HORUS-Cytomegalovirus Open Proof-of-concept Exploratory Trial

ClinicalTrials.gov ID

NCT07570433

Lead Sponsor

Oriol ManuelOTHER

Overall Status

Not yet recruiting

Study Type

Interventional

Phase

Phase 4

Enrollment

100Estimated

Last Update Posted

May 6, 2026Actual

Start Date

Apr 2026Estimated

Primary Completion Date

Jan 2028Estimated

Completion Date

Mar 2028Estimated

Official Title

HORUS-Cytomegalovirus Open Proof-of-concept Exploratory Trial (HORUS-COPE): An International Proof-of-concept Clinical Trial on Modulation of Immunosuppressive Regimen in Solid-organ Transplant Recipients With Cytomegalovirus Infection.

Brief Summary

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 to dynamically estimate the risk of CMV replication. This approach allows for the individualization of preventive and therapeutic strategies, improving patient outcomes.

The HORUS-COPE trial is 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.

Detailed Description

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.

• CMV Infection

• 50% reduction in the dose of MPA
• Switch from MPA to a mammalian target of rapamycin inhibitor (mTORi), together with an adapted dose of tacrolimus
• standard antiviral therapy along with maintenance of their initial immunosuppressive therapy.

Ages Eligible for Study

Adult (18-64)Older Adult (65+)

Sexes Eligible for Study

All

Accepts Healthy Volunteers

No

Eligibility Criteria

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).

Primary Purpose

Treatment

Allocation

Randomized

Interventional Model

Parallel Assignment

Masking

None (Open Label)

Lead Sponsor

Oriol ManuelOTHER

Collaborators

Centre Hospitalier Universitaire BordeauxUNKNOWN

Centre Hospitalier Universitaire de Toulouse, FRANCEUNKNOWN

Hospital Vall d'HebronOTHER

kamar.n@chu-toulouse.fr+33 05 61 77 22 33

oriol.bestard@vallhebron.cat+34 934 893 000

oriol.manuel@chuv.ch+41 79 556 61 36

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