HORUS-Cytomegalovirus Open Proof-of-concept Exploratory Trial (HORUS-COPE)
29 april 2026 uppdaterad av: Oriol Manuel
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.
Studieöversikt
Status
Har inte rekryterat ännu
Betingelser
Detaljerad beskrivning
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:
- 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])
- a switch from MPA to a mammalian target of rapamycin inhibitor (mTORi) everolimus, together with an adapted dose of tacrolimus.
Studietyp
Interventionell
Inskrivning (Beräknad)
100
Fas
- Fas 4
Kontakter och platser
Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.
Studiekontakt
- Namn: Oriol Manuel, Professor, MD
- Telefonnummer: +41 79 556 61 36
- E-post: oriol.manuel@chuv.ch
Studera Kontakt Backup
- Namn: Elisa Ruiz-Arabi, MD, PhD
- Telefonnummer: +41 79 556 5484
- E-post: elisa.ruiz-arabi@chuv.ch
Studieorter
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Talence Cedex
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Bourdeaux, Talence Cedex, Frankrike, 33404
- Centre hospitalier universitaire Bordeaux (CHU Bordeaux)
-
Kontakt:
- Hannah Kaminski, Professor, MD, PhD
- Telefonnummer: +33 05 56 79 56 79
- E-post: hannah.kaminski@chu-bordeaux.fr
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Underutredare:
- Lionel Couzi, Professor MD, PhD
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Toulouse
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Toulouse, Toulouse, Frankrike, 31059
- Centre hospitalier universitaire Toulouse (CHU Toulouse)
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Kontakt:
- Nassim Kamar, Professor, MD, PhD
- Telefonnummer: +33 05 61 77 22 33
- E-post: kamar.n@chu-toulouse.fr
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Canton of Vaud
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Lausanne, Canton of Vaud, Schweiz, 1011
- Centre Hospitalier Universitaire Vaudois (CHUV)
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Kontakt:
- Oriol Manuel, Professor, MD
- Telefonnummer: +41 79 556 61 36
- E-post: oriol.manuel@chuv.ch
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Kontakt:
- Elisa Ruiz-Arabi, MD, PhD
- Telefonnummer: +41 79 556 5484
- E-post: elisa.ruiz-arabi@chuv.ch
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Underutredare:
- Dela Golshayan, Professor, MD PhD
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Underutredare:
- Julien Vionnet, MD, PhD
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Underutredare:
- Patrick Yerly, MD
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Catalonia
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Barcelona, Catalonia, Spanien, 08035
- Hospital Universitari Vall d'Hebron
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Kontakt:
- Oriol Bestard, MD PhD
- Telefonnummer: +34 934 893 000
- E-post: oriol.bestard@vallhebron.cat
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Deltagandekriterier
Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.
Urvalskriterier
Åldrar som är berättigade till studier
- Vuxen
- Äldre vuxen
Tar emot friska volontärer
Nej
Beskrivning
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).
Studieplan
Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Behandling
- Tilldelning: Randomiserad
- Interventionsmodell: Parallellt uppdrag
- Maskning: Ingen (Open Label)
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
|---|---|
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Experimentell: 50% reduction in the dose of MPA for a duration of minimum 21 days
with standard antiviral therapy
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50% reduction in the dose of MPA with standard antiviral therapy
Andra namn:
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Experimentell: switch of MPA to everolimus with adapted dose of tacrolimus, for a duration of at least 56 days
with standard antiviral therapy
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Switch from MPA to a mammalian target of rapamycin inhibitor (mTORi), together with an adapted dose of tacrolimus, with standard antiviral therapy
Andra namn:
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Aktiv komparator: Standard antiviral therapy without modulation of immunosuppression
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standard antiviral therapy along with maintenance of their initial immunosuppressive therapy (control group)
Andra namn:
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Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
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Viral load decay
Tidsram: 3 weeks
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Differences in log CMV viral load in plasma between baseline and 3 weeks
|
3 weeks
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Sekundära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
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Change in CMV-specific immune signature score
Tidsram: from enrollment to 3 and 8 weeks
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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.
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from enrollment to 3 and 8 weeks
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Viral load decay according to immune signature
Tidsram: 3 and 8 weeks
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Difference in log CMV viral load decay between baseline and 3 and 8 weeks according to baseline immune signature
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3 and 8 weeks
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Andra resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
|
Viral load decay
Tidsram: 8 weeks
|
Differences in log CMV viral load in plasma between baseline and 8 weeks
|
8 weeks
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Viral load eradication
Tidsram: 3 and 8 weeks
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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
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3 and 8 weeks
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Refractory CMV infection
Tidsram: 8 weeks
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Rate of refractory CMV infection at 8 weeks, according to standard definition
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8 weeks
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Safety outcome 1
Tidsram: 90 days
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Episodes of biopsy-proven acute rejection within 90 days
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90 days
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Safety Outcome 2
Tidsram: 90 days
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Delta eGFR ml/min between baseline and day 90
|
90 days
|
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Safety Outcome 3
Tidsram: 90 days
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mTORi /MPA toxicity
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90 days
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Samarbetspartners och utredare
Det är här du hittar personer och organisationer som är involverade i denna studie.
Sponsor
Samarbetspartners
Utredare
- Huvudutredare: Oriol Manuel, Professor, MD, Service des maladies infectieuses, Centre hospitalier universitaire vaudois (CHUV)
Publikationer och användbara länkar
Den som ansvarar för att lägga in information om studien tillhandahåller frivilligt dessa publikationer. Dessa kan handla om allt som har med studien att göra.
Allmänna publikationer
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Användbara länkar
Studieavstämningsdatum
Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.
Studera stora datum
Studiestart (Beräknad)
1 april 2026
Primärt slutförande (Beräknad)
1 januari 2028
Avslutad studie (Beräknad)
1 mars 2028
Studieregistreringsdatum
Först inskickad
23 april 2026
Först inskickad som uppfyllde QC-kriterierna
29 april 2026
Första postat (Faktisk)
6 maj 2026
Uppdateringar av studier
Senaste uppdatering publicerad (Faktisk)
6 maj 2026
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
29 april 2026
Senast verifierad
1 april 2026
Mer information
Termer relaterade till denna studie
Nyckelord
Ytterligare relevanta MeSH-villkor
- Virussjukdomar
- DNA-virusinfektioner
- Herpesviridae-infektioner
- Infektioner
- Cytomegalovirusinfektioner
- Organiska kemikalier
- Undersökningstekniker
- Epidemiologisk forskningsdesign
- Epidemiologiska metoder
- Forskningsdesign
- Metoder
- Fettsyror
- Lipider
- Syror, acykliska
- Karboxylsyror
- Makrolider
- Laktoner
- Sirolimus
- Caproates
- Everolimus
- Mykofenolsyra
- Kontrollgrupper
Andra studie-ID-nummer
- 2025-02457
- 2025-524845-28-00 (Ctis)
- HumRes (Registeridentifierare: BASEC 2025-02457)
Plan för individuella deltagardata (IPD)
Planerar du att dela individuella deltagardata (IPD)?
JA
IPD-planbeskrivning
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.
IPD-delning som stöder informationstyp
- STUDY_PROTOCOL
- SAV
- ANALYTIC_CODE
- CSR
Läkemedels- och apparatinformation, studiedokument
Studerar en amerikansk FDA-reglerad läkemedelsprodukt
Nej
Studerar en amerikansk FDA-reglerad produktprodukt
Nej
produkt tillverkad i och exporterad från U.S.A.
Nej
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