HORUS-Cytomegalovirus Open Proof-of-concept Exploratory Trial

Phase 4Not Yet RecruitingNCT07570433

Oriol Manuel100 enrolled

Overview

Cytomegalovirus (CMV) remains a significant cause of morbidity and mortality following organ transplantation. Cell-mediated immunity plays a crucial role in controlling CMV replication after transplantation. Immune monitoring involves the use of immune biomarkers-primarily those assessing cell-mediated immunity-to dynamically estimate the risk of CMV replication. This approach allows for the individualization of preventive and therapeutic strategies, improving patient outcomes. The HORUS consortium is a comprehensive European research initiative aimed at providing an in-depth assessment of immune signatures associated with CMV immune control in SOT recipients. One of the ultimate goals of the HORUS project is to leverage these immune signatures to design and implement a clinical trial evaluating their feasibility and impact in routine clinical practice. As part of this initiative, we introduce the HORUS-COPE trial, designed to assess the effect of immune modulation on CMV replication kinetics and to explore the performance of a selected immune signature during antiviral therapy for CMV infection to stratify patients based on their risk of not responding to immune modulation. Specifically, immune modulation consists of either: 1. a 50% dose reduction of an antimetabolite agent- mycophenolate mofetil \[MMF, Cellcept®\] or enteric-coated mycophenolate sodium \[EC-MPS, Myfortic®\]; hereafter referred to as mycophenolic acid \[MPA\]) 2. a switch from MPA to a mammalian target of rapamycin inhibitor (mTORi) everolimus, together with an adapted dose of tacrolimus.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Interventions

50% reduction in the dose of MPADRUG

50% reduction in the dose of MPA with standard antiviral therapy

Switch from MPA to a mammalian target of rapamycin inhibitor (mTORi), together with an adapted dose of tacrolimusDRUG

Switch from MPA to a mammalian target of rapamycin inhibitor (mTORi), together with an adapted dose of tacrolimus, with standard antiviral therapy

standard antiviral therapy along with maintenance of their initial immunosuppressive therapy.DRUG

standard antiviral therapy along with maintenance of their initial immunosuppressive therapy (control group)

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Clinically stable adult patients (aged 18 years or older) who have received a solid organ transplant (e.g., kidney, liver, heart, lung, pancreas) and developed clinically significant CMV infection as determined by positive CMV PCR. * On maintenance therapy of tacrolimus, MPA, +/- steroids. * Informed consent signed. Exclusion Criteria: * Active acute graft rejection or significant graft dysfunction requiring modification of the current immunosuppressive regimen, in the opinion of the investigator. * Receipt of more than 72 hours of antiviral therapy for CMV infection prior to enrolment, before randomization, including valganciclovir and/or IV ganciclovir therapy * Known intolerance or hypersensitivity to mTOR inhibitors or to any component of the everolimus formulation. * Any medical condition that constitutes a contraindication to everolimus use, as judged by the investigator. * Additional exclusion criteria for French sites: * Patient not affiliated to the French social security system * Patient under legal protection (guardianship, curatorship).

Locations (4)

Centre hospitalier universitaire Bordeaux (CHU Bordeaux)

Bourdeaux, Talence Cedex, France

Centre hospitalier universitaire Toulouse (CHU Toulouse)

Toulouse, Toulouse, France

Hospital Universitari Vall D'Hebron

Barcelona, Catalonia, Spain

Centre hospitalier universitaire vaudois (CHUV)

Lausanne, Canton of Vaud, Switzerland

Outcomes

Primary Outcomes

Viral load decay

Differences in log CMV viral load in plasma between baseline and 3 weeks

Time frame: 3 weeks

Secondary Outcomes

Change in CMV-specific immune signature score

Change in the CMV-specific immune signature from baseline to week 3 and week 8, assessed using a predefined composite immune monitoring panel derived from the HORUS cohort. The panel will include CMV-specific T-cell functional assays and phenotyping, such as quantitative and qualitative measures of CD4 and CD8 CMV-specific responses, cytokine production, and selected activation/exhaustion markers. Results will be summarized as change from baseline at each time point.

Time frame: from enrollment to 3 and 8 weeks

Viral load decay according to immune signature

Difference in log CMV viral load decay between baseline and 3 and 8 weeks according to baseline immune signature

Time frame: 3 and 8 weeks