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

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.

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.

Study Overview

• Status: Withdrawn
• Conditions: Covid19
• Intervention / Treatment: Biological: Janssen vaccine; Biological: Spikevax (Moderna) vaccine

Detailed Description

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:

1. 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.
2. 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.
3. To evaluate the safety of vaccines against SARS-CoV-2 in subjects undergoing solid organ transplantation.
4. To determine the potential existence of differences in humoral (Anti S Ac) and cellular immune response depending on the immunosuppression regimen.
5. To evaluate the occurrence of side effects, including rejection and anti-HLA and DSA antibodies after revaccination.

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: María del Mar García Saiz; Phone Number: 942 20 33 33; Email: mmar.garcia@scsalud.es
• Study Contact Backup: Name: Lucía Lavín Alconero; Phone Number: 942 20 33 89; Email: eclinicos5@idival.org

Study Locations

• Spain
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Hospital Universitario Marques de Valdecilla

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients who underwent solid organ transplantation prior to revaccination against COVID-19.
2. 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.
3. Age > 18 years.
4. All participants must have previously agreed to participate in the study by signing the informed consent form.

Exclusion Criteria:

1. Having suffered SARS-CoV-2 infection at any time prior to inclusion in the study.
2. 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.
3. Age < 18 years
4. Temperature of at least 38°C in the 24 hours prior to immunization or other clinically relevant acute symptomatology.
5. Clinical manifestations compatible with COVID-19 infection at the time of evaccination.
6. Known allergy or history of anaphylaxis or other serious adverse events to the administration of vaccines or their excipients.
7. Any other condition that contraindicates vaccination against SARSCov2, including pregnancy.
8. Having presented graft rejection in the 15 days prior to the start of the study.
9. Any condition or situation that may interfere with the ability to maintain adherence to study procedures and visits.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HETEROLOGOUS VACCINE; COVID-19 Vaccine Janssen, injectable suspension	Biological: Janssen vaccine; 0.5 ml millilitre(s) Intramuscular use; Other Names: Janssen Biologics B.V.; EU/1/20/1525/001 EU/1/20/1525/002
Active Comparator: HOMOLOGOUS VACCINE; Spikevax (Moderna), injectable dispersion	Biological: Spikevax (Moderna) vaccine; 0.5 ml millilitre(s) Intramuscular use; Other Names: MODERNA BIOTECH SPAIN, S.L.; EU/1/20/1507/001

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Instituto de Investigación Marqués de Valdecilla

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2021
• Primary Completion (Anticipated): September 1, 2021
• Study Completion (Anticipated): September 1, 2021

Study Registration Dates

• First Submitted: September 8, 2021
• First Submitted That Met QC Criteria: September 16, 2021
• First Posted (Actual): September 17, 2021

Study Record Updates

• Last Update Posted (Actual): March 2, 2023
• Last Update Submitted That Met QC Criteria: February 28, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Vaccine; Covid-19; Liver Trasplant; Lung Trasplant; Heart Trasplant; Kidney Trasplant
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: REIN-TX

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No