CMVPhase 4CLEAR-CMVNCT07235683
Combination Letermovir and Standard of Care Antiviral for Enhanced Antiviral Response in Cytomegalovirus Infection in Lung Transplant Recipients
A Phase 4 study testing Letermovir and Valganciclovir/Ganciclovir in people with CMV and Lung Transplant Recipient, run by University Health Network, Toronto at 1 site in Canada.
Trial summary
The primary objective of the CLEAR-CMV trial is to evaluate the efficacy of letermovir therapy plus standard of care (SOC) antiviral compared to SOC plus placebo in achieving clearance of CMV viremia by week 3 in lung transplant recipients with active CMV infection. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- CMV, Lung Transplant Recipient
- What is being tested?
- Letermovir and Valganciclovir/Ganciclovir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteCanada
- Study dates
- 24 Dec 2025to Aug 2027
- 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
- Recipient of a lung transplant.
- Has confirmed CMV viremia with a viral load ≥ 1000 IU/mL and will receive or has just started SOC antiviral treatment in the past 72h as per the decision of the treating physician.
Who cannot join
- Renal failure with Creatinine clearance <15 mL/min or requiring dialysis
- Severe hepatic impairment (Child-Pugh Class C)
- Participating in another interventional clinical trial
- Combined transplant (e.g heart-lung, lung-liver)
- Known allergy or contraindication to any of the antiviral medications
- Known antiviral resistance.
- Patient receiving cyclosporin, pimozide or ergot alkaloids (due to significant drug interaction with letermovir).
- Patient receiving or expected to receive CMV immunoglobulin or IVIG during the initial three week treatment phase
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Canada1 site, 1 recruiting
- Recruiting
University Health Network, Toronto General Hospital
Toronto, Ontario, M5G 2C4
Ilona Bahinskaya, MSc, CCRP, 416-340-4800 ext. 4328, Ilona.Bahinskaya@uhn.ca
About this study
Official title: Combination Letermovir and Standard of Care Antiviral for Enhanced Antiviral Response in Cytomegalovirus Infection in Lung Transplant Recipients: A Pilot Trial
The primary objective of the CLEAR-CMV trial is to evaluate the efficacy of letermovir therapy plus standard of care (SOC) antiviral compared to SOC plus placebo in achieving clearance of CMV viremia by week 3 in lung transplant recipients with active CMV infection.
Read the detailed description
Lung transplant recipients are particularly susceptible to CMV infection due to intensive immunosuppressive regimens required to prevent graft rejection. CMV viremia is associated with increased morbidity, including CMV pneumonitis, and may contribute to chronic lung allograft dysfunction (CLAD).Approximately 30-50% of lung transplant recipients develop CMV infection within the first year post-transplant, with higher rates in CMV-seronegative recipients receiving organs from seropositive donors (D+/R-).
Current standard treatment for CMV infection in transplant recipients involves ganciclovir or its oral prodrug, valganciclovir, which inhibit CMV DNA polymerase. While effective, prolonged use is associated with toxicities, including myelosuppression, and the emergence of resistant strains in some cases. Letermovir, a novel antiviral targeting the CMV terminase complex, has shown efficacy in CMV prophylaxis in hematopoietic stem cell transplant recipients, and in kidney transplant recipients. It has now been extensively studied for use in prophylaxis but there are limited data in treatment. It is an attractive drug in transplant recipients because it has an excellent safety profile and requires no dose adjustment for renal dysfunction. However, data on the use of letermovir for treatment (as opposed to prophylaxis) are more limited. A multicenter study of letermovir use for treatment showed reasonable response rates especially in patients with low viral loads. The use of combination therapy for CMV treatment represents an attractive option, as there is extensive experience with other viruses (e.g. HIV , HCV) to show that this strategy leads to improved response rates and lessens the emergence of antiviral resistance. The use of ganciclovir plus letermovir is attractive because they target two different viral enzymes and both have oral options facilitating outpatient treatment. The most recently published international CMV consensus guidelines reports that the use of combination antiviral therapy is a key research need.
The investigators plan to conduct a pilot trial to determine the efficacy of letermovir plus standard of care (SOC) antiviral therapy in clearing CMV infection. The trial will be conducted in compliance with the protocol, Good Clinical Practices (GCP) and the applicable regulatory requirements.
- Conditions
- CMV, Lung Transplant Recipient
- Being tested
- Letermovir, Placebo, Valganciclovir/Ganciclovir
- Keywords
- CMV Disease, Lung Transplant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LetermovirDrug
Letermovir (480mg) will be given orally as a loading dose every 12 hours for the first 24 hours, then one tablet per day for a total treatment duration of 21 days. Letermovir treatment will be started within 72 hours of starting SOC antiviral treatment as per the decision of the treating physician.
PlaceboDrug
Placebo will be dosed the same as letermovir: one tablet every 12 hours for the first 24 hours, then one tablet per day for total treatment duration of 21 days.
Valganciclovir/GanciclovirDrug
Ganciclovir or its oral prodrug, valganciclovir will be administered as the standard of care antiviral therapy. Its duration will be at the discretion of the treatment physician but is typically given until clearance of viremia. The clinical definition of viral clearance is one negative viral load or two viral loads one week apart that are <200 IU/mL
| Study group | Role | What they receive |
|---|---|---|
| SOC antiviral plus placebo | Placebo comparator | Patients will receive the standard of care (SOC) antiviral therapy along with a placebo drug. The placebo drug will be administered for three weeks, while the SOC antiviral duration and dosage will be at the discretion of the treating physician. Receives: Drug: Placebo; Drug: Valganciclovir/Ganciclovir |
| SOC antiviral plus letermovir active drug | Experimental | Patients will receive the standard of care (SOC) antiviral therapy in combination with letermovir. The letermovir active drug will be administered for three weeks, while the SOC antiviral treatment duration and dosage will be at the discretion of the treating physician. Receives: Drug: Letermovir; Drug: Valganciclovir/Ganciclovir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of patients achieving clearance of CMV viremia by week 3, as measured by quantitative PCR.
Viral clearance is described by a plasma CMV viral load < 200 IU/mL, the UHN clinically used threshold
Measured: From time of enrollment until 3 weeks after enrolment
Secondary outcomes (8)
Proportion of patients achieving an undetectable viral load
The limit of detection for plasma CMV viral load is 35 IU/mL
Measured: At week 3 and by month 6 after enrolment
Proportion of patients achieving CMV viral load <137 IU/mL (lower limit of quantification of the assay)
Lower limit of viral quantitation
Measured: At week 3 from enrolment and at 6 months
Time to clearance of CMV viremia
Clearance of CMV viremia is defined as plasma CMV viral load < 200 IU/mL as measured by quantitative PCR
Measured: From enrolment until clearance of CMV viremia, up to 6 months after enrolment
Time to resolution of symptoms if present
Measured: From enrolment until clearance of symptoms, up to 6 months after enrolment
Development of antiviral resistance
Incidence of antiviral resistance development to letermovir or SOC antivirals at the discretion of the treatment physician
Measured: From enrolment until up to 6 months after enrolment
Incidence of adverse events
Incidence of adverse effects (e.g., myelosuppression, renal dysfunction) will be recorded for the duration of the study.
Measured: From enrolment until up to 6 months after enrolment
Proportion of patients with clinically significant CMV recurrence within 6months, as determined by quantitative PCR or symptomatic CMV disease
Clinically significant CMV recurrence will be determined by a qPCR viral load ≥1000 IU/mL or symptomatic CMV disease
Measured: From enrollment until 6 months.
Monthly enrollment rate as a measure of recruitment feasibility
The investigators will aim for a target enrollment rate of 2 participants per month
Measured: From start of enrollment until up to 6 months after the final patient is enrolled
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Nov 2025
- Study start24 Dec 2025
- Primary completionAug 2027 (estimated)
- Study completionAug 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CMVStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07235683
- Sponsor's protocol ID
- 25-5760
- Acronym
- CLEAR-CMV
- Status last verified
- Feb 2026
- First submitted
- 13 Nov 2025
- Last updated
- 17 Feb 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 17 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combination Letermovir and Standard of Care Antiviral for Enhanced Antiviral Response in Cytomegalovirus Infection in Lung Transplant Recipients: A Pilot Trial
- ClinicalTrials.gov ID
- NCT07235683
- Acronym / sponsor ID
- CLEAR-CMV / 25-5760
- Conditions
- CMV, Lung Transplant Recipient
- Keywords
- CMV Disease, Lung Transplant
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Study start
- 24 Dec 2025 (actual)
- Primary completion
- Aug 2027 (estimated)
- Study completion
- Aug 2027 (estimated)
- First posted
- 19 Nov 2025 (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 primary objective of the CLEAR-CMV trial is to evaluate the efficacy of letermovir therapy plus standard of care (SOC) antiviral compared to SOC plus placebo in achieving clearance of CMV viremia by week 3 in lung transplant recipients with active CMV infection.
Detailed description
Lung transplant recipients are particularly susceptible to CMV infection due to intensive immunosuppressive regimens required to prevent graft rejection. CMV viremia is associated with increased morbidity, including CMV pneumonitis, and may contribute to chronic lung allograft dysfunction (CLAD).Approximately 30-50% of lung transplant recipients develop CMV infection within the first year post-transplant, with higher rates in CMV-seronegative recipients receiving organs from seropositive donors (D+/R-).
Current standard treatment for CMV infection in transplant recipients involves ganciclovir or its oral prodrug, valganciclovir, which inhibit CMV DNA polymerase. While effective, prolonged use is associated with toxicities, including myelosuppression, and the emergence of resistant strains in some cases. Letermovir, a novel antiviral targeting the CMV terminase complex, has shown efficacy in CMV prophylaxis in hematopoietic stem cell transplant recipients, and in kidney transplant recipients. It has now been extensively studied for use in prophylaxis but there are limited data in treatment. It is an attractive drug in transplant recipients because it has an excellent safety profile and requires no dose adjustment for renal dysfunction. However, data on the use of letermovir for treatment (as opposed to prophylaxis) are more limited. A multicenter study of letermovir use for treatment showed reasonable response rates especially in patients with low viral loads. The use of combination therapy for CMV treatment represents an attractive option, as there is extensive experience with other viruses (e.g. HIV , HCV) to show that this strategy leads to improved response rates and lessens the emergence of antiviral resistance. The use of ganciclovir plus letermovir is attractive because they target two different viral enzymes and both have oral options facilitating outpatient treatment. The most recently published international CMV consensus guidelines reports that the use of combination antiviral therapy is a key research need.
The investigators plan to conduct a pilot trial to determine the efficacy of letermovir plus standard of care (SOC) antiviral therapy in clearing CMV infection. The trial will be conducted in compliance with the protocol, Good Clinical Practices (GCP) and the applicable regulatory requirements.
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 |
|---|---|---|
| SOC antiviral plus placebo | Placebo comparator | Drug: Placebo, Drug: Valganciclovir/GanciclovirPatients will receive the standard of care (SOC) antiviral therapy along with a placebo drug. The placebo drug will be administered for three weeks, while the SOC antiviral duration and dosage will be at the discretion of the treating physician. |
| SOC antiviral plus letermovir active drug | Experimental | Drug: Letermovir, Drug: Valganciclovir/GanciclovirPatients will receive the standard of care (SOC) antiviral therapy in combination with letermovir. The letermovir active drug will be administered for three weeks, while the SOC antiviral treatment duration and dosage will be at the discretion of the treating physician. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Recipient of a lung transplant.
- Has confirmed CMV viremia with a viral load ≥ 1000 IU/mL and will receive or has just started SOC antiviral treatment in the past 72h as per the decision of the treating physician.
Key exclusion criteria (8 listed)
- Renal failure with Creatinine clearance <15 mL/min or requiring dialysis
- Severe hepatic impairment (Child-Pugh Class C)
- Participating in another interventional clinical trial
- Combined transplant (e.g heart-lung, lung-liver)
- Known allergy or contraindication to any of the antiviral medications
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 |
|---|---|---|
| LetermovirLetermovir (480mg) will be given orally as a loading dose every 12 hours for the first 24 hours, then one tablet per day for a total treatment duration of 21 days. Letermovir treatment will be started within 72 hours of starting SOC antiviral treatment as per the decision of the treating physician. | Drug | SOC antiviral plus letermovir active drug |
| PlaceboPlacebo will be dosed the same as letermovir: one tablet every 12 hours for the first 24 hours, then one tablet per day for total treatment duration of 21 days. | Drug | SOC antiviral plus placebo |
| Valganciclovir/GanciclovirGanciclovir or its oral prodrug, valganciclovir will be administered as the standard of care antiviral therapy. Its duration will be at the discretion of the treatment physician but is typically given until clearance of viremia. The clinical definition of viral clearance is one negative viral load or two viral loads one week apart that are <200 IU/mL | Drug | SOC antiviral plus letermovir active drug, SOC antiviral plus placebo |
Primary outcome
Proportion of patients achieving clearance of CMV viremia by week 3, as measured by quantitative PCR.
Time frame: From time of enrollment until 3 weeks after enrolment
Viral clearance is described by a plasma CMV viral load < 200 IU/mL, the UHN clinically used threshold
8 secondary outcomes
Proportion of patients achieving an undetectable viral load
Time frame: At week 3 and by month 6 after enrolment
Proportion of patients achieving CMV viral load <137 IU/mL (lower limit of quantification of the assay)
Time frame: At week 3 from enrolment and at 6 months
Time to clearance of CMV viremia
Time frame: From enrolment until clearance of CMV viremia, up to 6 months after enrolment
Time to resolution of symptoms if present
Time frame: From enrolment until clearance of symptoms, up to 6 months after enrolment
Development of antiviral resistance
Time frame: From enrolment until up to 6 months after enrolment
Incidence of adverse events
Time frame: From enrolment until up to 6 months after enrolment
Proportion of patients with clinically significant CMV recurrence within 6months, as determined by quantitative PCR or symptomatic CMV disease
Time frame: From enrollment until 6 months.
Monthly enrollment rate as a measure of recruitment feasibility
Time frame: From start of enrollment until up to 6 months after the final patient is enrolled
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 17 Feb 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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Letermovir and Valganciclovir/Ganciclovir in people with CMV and Lung Transplant Recipient, run by University Health Network, Toronto at 1 site in Canada.
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 2 inclusion and 8 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 17 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. 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. Some participants in this study may receive a placebo. 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 Atul Humar, MD, FRCPC (416-340-4241, atul.humar@uhn.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of patients achieving clearance of CMV viremia by week 3, as measured by quantitative PCR. (time frame: From time of enrollment until 3 weeks after enrolment). 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 17 Feb 2026.