COVE Transplant Study

Site PIs: Abhijit (Ajit) Limaye, MD and Cynthia Fisher, MD MPH

Sponsor: Moderna Inc.

Study Design: Phase 3b, Open-Label, Safety and Immunogenicity Study

In 2021, the UW SOT-ID Research team partnered with Moderna, Inc., to study the immune response of liver and kidney transplant patients when administered the mRNA-1273 SARS-CoV2 vaccine to better understand how people who are immunosuppressed respond to these new vaccines.

Status: Enrollment for this study has ended. At the University of Washington, we enrolled over 50 participants in this study.

Background

Immunocompromised populations, such as individuals who are solid organ transplant (SOT) recipients, are at especially high risk for increased complications of COVID-19 because of their associated co-morbidities and chronic immunosuppression.

Recent data shows that this patient population’s response to mRNA-based vaccines is lower due to their immunocompromised status.

ModernaTX is studying the mRNA-1273 study vaccine for the prevention of COVID-19 in participants who have some types of solid organ transplant. Healthy participants are being included in the study to compare the results from these participants to those who have had a kidney or liver transplant.

The effectiveness of the mRNA-1273 study vaccine in people who have received a solid organ transplant is not known thus through this study, we can learn about the safety and side effects of the study vaccine and how the body responds to the study vaccine (the “immune response”). SOT patients’ immune response to the study vaccine will be measured through blood tests, and COVID-19 through Nasopharyngeal (NP) swabs.

Rationale

Moderna has developed a rapid-response, proprietary vaccine platform based on a messenger RNA (mRNA) delivery system. The platform is based on the principle and observations that cells in vivo can take up mRNA, translate it, and then display protein viral antigen(s) on the cell surface. The delivered mRNA does not enter the cellular nucleus or interact with the genome, is nonreplicating, and is expressed transiently. Moderna is using its mRNA-based platform to develop a novel lipid nanoparticle (LNP) encapsulated mRNA-based vaccine against SARS-CoV-2 (mRNA-1273).

(NEEDS CITATION)

This study is being conducted to learn about the safety and side effects of the study vaccine and how SOT recipients respond to the study vaccine.

There is also a medical need to explore the use of a booster dose of the mRNA COVID-19 study vaccine after completion of the primary series study vaccination against SARS-CoV-2 in recipients of solid organ transplants

Study Design

This is a Phase 3b, open-label study to evaluate the safety, reactogenicity, and immunogenicity of mRNA-1273 SARS-CoV-2 vaccine in SOT recipients and healthy controls. Adult kidney and liver transplant recipients and healthy control participants who are at least 18 years of age will be enrolled. Approximately 240 adult participants (220 previously vaccinated or unvaccinated participants who have had a kidney or liver transplant and 20 unvaccinated healthy adults) will be enrolled.

Participants will receive 2 doses of 100 µg of mRNA-1273 (vaccine) 28 days apart (window of -3/+7 days for the second dose). The SOT recipients will be offered the opportunity to receive a 3rd primary dose of vaccine at Day 85 (window of -3/+7 days for the third dose). Participants will also be offered a chance to receive a 100 µg BD of mRNA-1273 who are at least 4 months from the last dose. SOT recipients who completed primary COVID-19 vaccination series under EUA will receive a 100 µg BD on BD-D1.

Apart from vaccinations, participants have research visits where blood and nasal pharyngeal (NP swabs) are collected at specific time points. Follow up visits are also conducted through telephone contact. Participants that received 2 doses are followed up for one year after their last vaccination. Participants that received 3 or more doses are followed up for 6 months after their last vaccination.

Primary Outcomes

  • To evaluate the safety of 100 µg mRNA-1273 administered in 2-dose or 3-dose regimens

  • To evaluate the reactogenicity of 100 µg mRNA-1273 administered in 2-dose or 3- dose regimen

  • To evaluate serum neutralizing antibody (nAb) responses to doses of 100 µg mRNA-1273 obtained 28 days after the second dose or third dose

Secondary Outcomes

  • To evaluate the persistence of the immune response to 2 or 3 doses of 100 µg mRNA-1273, as assessed by the level of anti-SARS-CoV-2 Spike (S) specific binding antibody (bAb) through 1 year after dose 2 or dose 3

  • To evaluate the persistence of the immune response to 2 or 3 doses of 100 µg mRNA-1273, as assessed by the level of nAb through 1 year after dose 2 or dose 3

  • To describe the incidence of asymptomatic SARS-CoV-2 infection after mRNA-1273 vaccination in adult solid organ transplant (SOT) recipients and healthy adult participants with negative SARS-CoV-2 at baseline

  • To describe the incidence of coronavirus disease 2019 (COVID-19) after vaccination with mRNA-1273 in SOT recipients and healthy participants

  • To describe changes in liver and renal function through laboratory tests over time in SOT recipients after vaccination with mRNA-1273 vaccine

  • To describe changes in immunosuppressant medications in SOT recipients after vaccination with mRNA-1273 vaccine