CoV-2 will be analyzed by flow cytometry. | 1 year | 
| Changes in the phenotype of effector/memory/virgin B and T cell populations and subtypes of Th and NK cell populations. | T-cell response to SARS-CoV-2 will be analyzed by flow cytometry. | 1 year | 
| Incidence of symptomatic/asymptomatic COVID infection after revaccination. | Confirmed COVID-19 is defined as the presence of at least one of the following symptoms: fever, new onset or increased cough, new onset or increased shortness of breath, chills, new onset or increased muscle pain, loss of taste or smell, sore throat, diarrhea or vomiting, combined with a respiratory specimen, obtained during the symptomatic period, positive for SARS-CoV-2 by nucleic acid amplification (PCR)-based testing or antigen testing. | 1 year | 
| Number of patients with hospital admissions and/or visits to the emergency department for severe symptoms related to COVID-19 infection. | Confirmed COVID-19 is defined as the presence of at least one of the following symptoms: fever, new onset or increased cough, new onset or increased shortness of breath, chills, new onset or increased muscle pain, loss of taste or smell, sore throat, diarrhea or vomiting, combined with a respiratory specimen, obtained during the symptomatic period, positive for SARS-CoV-2 by nucleic acid amplification (PCR)-based testing or antigen testing. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vaccine, Covid-19, Liver Trasplant, Lung Trasplant, Heart Trasplant, Kidney Trasplant