Letermovir-based Dual Therapy for Treatment of Cytomegalovirus Infections

NCT06334497 | Recruiting Phase 3

• 2 other identifiers: APHP2207912023-506216-40-00
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 5

Brief Summary

The purpose of this study is to evaluate the efficacy and the tolerance of letermovir as part of dual antiviral therapy (in association with valganciclovir) in renal transplant recipients with CMV DNAemia, requiring valganciclovir treatment per investigator's judgment.

Conditions

Cytomegalovirus Infection

Keywords

Cytomegalovirus infection; Cytomegalovirus disease

Outcome Measures

Primary Outcomes (1)

• Virological response to treatment on week-3

  defined as a ≥ 2 log10 decrease of CMV DNAemia in whole blood from baseline, or an undetectable CMV DNAemia (\< 200 IU/mL) in whole blood

  3 weeks

Secondary Outcomes (8)

• Eradication of CMV DNAemia (< 200 IU/ml) before Week-12

  12 weeks

• Number of days between baseline and first measure of CMV DNAemia < 200 IU/mL

  12 weeks

• Absence of CMV-related disease or syndrome at baseline and each visit

  12 weeks

• Adverse event (AE) occurence

  12 weeks

• Sequencing of whole UL97, UL54, UL56, UL89 and UL51 genes

  12 weeks

Study Arms (2)

Letermovir+Valganciclovir

EXPERIMENTAL

Daily administration of Letermovir plus Valganciclovir

Drug: Letermovir; Drug: Valganciclovir

Letermovir Placebo+Valganciclovir

ACTIVE COMPARATOR

Daily administration of Letermovir placebo plus Valganciclovir

Drug: Valganciclovir; Drug: Letermovir placebo

Interventions

Letermovir DRUG

480mg (2X240mg- tablets) of Letermovir given orally once a day until the "treatment success" or the "treatment failure", up to 12 weeks. In case of co-administration with cyclosporine A, the dosage of Letermovir will be reduced.

Letermovir+Valganciclovir

Valganciclovir DRUG

Valganciclovir 900 mg (2X450 mg-tablets) twice a day until the "treatment success" or the "treatment failure", up to 12 weeks. In case of impaired renal function, the dosage of valganciclovir will be reduced.

Letermovir Placebo+Valganciclovir; Letermovir+Valganciclovir

Letermovir placebo DRUG

480mg (2X240mg- tablets) of Letermovir placebo given orally once a day until the "treatment success" or the "treatment failure", up to 12 weeks

Letermovir Placebo+Valganciclovir

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• Weight ≥ 30 kg
• Kidney transplant recipient
• Have a documented CMV infection or disease, with (i) a screening value of CMV DNA ≥ 3000 IU/mL in whole blood or plasma in 2 consecutive assessments separated by ≥ 1 day, as determined by local laboratory quantitative polymerase chain reaction (qPCR). Both samples should be taken within 14 days prior to randomization with the second sample obtained within 5 days prior to randomization OR (ii) a screening value of CMV DNA ≥ 30000 IU/mL in whole blood or plasma, as determined by local laboratory quantitative polymerase chain reaction (qPCR), in 1 sample obtained within 5 days prior to randomization
• Eligible for treatment with oral valganciclovir, per investigator's judgment
• For patients of childbearing age (following menarche): negative bHCG and effective method of contraception (sexual abstinence, hormonal contraception containing ethinylestradiol and levonorgestrel, intrauterine device or hormone-releasing system, cap, diaphragm or sponge with spermicide, condom) until 30 days after the end of relevant systemic exposure (week 13).
• For male an effective method of contraception (sexual abstinence, condom) until 90 days after the end of relevant systemic exposure (week 13).
• Have life expectancy of ≥ 8 weeks
• French speaking
• Affiliated to social security regime or an equivalent system
• Informed consent and signed

You may not qualify if:

• Have a current CMV infection that is considered refractory or resistant due to inadequate adherence to antiviral treatment, to the best knowledge of the investigator.
• Have a CMV infection that is known to be genotypically resistant to valganciclovir and/or letermovir on documented evidence.
• Be on treatment with anti-CMV agents (ganciclovir, valganciclovir, foscarnet, cidofovir, letermovir or maribavir) for the current CMV infection for longer than 72 hours. However, patients experiencing CMV infection while receiving ganciclovir or valganciclovir prophylaxis (i.e. at prophylactic dosages) or letermovir prophylaxis can be included.
• Have an eGFR \< 15 mL/min/1.73m² (using the CKD-EPI Creatinine Equation (2009)).
• Have serum aspartate aminotransferase (AST) ≥ 5 times higher than the upper limit of normal (ULN), or serum alanine aminotransferase (ALT) ≥ 5 times the ULN, or total bilirubin ≥ 3 times the ULN (except for documented Gilbert's syndrome). Note: Subjects with biopsy confirmed CMV hepatitis will not be excluded from study participation despite AST or ALT ≥ 5 times ULN
• Have a severe chronic liver disease (Child-Pugh Class C)
• Require mechanical ventilation or vasopressors for hemodynamic support.
• Be pregnant or breastfeeding.
• Have received anti-CMV vaccine at any time.
• Be receiving leflunomide or artesunate when study treatment is initiated.
• Be receiving strong inhibitors or inducers of hepatic CYP enzymes including rifampicin, phenytoin, clarithromycin, ritonavir, or cobicistat or St. John's wort (Hypericum perforatum) when study treatment is initiated.
• Be receiving efavirenz, etravirine, nevirapine, lopinavir, pimozine, ergot alkaloids, dabigatran, atorvastatine (at a daily dose \> 20mg, and / or if co-administered with cyclosporin A), pravastatin ( if co-administered with cyclosporin A), simvastatine, rosuvastatine, pitavastatine or imipenem-cilastatine when study treatment is initiated.
• Have known hereditary intolerance to galactose, with lactose Lapp deficiency, glucose or galactose malabsorption syndrome.
• Have known hypersensitivity to letermovir or to an excipient for a study treatment.
• Have any clinically significant medical or surgical condition that in the investigator's opinion could interfere with the interpretation of study results, contraindicate the administration of the assigned study treatment, or compromise the safety or well-being of the subject.

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• URC-CIC Paris Descartes Necker Cochin: collaborator

Study Sites (5)

Hôpital Necker Enfants Malades

Paris, 75015, France

RECRUITING

Hôpital de la Pitié Salpêtrière, Service de Néphrologie

Paris, Île-de-France Region, 75013, France

RECRUITING

Hôpital Européen Georges Pompidou

Paris, Île-de-France Region, 75015, France

RECRUITING

Hôpital Necker Enfants Malades - SMIT

Paris, Île-de-France Region, 75015, France

RECRUITING

Centre 011-Hôpital Bichat, Service de Néphrologie

Paris, Île-de-France Region, 75018, France

RECRUITING

MeSH Terms

Conditions

Cytomegalovirus Infections

Interventions

letermovir; Valganciclovir

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections

Intervention Hierarchy (Ancestors)

Ganciclovir; Acyclovir; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Marianne LERUEZ-VILLE, MD, PhD

  Virology laboratory- reference national Lab for CMV infection -Hôpital Necker Enfants malades, Paris

  STUDY CHAIR

• Pierre FRANGE, MD, PhD

  Assistance Publique Hôpitaux Paris

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Pierre FRANGE, MD, PhD

CONTACT

+33 1.44.49.49.61; pierre.frange@aphp.fr

Aminata TRAORE

CONTACT

+33 1.42.19.27.34; aminata.traore@aphp.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 15, 2024
• First Posted: March 28, 2024
• Study Start: August 14, 2024
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): November 1, 2027
• Last Updated: January 2, 2026

Record last verified: 2025-12

Locations

FR (5)