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CMV InfectionPhase 4HORUS-COPENCT07570433

HORUS-Cytomegalovirus Open Proof-of-concept Exploratory Trial

A Phase 4 study testing 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 and standard antiviral therapy along with maintenance of their initial immunosuppressive therapy. in people with CMV Infection, run by Oriol Manuel at 4 sites in 3 countries.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
CMV Infection
What is being tested?
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 and standard antiviral therapy along with maintenance of their initial immunosuppressive therapy.
Could I receive a placebo?
No, everyone receives an active treatment
How many people
100 participants
Where
4 sitesin 3 countries
Study dates
Apr 2026to Mar 2028
Phase
Phase 4
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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).

Trial locations and contacts

4 sites in 3 countries. Contact the study team or a site near you to ask about taking part.

Oriol Manuel, Professor, MD contact

+41 79 556 61 36

oriol.manuel@chuv.ch

Elisa Ruiz-Arabi, MD, PhD contact

+41 79 556 5484

elisa.ruiz-arabi@chuv.ch

4 sites in 3 countries

France2 sites

  • Centre hospitalier universitaire Bordeaux (CHU Bordeaux)

    Bourdeaux, Talence Cedex, 33404

    Hannah Kaminski, Professor, MD, PhD, +33 05 56 79 56 79, hannah.kaminski@chu-bordeaux.fr

    Lionel Couzi, Professor MD, PhD

  • Centre hospitalier universitaire Toulouse (CHU Toulouse)

    Toulouse, Toulouse, 31059

    Nassim Kamar, Professor, MD, PhD, +33 05 61 77 22 33, kamar.n@chu-toulouse.fr

Other trials in France

Spain1 site

  • Hospital Universitari Vall D'Hebron

    Barcelona, Catalonia, 08035

    Oriol Bestard, MD PhD, +34 934 893 000, oriol.bestard@vallhebron.cat

Other trials in Spain

Switzerland1 site

  • Centre hospitalier universitaire vaudois (CHUV)

    Lausanne, Canton of Vaud, 1011

    Oriol Manuel, Professor, MD, +41 79 556 61 36, oriol.manuel@chuv.ch

    Elisa Ruiz-Arabi, MD, PhD, +41 79 556 5484, elisa.ruiz-arabi@chuv.ch

Other trials in Switzerland

About this study

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.

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.

Read the 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.
Conditions
CMV Infection
Being tested
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.
Keywords
solid organ transplantation, CMV, cytomegalovirus, immunosuppression, everolimus, mTORi, MPA, infection, immune signature
Medical subject headings
Cytomegalovirus Infections, Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 50% reduction in the dose of MPADrug

    Also called Mycophenolic acid, Mycophenolate mofetil

    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

    Also called everolimus

    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

    Also called control group

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

Study groups in NCT07570433
Study groupRoleWhat they receive
50% reduction in the dose of MPA for a duration of minimum 21 daysExperimentalwith standard antiviral therapy
Receives: Drug: 50% reduction in the dose of MPA
switch of MPA to everolimus with adapted dose of tacrolimus, for a duration of at least 56 daysExperimentalwith standard antiviral therapy
Receives: Drug: Switch from MPA to a mammalian target of rapamycin inhibitor (mTORi), together with an adapted dose of tacrolimus
Standard antiviral therapy without modulation of immunosuppressionActive comparatorNot described
Receives: Drug: standard antiviral therapy along with maintenance of their initial immunosuppressive therapy.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Viral load decay

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

    Measured: 3 weeks

Secondary outcomes (2)

  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.

    Measured: 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

    Measured: 3 and 8 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 May 2026
  2. Study startApr 2026 (estimated)
  3. Primary completionJan 2028 (estimated)
  4. Study completionMar 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Randomized open-label, phase IV non-comparative trial with three parallel arms
Masking
None (open label)
Enrolment
100 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07570433
Sponsor's protocol ID
2025-02457
Other IDs
2025-524845-28-00, HumRes, 2025
Acronym
HORUS-COPE
Status last verified
Apr 2026
First submitted
23 Apr 2026
Last updated
6 May 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: After the study is completed, de-identified individual participant data may be shared. Data will be made available only after a formal request to the Principal Investigator (PI) and approval by the study's Scientific Committee. Data sharing will be limited to use for scientific research purposes and will follow all applicable privacy and ethical regulations.

Publications

  • Qazi Y, Shaffer D, Kaplan B, Kim DY, Luan FL, Peddi VR, Shihab F, Tomlanovich S, Yilmaz S, McCague K, Patel D, Mulgaonkar S. Efficacy and Safety of Everolimus Plus Low-Dose Tacrolimus Versus Mycophenolate Mofetil Plus Standard-Dose Tacrolimus in De Novo Renal Transplant Recipients: 12-Month Data. Am J Transplant. 2017 May;17(5):1358-1369. doi: 10.1111/ajt.14090. Epub 2017 Jan 4.

    PubMed 27775865

  • Viana LA, Cristelli MP, Basso G, Santos DW, Dantas MTC, Dreige YC, Requiao Moura LR, Nakamura MR, Medina-Pestana J, Tedesco-Silva H. Conversion to mTOR Inhibitor to Reduce the Incidence of Cytomegalovirus Recurrence in Kidney Transplant Recipients Receiving Preemptive Treatment: A Prospective, Randomized Trial. Transplantation. 2023 Aug 1;107(8):1835-1845. doi: 10.1097/TP.0000000000004559. Epub 2023 Jul 20.

    PubMed 37046380

  • Kaminski H, Kamar N, Thaunat O, Bouvier N, Caillard S, Garrigue I, Anglicheau D, Rerolle JP, Le Meur Y, Durrbach A, Bachelet T, Savel H, Coueron R, Visentin J, Del Bello A, Pellegrin I, Dechanet-Merville J, Merville P, Thiebaut R, Couzi L. Incidence of cytomegalovirus infection in seropositive kidney transplant recipients treated with everolimus: A randomized, open-label, multicenter phase 4 trial. Am J Transplant. 2022 May;22(5):1430-1441. doi: 10.1111/ajt.16946. Epub 2022 Jan 19.

    PubMed 34990047

  • Kaminski H, Marseres G, Yared N, Nokin MJ, Pitard V, Zouine A, Garrigue I, Loizon S, Capone M, Gauthereau X, Mamani-Matsuda M, Coueron R, Duran RV, Pinson B, Pellegrin I, Thiebaut R, Couzi L, Merville P, Dechanet-Merville J. mTOR Inhibitors Prevent CMV Infection through the Restoration of Functional alphabeta and gammadelta T cells in Kidney Transplantation. J Am Soc Nephrol. 2022 Jan;33(1):121-137. doi: 10.1681/ASN.2020121753. Epub 2021 Nov 1.

    PubMed 34725108

  • Poglitsch M, Weichhart T, Hecking M, Werzowa J, Katholnig K, Antlanger M, Krmpotic A, Jonjic S, Horl WH, Zlabinger GJ, Puchhammer E, Saemann MD. CMV late phase-induced mTOR activation is essential for efficient virus replication in polarized human macrophages. Am J Transplant. 2012 Jun;12(6):1458-68. doi: 10.1111/j.1600-6143.2012.04002.x. Epub 2012 Mar 5.

    PubMed 22390651

  • Clippinger AJ, Maguire TG, Alwine JC. The changing role of mTOR kinase in the maintenance of protein synthesis during human cytomegalovirus infection. J Virol. 2011 Apr;85(8):3930-9. doi: 10.1128/JVI.01913-10. Epub 2011 Feb 9.

    PubMed 21307192

  • Asberg A, Jardine AG, Bignamini AA, Rollag H, Pescovitz MD, Gahlemann CC, Humar A, Hartmann A; VICTOR Study Group. Effects of the intensity of immunosuppressive therapy on outcome of treatment for CMV disease in organ transplant recipients. Am J Transplant. 2010 Aug;10(8):1881-8. doi: 10.1111/j.1600-6143.2010.03114.x. Epub 2010 May 10.

    PubMed 20486914

  • Dubrawka CA, Progar KJ, January SE, Hagopian JC, Nesselhauf NM, Malone AF. Impact of antimetabolite discontinuation following cytomegalovirus or BK polyoma virus infection in kidney transplant recipients. Transpl Infect Dis. 2022 Dec;24(6):e13931. doi: 10.1111/tid.13931. Epub 2022 Aug 26.

    PubMed 35980197

  • Kaminski H, Garrigue I, Couzi L, Taton B, Bachelet T, Moreau JF, Dechanet-Merville J, Thiebaut R, Merville P. Surveillance of gammadelta T Cells Predicts Cytomegalovirus Infection Resolution in Kidney Transplants. J Am Soc Nephrol. 2016 Feb;27(2):637-45. doi: 10.1681/ASN.2014100985. Epub 2015 Jun 8.

    PubMed 26054538

  • Bestard O, Kaminski H, Couzi L, Fernandez-Ruiz M, Manuel O. Cytomegalovirus Cell-Mediated Immunity: Ready for Routine Use? Transpl Int. 2023 Nov 7;36:11963. doi: 10.3389/ti.2023.11963. eCollection 2023.

    PubMed 38020746

  • Kotton CN, Kumar D, Manuel O, Chou S, Hayden RT, Danziger-Isakov L, Asberg A, Tedesco-Silva H, Humar A; Transplantation Society International CMV Consensus Group. The Fourth International Consensus Guidelines on the Management of Cytomegalovirus in Solid Organ Transplantation. Transplantation. 2025 Jul 1;109(7):1066-1110. doi: 10.1097/TP.0000000000005374. Epub 2025 Apr 9. No abstract available.

    PubMed 40200403

  • Manuel O, Kralidis G, Mueller NJ, Hirsch HH, Garzoni C, van Delden C, Berger C, Boggian K, Cusini A, Koller MT, Weisser M, Pascual M, Meylan PR; Swiss Transplant Cohort Study. Impact of antiviral preventive strategies on the incidence and outcomes of cytomegalovirus disease in solid organ transplant recipients. Am J Transplant. 2013 Sep;13(9):2402-10. doi: 10.1111/ajt.12388. Epub 2013 Aug 5.

    PubMed 23914796

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing 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 and standard antiviral therapy along with maintenance of their initial immunosuppressive therapy. in people with CMV Infection, run by Oriol Manuel at 4 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 6 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in France, Spain, Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Oriol Manuel, Professor, MD (+41 79 556 61 36, oriol.manuel@chuv.ch), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Viral load decay (time frame: 3 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07570433, which also lists 12 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2026.

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