Cytomegalovirus InfectionsPhase 2NCT06066957
Open Label Trial of Oral Letermovir for CMV Prophylaxis in Thoracic Transplant Recipients
A Phase 2 study testing Letermovir 480 MG [Prevymis] in people with Cytomegalovirus Infections and Transplant-Related Disorder, run by University of Pennsylvania at 1 site in United States.
Trial summary
Open label study to determine tolerability and efficacy of letermovir for CMV prophylaxis in heart and lung transplant recipients. The study hypotheses are: 1. Letermovir prophylaxis will be associated with similar rates of CMV infection as valganciclovir among heart and lung transplant recipients 2. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cytomegalovirus Infections, Transplant-Related Disorder
- What is being tested?
- Letermovir 480 MG [Prevymis]
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Apr 2024to 31 Jan 2027
- Phase
- Phase 2
- 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
- In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- Age is >=18 years on the day of transplantation.
- Heart or Lung transplant recipient.
- Donor and/or Recipient CMV seropositive (defined by positive IgG) within 1 year prior to transplantation.
- Able to start oral CMV prophylaxis within 14 days (heart graft recipients) or 28 days (lung graft recipients) of transplantation.
- Males at birth agree to use contraception during the treatment period, and for at least 90 days after the last dose of study treatment, and refrain from donating sperm during this period.
- Female at birth is not pregnant or breastfeeding. If of childbearing potential, agrees to follow the contraception guidance during the treatment period and for at least 90 days after the last dose of study treatment.
- A male or female subject who is of reproductive potential agrees to true abstinence or to use (or have their partner use) 1 acceptable method of birth control starting from the time of consent through 90 days after the last dose of study therapy. True abstinence is defined as abstinence in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., abstinence only on certain calendar days, abstinence only during ovulation period, use of symptothermal method, use of post-ovulation methods) and withdrawal are not acceptable methods of contraception. Acceptable methods of birth control are: intrauterine device (IUD), diaphragm with spermicide, contraceptive sponge, condom, and vasectomy OR use of appropriate double barrier contraception as per local regulations or guidelines. Hormonal contraceptives (e.g., birth control pills, transdermal patch, or injectables) are unacceptable methods of birth control for use in this study because it is not known whether these methods are affected by co- administration of letermovir.
Who cannot join
- An individual who meets any of the following criteria will be excluded from participation in this study:
- Any prior solid organ transplant.
- Dual organ transplantation.
- Prior treated CMV infection.
- Unknown CMV serostatus of the donor or recipient.
- Suspected or known hypersensitivity to active or inactive ingredients of letermovir formulations and/or acyclovir formulations.
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- CrCl <10 mL/minute, using Cockcroft-Gault equation, or renal replacement therapy at the time of enrollment.
- Child-Pugh Class C severe hepatic insufficiency at enrollment.
- Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 5 x the upper limit of normal (ULN) or serum total bilirubin > 2.5 x ULN. Note: Subjects who meet this exclusion criterion may, at the discretion of the investigator, have one repeat set of relevant labs done. If the repeat value does not meet this criterion, they may continue in the enrollment process.
- Both moderate hepatic insufficiency AND moderate renal insufficiency. Note: Moderate hepatic insufficiency is defined as Child Pugh Class B; moderate renal insufficiency is defined as a creatinine clearance less than 50 mL/min, as calculated by the Cockcroft-Gault equation.
- Neutropenia, defined as absolute neutrophil count <1,500/microliter, at the time of enrollment.
- Severe thrombocytopenia, defined as platelets <50,000/microliter, at the time of enrollment.
- Any uncontrolled infection on the day of enrollment.
- Documented positive results for human immunodeficiency virus antibody (HIV-Ab) test at any time prior to enrollment, or hepatitis B surface antigen (HBsAg) within 90 days prior to enrollment.
- Documented positive result for hepatitis C virus antibody (HCV-Ab) and with detectable HCV ribonucleic acid (RNA) within 90 days prior to enrollment with need for treatment with direct acting antiviral other than the following: glecaprevir/pibrentasvir, sofosbuvir/velpatasvir, or elbasvir/grazoprevir.
- Pregnant or expecting to conceive, is breastfeeding, or plans to breastfeed from the time of consent through at least 90 days following cessation of study therapy.
- Expecting to donate eggs or sperm starting from the time of consent through at least 90 days following cessation of study therapy.
- Received within 30 days prior to enrollment or plans to receive during the study any of the following anti-CMV IgG antibody treatment or anti-CMV drug therapy including the following: Cidofovir, CMV hyper-immune globulin, any investigational CMV antiviral agent/biologic therapy.
- Heart transplant recipients received >14 days of IV ganciclovir or oral valganciclovir prior to initiation of study drug or plans to receive during the study any of the following anti-CMV drug therapy: ganciclovir, valganciclovir, foscarnet. Lung transplant recipients received >28 days of IV ganciclovir or oral valganciclovir prior to initiation of study drug or plans to receive during the study any of the following anti-CMV drug therapy: ganciclovir, valganciclovir, foscarnet.
- Currently participating or has participated in a study with an unapproved investigational compound within 28 days, or 5× half-life of the investigational compound whichever is longer, of initial dosing on this study.
- Previously participated in this study or any other study involving letermovir.
- Previously participated or is currently participating in any study involving administration of a CMV vaccine or another CMV investigational agent or is planning to participate in a study of a CMV vaccine or another CMV investigational agent during the course of this study.
- For unexposed subjects, any letermovir exposure.
- Are unable to take medications orally by day 14 post heart transplant or by day 28 post lung transplant.
Trial locations and contacts
1 site in 1 country.
United States1 site
Penn Medicine at the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
Official title: Open Label Trial of Tolerability and Efficacy of Oral Letermovir for CMV Prophylaxis Among Heart and Lung Transplant Recipients
Open label study to determine tolerability and efficacy of letermovir for CMV prophylaxis in heart and lung transplant recipients. The study hypotheses are:
- Letermovir prophylaxis will be associated with similar rates of CMV infection as valganciclovir among heart and lung transplant recipients
- Letermovir will be better tolerated than valganciclovir for CMV prophylaxis in heart and lung transplant recipients, with a higher proportion of days of completed therapy with correct dosing during the planned prophylaxis period
- Letermovir will have a lower rate of neutropenia than valganciclovir when used for CMV prophylaxis in heart and lung transplant recipients
- Incorrect renal dosing will occur less frequently with letermovir than with valganciclovir when used for CMV prophylaxis in heart and lung transplant recipients
Read the detailed description
This study is a prospective cohort design. Subjects exposed to letermovir for CMV prophylaxis following heart or lung transplantation will be compared with those who received standard valganciclovir prophylaxis in the two years before the study began (referred to as the "pre-intervention" period). The goal is to evaluate the efficacy and tolerability of letermovir.
- Being tested
- Letermovir 480 MG [Prevymis]
- Keywords
- CMV, Thoracic Transplant
- Medical subject headings
- Cytomegalovirus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Letermovir 480 MG [Prevymis]Drug
Letermovir for CMV prophylaxis in thoracic organ transplant recipients.
Letermovir will be administered by oral administration, as per study protocol. The intended duration of therapy will be up to 365 days, depending on organ transplanted and donor and recipient CMV status. However, treatment may discontinued as discussed in Section 7.
Letermovir is dosed at 480mg daily for patients with CrCl >10. Dose adjustment, as per package insert, is recommended in setting of co-administration of cyclosporine, with dose reduction of letermovir to 240mg daily. Missed doses of letermovir will not be made up.
| Study group | Role | What they receive |
|---|---|---|
| Letermovir | Experimental | Will include those participants who receive letermovir for CMV prophylaxis as provided through the clinical trial. The "exposed" group will be ascertained prospectively over a one-year period (the "post-intervention" period). Receives: Drug: Letermovir 480 MG [Prevymis] |
What is being measured
The primary outcome is the main question the study is designed to answer.
CMV viral load
The primary outcome will be CMV infection (CMV viremia with CMV viral load >1,000, CMV syndrome, or tissue invasive CMV disease) during the planned prophylaxis period and the following 180 days
Measured: Prophylaxis period plus 180 days
Proportion of days during which appropriately renally-dosed prophylaxis
The primary outcome will be the proportion of days during which appropriately-dosed prophylaxis was received during the planned treatment course.
Measured: 90 to 365 days post intervention
Secondary outcomes (6)
Biopsy-proven acute cellular rejection
The proportion of subjects who develop biopsy-proven acute cellular rejection
Measured: Prophylaxis period plus 180 days
Proportion of subjects who develop CMV resistance
CMV resistance will be determined by the presence of a clinically significant mutation on genomic sequencing
Measured: Prophylaxis period plus 180 days
Proportion of subjects who develop neutropenia
Proportion of subjects who develop Neutropenia (absolute neutrophil count (ANC) less than 1,500/microliter)
Measured: 90 to 365 days of prophylaxis period
Proportion of subjects who develop severe thrombocytopenia (platelet count less than 50,000/microliter)
Proportion of subjects who develop severe thrombocytopenia (platelet count less than 50,000/microliter)
Measured: 90 to 365 days of prophylaxis period
Proportion of subjects with Unplanned discontinuation of MMF or azathioprine
Proportion of subjects with Unplanned discontinuation of MMF or azathioprine
Measured: 90 to 365 days of prophylaxis period
Number subjects with Incorrect renal dosing at any point during the planned prophylaxis period (measured as a binary variable, where the outcome is met if the recipient receives any days of incorrect dosing per their GFR).
Number subjects with Incorrect renal dosing at any point during the planned prophylaxis period (measured as a binary variable, where the outcome is met if the recipient receives any days of incorrect dosing per their GFR).
Measured: 90 to 365 days of prophylaxis period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Oct 2023
- Study start4 Apr 2024
- Primary completion15 Dec 2026 (estimated)
- Study completion31 Jan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cytomegalovirus InfectionsStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This study is a prospective cohort design. Subjects exposed to letermovir for CMV prophylaxis following heart or lung transplantation will be compared with those who received standard valganciclovir prophylaxis in the two years before the study began (referred to as the "pre-intervention" period). The goal is to evaluate the efficacy and tolerability of letermovir.
- Masking
- None (open label)
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06066957
- Sponsor's protocol ID
- 853851
- Status last verified
- Sep 2026
- First submitted
- 13 Sep 2023
- Last updated
- 24 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 24 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open Label Trial of Tolerability and Efficacy of Oral Letermovir for CMV Prophylaxis Among Heart and Lung Transplant Recipients
- ClinicalTrials.gov ID
- NCT06066957
- Acronym / sponsor ID
- 853851
- Keywords
- CMV, Thoracic Transplant
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 4 Apr 2024 (actual)
- Primary completion
- 15 Dec 2026 (estimated)
- Study completion
- 31 Jan 2027 (estimated)
- First posted
- 4 Oct 2023 (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.
Open label study to determine tolerability and efficacy of letermovir for CMV prophylaxis in heart and lung transplant recipients. The study hypotheses are:
- Letermovir prophylaxis will be associated with similar rates of CMV infection as valganciclovir among heart and lung transplant recipients
- Letermovir will be better tolerated than valganciclovir for CMV prophylaxis in heart and lung transplant recipients, with a higher proportion of days of completed therapy with correct dosing during the planned prophylaxis period
- Letermovir will have a lower rate of neutropenia than valganciclovir when used for CMV prophylaxis in heart and lung transplant recipients
- Incorrect renal dosing will occur less frequently with letermovir than with valganciclovir when used for CMV prophylaxis in heart and lung transplant recipients
Detailed description
This study is a prospective cohort design. Subjects exposed to letermovir for CMV prophylaxis following heart or lung transplantation will be compared with those who received standard valganciclovir prophylaxis in the two years before the study began (referred to as the "pre-intervention" period). The goal is to evaluate the efficacy and tolerability of letermovir.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This study is a prospective cohort design. Subjects exposed to letermovir for CMV prophylaxis following heart or lung transplantation will be compared with those who received standard valganciclovir prophylaxis in the two years before the study began (referred to as the "pre-intervention" period). The goal is to evaluate the efficacy and tolerability of letermovir.
| Arm | Type | Receives |
|---|---|---|
| Letermovir | Experimental | Drug: Letermovir 480 MG [Prevymis]Will include those participants who receive letermovir for CMV prophylaxis as provided through the clinical trial. The "exposed" group will be ascertained prospectively over a one-year period (the "post-intervention" period). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- Age is >=18 years on the day of transplantation.
- Heart or Lung transplant recipient.
- Donor and/or Recipient CMV seropositive (defined by positive IgG) within 1 year prior to transplantation.
- Able to start oral CMV prophylaxis within 14 days (heart graft recipients) or 28 days (lung graft recipients) of transplantation.
Key exclusion criteria (24 listed)
- An individual who meets any of the following criteria will be excluded from participation in this study:
- Any prior solid organ transplant.
- Dual organ transplantation.
- Prior treated CMV infection.
- Unknown CMV serostatus of the donor or recipient.
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 |
|---|---|---|
| Letermovir 480 MG [Prevymis]Letermovir for CMV prophylaxis in thoracic organ transplant recipients. Letermovir will be administered by oral administration, as per study protocol. The intended duration of therapy will be up to 365 days, depending on organ transplanted and donor and recipient CMV status. However, treatment may discontinued as discussed in Section 7. Letermovir is dosed at 480mg daily for patients with CrCl >10. Dose adjustment, as per package insert, is recommended in setting of co-administration of cyclosporine, with dose reduction of letermovir to 240mg daily. Missed doses of letermovir will not be made up. | Drug | Letermovir |
Primary outcome
CMV viral load
Time frame: Prophylaxis period plus 180 days
The primary outcome will be CMV infection (CMV viremia with CMV viral load >1,000, CMV syndrome, or tissue invasive CMV disease) during the planned prophylaxis period and the following 180 days
Proportion of days during which appropriately renally-dosed prophylaxis
Time frame: 90 to 365 days post intervention
The primary outcome will be the proportion of days during which appropriately-dosed prophylaxis was received during the planned treatment course.
6 secondary outcomes
Biopsy-proven acute cellular rejection
Time frame: Prophylaxis period plus 180 days
Proportion of subjects who develop CMV resistance
Time frame: Prophylaxis period plus 180 days
Proportion of subjects who develop neutropenia
Time frame: 90 to 365 days of prophylaxis period
Proportion of subjects who develop severe thrombocytopenia (platelet count less than 50,000/microliter)
Time frame: 90 to 365 days of prophylaxis period
Proportion of subjects with Unplanned discontinuation of MMF or azathioprine
Time frame: 90 to 365 days of prophylaxis period
Number subjects with Incorrect renal dosing at any point during the planned prophylaxis period (measured as a binary variable, where the outcome is met if the recipient receives any days of incorrect dosing per their GFR).
Time frame: 90 to 365 days of prophylaxis period
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 24 Sep 2026.
- Individual participant dataSharing planned: Undecided
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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. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Letermovir 480 MG [Prevymis] in people with Cytomegalovirus Infections and Transplant-Related Disorder, run by University of Pennsylvania at 1 site in United States.
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 8 inclusion and 24 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: under way, not looking for participants, as of the sponsor's last update on 24 Sep 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 United States. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
CMV viral load (time frame: Prophylaxis period plus 180 days). The study lists 2 primary outcomes in all. 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 24 Sep 2026.