Cytomegalovirus InfectionPhase 3LUCY-1NCT06334497
Letermovir-based Dual Therapy for Treatment of Cytomegalovirus Infections
A Phase 3 study testing Letermovir and Valganciclovir in people with Cytomegalovirus Infection, run by Assistance Publique - Hôpitaux de Paris at 5 sites in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cytomegalovirus Infection
- What is being tested?
- Letermovir and Valganciclovir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 5 sitesFrance
- Study dates
- 14 Aug 2024to Nov 2027
- Phase
- Phase 3
- 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
- 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).
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- 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
Who cannot join
- 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)
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- Have a known human immunodeficiency virus (HIV) infection with plasma HIV RNA ≥ 50 copies/mL within the 3 months before inclusion.
- 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.
- Participation to another clinical trial on medicinal products for human use
- Have an absolute neutrophil count less than 500 cells/µl, or platelet count less than 25,000/µl, or haemoglobin less than 8 g/dl
Trial locations and contacts
5 sites in 1 country. Contact the study team or a site near you to ask about taking part.
5 sites in 1 country
France5 sites, 5 recruiting
- Recruiting
Hôpital Necker Enfants Malades
Paris, 75015
Laurence BUSSIERES, PhD, +33 6 62 08 19 58, laurence.bussieres@aphp.fr
- Recruiting
Hôpital de la Pitié Salpêtrière, Service de Néphrologie
Paris, Île-de-France Region, 75013
Hélène FRANCOIS, 01 42 17 71 14. ext. +33
- Recruiting
Hôpital Européen Georges Pompidou
Paris, Île-de-France Region, 75015
Eric THERVET, MD, PhD, 01 56 60 92 00 00 ext. +33, eric.thervet@aphp.fr
- Recruiting
Hôpital Necker Enfants Malades - SMIT
Paris, Île-de-France Region, 75015
Alexandra SERRIS, 01 42 19 52 62 ext. +33, Alexandra.serris@aphp.fr
- Recruiting
Centre 011-Hôpital Bichat, Service de Néphrologie
Paris, Île-de-France Region, 75018
Christine RANDOUX, 01 40 25 71 01 ext. +33, Christine.randoux@aphp.fr
About this study
Official title: Letermovir/Valganciclovir Combination Versus Valganciclovir Monotherapy for Treatment of Cytomegalovirus (CMV) Infections in Kidney Transplant Recipients
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.
Read the detailed description
Ganciclovir and valganciclovir are the drugs of choice to treat CMV infections and diseases in immunocompromised patients. However, (val)ganciclovir does not seem to be a panacea and its modest efficacy and dose-limiting toxicities limit effectiveness. More, (val)ganciclovir use may drive development of drug-resistant infections, particularly in immunocompromised patients.
An in vitro study suggested additive effects for the combination of letermovir with all approved drugs for treatment or prevention of CMV infections. Investigator's hypothesis is that letermovir plus valganciclovir dual therapy will inhibit CMV replication faster than valganciclovir monotherapy. More, the use of antiviral dual therapy aims to decrease the risk of drug resistance mutations' selection, as previously demonstrated in several other viral infections.
In this study, renal transplant recipients with CMV DNAemia requiring valganciclovir will be randomized to receive either letermovir plus valganciclovir or letermovir placebo plus valganciclovir, until reaching the "treatment success" or the "treatment failure" criteria, up to 12 weeks.
Treatment success will be defined as, from Week-3:
- eradication of CMV DNAemia, defined as CMV DNAemia in whole blood below lower limit of quantification (LLOQ) < 200 IU/mL on 1 blood sample.
- AND resolution of clinical symptoms of CMV disease (if appropriate)
Treatment failure will be defined as fulfilling at least one criterion among:
- failure to achieve a decrease of CMV DNAemia ≥ 1 log10 IU/mL at Week-3 compared to the baseline CMV DNAemia
- persistence of CMV DNAemia ≥ LLOQ (200 IU/ml) at Week-12
- absence of improved CMV disease at Week-3.
- Conditions
- Cytomegalovirus Infection
- Being tested
- Letermovir, Valganciclovir, Letermovir placebo
- Keywords
- Cytomegalovirus infection, Cytomegalovirus disease
- Medical subject headings
- Cytomegalovirus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LetermovirDrug
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.
ValganciclovirDrug
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 placeboDrug
480mg (2X240mg- tablets) of Letermovir placebo given orally once a day until the "treatment success" or the "treatment failure", up to 12 weeks
| Study group | Role | What they receive |
|---|---|---|
| Letermovir+Valganciclovir | Experimental | Daily administration of Letermovir plus Valganciclovir Receives: Drug: Letermovir; Drug: Valganciclovir |
| Letermovir Placebo+Valganciclovir | Active comparator | Daily administration of Letermovir placebo plus Valganciclovir Receives: Drug: Valganciclovir; Drug: Letermovir placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 3 weeks
Secondary outcomes (8)
Eradication of CMV DNAemia (< 200 IU/ml) before Week-12
quantitative CMV PCR performed in whole blood every week until interruption of antiviral treatment, or at the latest until Week-12
Measured: 12 weeks
Number of days between baseline and first measure of CMV DNAemia < 200 IU/mL
Quantitative CMV PCR performed in whole blood every week until interruption of antiviral treatment, or at the latest until Week-12
Measured: 12 weeks
Absence of CMV-related disease or syndrome at baseline and each visit
Measured: 12 weeks
Adverse event (AE) occurence
Clinical examination and clinical laboratory assessments performed every week until interruption of antiviral treatment (or at the latest until Week-12)
Measured: 12 weeks
Sequencing of whole UL97, UL54, UL56, UL89 and UL51 genes
in blood samples at baseline, at Week-3 or Week-12 (in patients achieving criteria defining "treatment failure"), and at any visit in patients presented with rebound of CMV DNAemia
Measured: 12 weeks
Ganciclovir plasma concentration
at Week-1 and Week-2, in case of premature termination of treatment for any reason or premature exit from the study.
Measured: 2 weeks
Letermovir plasma concentration
t Week-1 and Week-2, in case of premature termination of treatment for any reason or premature exit from the study.
Measured: 2 weeks
Measure of the CMV specific T-cell immunity
at baseline, Week-3, Week-6, Week-9 and Week-12.
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Mar 2024
- Study start14 Aug 2024
- Primary completionSep 2027 (estimated)
- Study completionNov 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cytomegalovirus InfectionStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- URC-CIC Paris Descartes Necker Cochin
- Responsible party
- Sponsor
- Investigators
- Marianne LERUEZ-VILLE, MD, PhD, Study chair, Virology laboratory- reference national Lab for CMV infection -Hôpital Necker Enfants malades, ParisPierre FRANGE, MD, PhD, Principal investigator, Assistance Publique Hôpitaux Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06334497
- Sponsor's protocol ID
- APHP220791
- Other IDs
- 2023-506216-40-00, 2023
- Acronym
- LUCY-1
- Status last verified
- Dec 2025
- First submitted
- 15 Feb 2024
- Last updated
- 2 Jan 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Letermovir/Valganciclovir Combination Versus Valganciclovir Monotherapy for Treatment of Cytomegalovirus (CMV) Infections in Kidney Transplant Recipients
- ClinicalTrials.gov ID
- NCT06334497
- Acronym / sponsor ID
- LUCY-1 / APHP220791
- Conditions
- Cytomegalovirus Infection
- Keywords
- Cytomegalovirus infection, Cytomegalovirus disease
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- URC-CIC Paris Descartes Necker Cochin
- Study start
- 14 Aug 2024 (actual)
- Primary completion
- Sep 2027 (estimated)
- Study completion
- Nov 2027 (estimated)
- First posted
- 28 Mar 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Ganciclovir and valganciclovir are the drugs of choice to treat CMV infections and diseases in immunocompromised patients. However, (val)ganciclovir does not seem to be a panacea and its modest efficacy and dose-limiting toxicities limit effectiveness. More, (val)ganciclovir use may drive development of drug-resistant infections, particularly in immunocompromised patients.
An in vitro study suggested additive effects for the combination of letermovir with all approved drugs for treatment or prevention of CMV infections. Investigator's hypothesis is that letermovir plus valganciclovir dual therapy will inhibit CMV replication faster than valganciclovir monotherapy. More, the use of antiviral dual therapy aims to decrease the risk of drug resistance mutations' selection, as previously demonstrated in several other viral infections.
In this study, renal transplant recipients with CMV DNAemia requiring valganciclovir will be randomized to receive either letermovir plus valganciclovir or letermovir placebo plus valganciclovir, until reaching the "treatment success" or the "treatment failure" criteria, up to 12 weeks.
Treatment success will be defined as, from Week-3:
- eradication of CMV DNAemia, defined as CMV DNAemia in whole blood below lower limit of quantification (LLOQ) < 200 IU/mL on 1 blood sample.
- AND resolution of clinical symptoms of CMV disease (if appropriate)
Treatment failure will be defined as fulfilling at least one criterion among:
- failure to achieve a decrease of CMV DNAemia ≥ 1 log10 IU/mL at Week-3 compared to the baseline CMV DNAemia
- persistence of CMV DNAemia ≥ LLOQ (200 IU/ml) at Week-12
- absence of improved CMV disease at Week-3.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Letermovir+Valganciclovir | Experimental | Drug: Letermovir, Drug: ValganciclovirDaily administration of Letermovir plus Valganciclovir |
| Letermovir Placebo+Valganciclovir | Active comparator | Drug: Valganciclovir, Drug: Letermovir placeboDaily administration of Letermovir placebo plus Valganciclovir |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Letermovir480mg (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. | Drug | Letermovir+Valganciclovir |
| ValganciclovirValganciclovir 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. | Drug | Letermovir Placebo+Valganciclovir, Letermovir+Valganciclovir |
| Letermovir placebo480mg (2X240mg- tablets) of Letermovir placebo given orally once a day until the "treatment success" or the "treatment failure", up to 12 weeks | Drug | Letermovir Placebo+Valganciclovir |
Primary outcome
Virological response to treatment on week-3
Time frame: 3 weeks
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
8 secondary outcomes
Eradication of CMV DNAemia (< 200 IU/ml) before Week-12
Time frame: 12 weeks
Number of days between baseline and first measure of CMV DNAemia < 200 IU/mL
Time frame: 12 weeks
Absence of CMV-related disease or syndrome at baseline and each visit
Time frame: 12 weeks
Adverse event (AE) occurence
Time frame: 12 weeks
Sequencing of whole UL97, UL54, UL56, UL89 and UL51 genes
Time frame: 12 weeks
Ganciclovir plasma concentration
Time frame: 2 weeks
Letermovir plasma concentration
Time frame: 2 weeks
Measure of the CMV specific T-cell immunity
Time frame: 12 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jan 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Marianne LERUEZ-VILLE, MD, PhD study chair
Virology laboratory- reference national Lab for CMV infection -Hôpital Necker Enfants malades, Paris
Pierre FRANGE, MD, PhD principal investigator
Assistance Publique Hôpitaux Paris
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Letermovir and Valganciclovir in people with Cytomegalovirus Infection, run by Assistance Publique - Hôpitaux de Paris at 5 sites in France.
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 11 inclusion and 18 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: looking for participants now, as of the sponsor's last update on 2 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in France. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 Pierre FRANGE, MD, PhD (+33 1.44.49.49.61, pierre.frange@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Virological response to treatment on week-3 (time frame: 3 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 2 Jan 2026.