Health TrialsbyHealthPanel

HORUS-Cytomegalovirus Open Proof-of-concept Exploratory Trial

ConditionCMV Infection
Trial statusNot yet recruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexAll
Age18+
SponsorOriol Manuel

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Disqualifiers

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.

Trial design

Design model

Parallel

Treatments tested in this trial

  • 50% reduction in the dose of MPA

    Drug

    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 tacrolimus

    Drug

    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)

Treatment groups

100 Participants
are divided into 3 treatment groups
Group A: 50% reduction in the dose of MPA for a duration of minimum 21 daysExperimental treatment 1 intervention
Group B: switch of MPA to everolimus with adapted dose of tacrolimus, for a duration of at least 56 daysExperimental treatment 1 intervention
Group C: Standard antiviral therapy without modulation of immunosuppressionActive comparator 1 intervention

Trial outcomes

Primary outcomes

1

Viral load decay

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

Time frame
3 weeks

Secondary outcomes

1

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
2

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

Other outcomes

1

Viral load decay

Differences in log CMV viral load in plasma between baseline and 8 weeks

Time frame
8 weeks
2

Viral load eradication

Rate of patients with CMV viral load eradication, defined as the percentage of patients with a CMV PCR result below the level of quantification at 3 weeks and 8 weeks

Time frame
3 and 8 weeks
3

Refractory CMV infection

Rate of refractory CMV infection at 8 weeks, according to standard definition

Time frame
8 weeks
4

Safety outcome 1

Episodes of biopsy-proven acute rejection within 90 days

Time frame
90 days

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Oriol Manuel

Lead sponsor

University of Lausanne Hospitals

Sponsor institution

Centre Hospitalier Universitaire Bordeaux

Collaborator

Centre Hospitalier Universitaire de Toulouse, FRANCE

Collaborator

Hospital Vall d'Hebron

Collaborator

Source ClinicalTrials.gov

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