Cytomegalovirus InfectionPhase 3NCT03930615
Extension of Letermovir (LET) From Day 100 to Day 200 Post-transplant for the Prevention of Cytomegalovirus (CMV) Infection in Hematopoietic Stem Cell Transplant (HSCT) Participants (MK-8228-040)
A Phase 3 study testing Letermovir in people with Cytomegalovirus Infection, run by Merck Sharp & Dohme LLC at 32 sites in 6 countries.
Trial summary
The purpose of this study was to evaluate the safety and efficacy of letermovir (LET) versus placebo when cytomegalovirus (CMV) prophylaxis was extended from 100 days to 200 days post-transplant in CMV seropositive participants who received an allogenic hematopoietic stem cell transplant (HSCT). 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
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 220 participants
- Where
- 32 sitesin 6 countries
- Study dates
- 21 Jun 2019to 16 Mar 2022
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- have documented positive CMV serostatus (CMV immunoglobulin G [IgG] seropositive) for recipient (R+) at the time of transplant
- has a history of allogeneic HSCT (bone marrow, peripheral blood stem cell, or cord blood transplant) within ~100 days prior to randomization
- has undetectable CMV deoxyribonucleic acid (DNA) or detectable/not quantifiable CMV DNA from a plasma sample collected within 14 days prior to randomization
- has received LET as primary prophylaxis that started within 28 days of HSCT and continued through Week 14 post-transplant (± 1 week) prior to randomization
- is at high risk of CMV disease, defined as meeting one or more of the following criteria:
- has a related donor with at least 1 mismatch at 1 of the specified 3 human leukocyte antigen (HLA) gene loci (HLA-A, B, or DR)
Show all 14Show fewer
- has an unrelated donor with at least one mismatch at one of the specified four HLA gene loci (HLA-A, B, C, and DRB1)
- has a haploidentical donor
- has umbilical cord blood as the stem-cell source
- has ex-vivo T-cell-depleted grafts
- has received anti-thymocyte globulin
- has received alemtuzumab
- has graft versus host disease (GVHD) or other conditions, requiring the use of systemic prednisone (or equivalent) at a dose of ≥1 mg/kg of body weight per day within 6 weeks of randomization
- for female participants, is not pregnant or breastfeeding, and is either not a woman of childbearing potential (WOCBP) or is a WOBCP who agrees to use acceptable contraception during the treatment period and for ≥28 days after the last dose of study drug.
Who cannot join
- has a history of CMV end-organ disease or preemptive treatment therapy for CMV after HSCT prior to randomization
- has a history of >14 days total of LET interruption during the first 100 days post-transplant prior to randomization
- has suspected or known hypersensitivity to active or inactive ingredients of LET formulations
- has severe hepatic insufficiency defined as Child-Pugh Class C within 14 days prior to randomization.
- has serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >5× the upper limit of normal (ULN) within 14 days prior to randomization
- has end-stage renal impairment with a creatinine clearance less than 10 mL/min, as calculated by the Cockcroft-Gault equation using serum creatinine within 14 days prior to randomization
Show all 18Show fewer
- has both moderate hepatic insufficiency AND moderate-to-severe renal insufficiency
- has an uncontrolled infection on the day of enrollment
- requires mechanical ventilation or is hemodynamically unstable at the time of enrollment
- has a documented positive result for a human immunodeficiency virus antibody (HIV-Ab) test at any time prior to screening, or for hepatitis C virus antibody (HCV-Ab) with detectable HCV ribonucleic acid (RNA), or hepatitis B surface antigen (HBsAg) within 6 months prior to screening.
- has active solid tumor malignancies with the exception of localized basal cell or squamous cell skin cancer or the condition under treatment (eg, lymphomas)
- has received cidofovir or CMV immunoglobulin with 30 days prior to screening
- is currently participating or has participated in a study with an unapproved investigational compound, monoclonal antibody, or device within 28 days or 5× half-life of the investigational compound or monoclonal antibody, whichever is longer, of initial dosing in this study
- has previously participated in this study or any other study involving LET, 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
- is pregnant or expecting to conceive, is breastfeeding, or plans to breastfeed from the time of consent through 28 days after the last dose of study therapy
- is expecting to donate eggs starting from the time of consent through 28 days after the last dose of study therapy
- has clinically relevant drug or alcohol abuse within 12 months of screening that may interfere with participant treatment, assessment, or compliance with the protocol as assessed by the investigator
- has a history or current evidence of any condition, therapy, lab abnormality, or other circumstance that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or would be put at undue risk as judged by the investigator, such that it is not in the best interest of the participant to participate in this study
Trial locations and contacts
32 sites in 6 countries.
32 sites in 6 countries
United States10 sites
Brigham & Women's Hospital ( Site 0161)
Boston, Massachusetts, 02115
City of Hope National Medical Center ( Site 0158)
Duarte, California, 91010
Duke University Medical Center ( Site 0169)
Durham, North Carolina, 27710
John Theurer Cancer Center at Hackensack University Med Ctr ( Site 0174)
Hackensack, New Jersey, 07601
The University of Texas MD Anderson Cancer Center ( Site 0154)
Houston, Texas, 77030
Indiana Blood and Marrow Transplantation ( Site 0175)
Indianapolis, Indiana, 46237
University of Miami, Sylvester Comprehensive Cancer Center ( Site 0160)
Miami, Florida, 33136
Memorial Sloan Kettering Cancer Center ( Site 0164)
New York, New York, 10065
University of California Davis Medical Center ( Site 0156)
Sacramento, California, 95817
Fred Hutchinson Cancer Research Center ( Site 0152)
Seattle, Washington, 98109
France6 sites
CHU Henri Mondor ( Site 0032)
Créteil, Val-de-Marne, 94110
Centre Hospitalier Universitaire Dupuytren ( Site 0182)
Limoges, Haute-Vienne, 87042
Hopital Saint Eloi ( Site 0031)
Montpellier, Herault, 34295
CHU Hopital Saint Antoine ( Site 0036)
Paris, 75012
Centre Hopitalier Lyon Sud ( Site 0039)
Pierre-Bénite, Rhone, 69495
Institut Gustave Roussy ( Site 0038)
Villejuif, Val-de-Marne, 94805
Italy5 sites
ASST Spedali Civili di Brescia ( Site 0052)
Brescia, Lombardy, 25123
IRCCS Ospedale San Raffaele ( Site 0051)
Milan, 20132
Fondazione PTV Policlinico Tor Vergata ( Site 0054)
Roma, 00133
Policlinico Umberto I ( Site 0056)
Roma, 00161
Policlinico Universitario Agostino Gemelli ( Site 0055)
Roma, 00168
United Kingdom5 sites
Queen Elizabeth University Hospital [Glasgow, UK] ( Site 0096)
Glasgow, Glasgow City, G51 4TF
1Kings College Hospital ( Site 0091)
London, London, City of, SE5 9RS
UCL Cancer Institute ( Site 0093)
London, London, City of, WC1E 6BT
Manchester Royal Infirmary ( Site 0097)
Manchester, M13 9WL
Freeman Hospital Newcastle upon Tyne Foundation NHS Trust ( Site 0092)
Newcastle upon Tyne, NE7 7DN
Germany3 sites
Universitaetsklinik Koeln ( Site 0041)
Cologne, North Rhine-Westphalia, 50937
Universitaetsklinikum Heidelberg-Medizinische Klinik V ( Site 0042)
Heidelberg, Baden-Wurttemberg, 69120
Universitaetsklinikum Muenster ( Site 0043)
Münster, North Rhine-Westphalia, 48149
Japan3 sites
Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital ( Site 0121)
Hiroshima, 730-8619
National Hospital Organization Kumamoto Medical Center ( Site 0122)
Kumamoto, 860-0008
Jichi Medical University Hospital ( Site 0123)
Shimotsuke, Tochigi, 329-0498
About this study
Official title: A Phase 3 Randomized, Double-blind, Placebo-controlled Clinical Trial to Evaluate the Safety and Efficacy of Letermovir (LET) Prophylaxis When Extended From 100 Days to 200 Days Post-transplant in Cytomegalovirus (CMV) Seropositive Recipients (R+) of an Allogenic Hematopoietic Stem Cell Transplant (HSCT)
The purpose of this study was to evaluate the safety and efficacy of letermovir (LET) versus placebo when cytomegalovirus (CMV) prophylaxis was extended from 100 days to 200 days post-transplant in CMV seropositive participants who received an allogenic hematopoietic stem cell transplant (HSCT). It was hypothesized that LET is superior to placebo in the prevention of clinically-significant CMV infection when LET prophylaxis is extended from 100 to 200 days.
- Conditions
- Cytomegalovirus Infection
- Being tested
- Letermovir, Placebo
- 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
Also called PREVYMIS™, MK-8228
LET tablet or intravenous infusion at a total daily dose of 240 mg (when given with cyclosporin A) or 480 mg (when given alone).
PlaceboDrug
Placebo was administered as tablets matched to LET or as inactive (saline or dextrose) intravenous infusion.
| Study group | Role | What they receive |
|---|---|---|
| Letermovir | Experimental | Participants who received HSCT transplant and 100 days of LET prophylaxis were randomized to an additional 100 days of LET (480 mg once daily alone or 240 mg once daily for participants on cyclosporin A) treatment. Receives: Drug: Letermovir |
| Placebo | Placebo comparator | Participants who received HSCT transplant and 100 days of LET prophylaxis were randomized to an additional 100 days of placebo treatment. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Clinically Significant CMV Infection From Week 14 (~100 Days) Post-transplant Through Week 28 (~200 Days) Post-transplant
Clinically significant CMV infection is either the onset of probable or proven CMV end-organ disease or initiation of anti-CMV preemptive therapy (PET) with approved anti-CMV agents (ganciclovir, valganciclovir, foscarnet, and/or cidofovir) based on documented CMV viremia and the clinical condition of the participant. Missing values were handled by the observed failure (OF) approach where failure was defined as all participants who develop clinically significant CMV infection or discontinue prematurely from the study with CMV viremia from week 14 (~100 days) through week 28 post-transplant. It was hypothesized that LET is superior to placebo in the prevention of clinically significant CMV infection when LET prophylaxis is extended from 100 to 200 days.
Measured: From Week 14 post-transplant to Week 28 post-transplant (approximately 14 weeks)
Secondary outcomes (12)
Percentage of Participants Experiencing ≥1 Adverse Events (AEs) From Week 14 (~100 Days) Post-transplant Through Week 28 (~200 Days) Post-transplant
An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Measured: From Week 14 post-transplant to Week 28 post-transplant (approximately 14 weeks)
Percentage of Participants Withdrawing From Study Drug Due to an AE From Week 14 (~100 Days) Post-transplant Through Week 28 (~200 Days) Post-transplant
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Measured: From Week 14 post-transplant to Week 28 post-transplant (approximately 14 weeks)
Percentage of Participants With Clinically Significant CMV Infection From Week 14 Post-transplant Through Week 38 Post-transplant
Clinically significant CMV infection is either the onset of probable or proven CMV end-organ disease or initiation of anti-CMV PET with approved anti-CMV agents (ganciclovir, valganciclovir, foscarnet, and/or cidofovir) based on documented CMV viremia and the clinical condition of the participant. Missing values were handled by the OF approach where failure was defined as all participants who develop clinically significant CMV infection or discontinue prematurely from the study with CMV viremia from week 14 (~100 days) through week 38 post-transplant.
Measured: From Week 14 post-transplant to Week 38 post-transplant (approximately 24 weeks)
Percentage of Participants With Clinically Significant CMV Infection From Week 14 Post-transplant Through Week 48 Post-transplant
Clinically significant CMV infection is either the onset of probable or proven CMV end-organ disease or initiation of anti-CMV PET with approved anti-CMV agents (ganciclovir, valganciclovir, foscarnet, and/or cidofovir) based on documented CMV viremia and the clinical condition of the participant. Missing values were handled by the OF approach where failure was defined as all participants who develop clinically significant CMV infection or discontinue prematurely from the study with CMV viremia from week 14 (~100 days) through week 48 post-transplant.
Measured: From Week 14 post-transplant to Week 48 post-transplant (approximately 34 weeks)
Time to Onset of Clinically Significant CMV Infection From Week 14 Post-transplant to Week 28 Post-transplant
Clinically significant CMV infection is either the onset of probable or proven CMV end-organ disease or initiation of anti-CMV PET with approved anti-CMV agents (ganciclovir, valganciclovir, foscarnet, and/or cidofovir) based on documented CMV viremia and the clinical condition of the participant. Time to onset of clinically significant CMV infection is the elapsed time from transplant to the onset of CMV end-organ disease or to the initiation of anti-CMV PET. Time to onset was determined from the Kaplan-Meier method for censored data.
Measured: From Week 14 post-transplant to Week 28 post-transplant (approximately 14 weeks)
Time to Onset of Clinically Significant CMV Infection From Week 14 Post-transplant to Week 48 Post-transplant
Clinically significant CMV infection is either the onset of probable or proven CMV end-organ disease or initiation of anti-CMV PET with approved anti-CMV agents (ganciclovir, valganciclovir, foscarnet, and/or cidofovir) based on documented CMV viremia and the clinical condition of the participant. Time to onset of clinically significant CMV infection is the elapsed time from transplant to the onset of CMV end-organ disease or to the initiation of anti-CMV PET. Time to onset was determined from the Kaplan-Meier method for censored data.
Measured: From Week 14 post-transplant to Week 48 post-transplant (approximately 34 weeks)
Percentage of Participants With CMV Viremia Who Started PET From Week 14 Post-transplant to Week 28 Post-transplant
The percentage of participants with CMV viremia who initiated PET of anti-CMV agents (ganciclovir, valganciclovir, foscarnet, and/or cidofovir) was determined. Missing values were handled with the OF approach, where failure was defined as all participants who develop clinically significant CMV infection or discontinue prematurely from the study with CMV viremia from week 14 through week 28 post-transplant.
Measured: From Week 14 post-transplant to Week 28 post-transplant (approximately 14 weeks)
Percentage of Participants With CMV Viremia Who Started PET From Week 14 Post-transplant to Week 48 Post-transplant
The percentage of participants with CMV viremia who initiated PET of anti-CMV agents (ganciclovir, valganciclovir, foscarnet, and/or cidofovir) was determined. Missing values were handled with the OF approach, where failure was defined as all participants who develop clinically significant CMV infection or discontinue prematurely from the study with CMV viremia from week 14 through week 48 post-transplant.
Measured: From Week 14 post-transplant to Week 48 post-transplant (approximately 34 weeks)
Percentage of Participants With All-cause Mortality From Week 14 Post-transplant to Week 28 Post-transplant
The percentage of participants who died due to any cause (all-cause mortality) from Week 14 to Week 28 was determined.
Measured: From Week 14 post-transplant to Week 28 post-transplant (approximately 14 weeks)
Percentage of Participants With All-cause Mortality From Week 14 Post-transplant to Week 48 Post-transplant
The percentage of participants who died due to any cause (all-cause mortality) from Week 14 to Week 48 was determined.
Measured: From Week 14 post-transplant to Week 48 post-transplant (approximately 34 weeks)
Time to All-cause Mortality From Week 14 Post-transplant to Week 28 Post-transplant
Time to all-cause mortality is the time elapsed after Week 14 post-transplant and death due to any cause, and was determined from the Kaplan-Meier method for censored data.
Measured: From Week 14 post-transplant to Week 28 post-transplant (approximately 14 weeks)
Time to All-cause Mortality From Week 14 Post-transplant to Week 48 Post-transplant
Time to all-cause mortality is the time elapsed after Week 14 post-transplant and death due to any cause, and was determined from the Kaplan-Meier method for censored data.
Measured: From Week 14 post-transplant to Week 48 post-transplant (approximately 34 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Apr 2019
- Study start21 Jun 2019
- Primary completion27 Oct 2021
- Study completion16 Mar 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Cytomegalovirus InfectionStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 220 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03930615
- Sponsor's protocol ID
- 8228-040
- Other IDs
- MK-8228-040, 194797, 2018-001038-17, 2018
- Status last verified
- Jul 2024
- First submitted
- 26 Apr 2019
- Last updated
- 22 Aug 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Publications
Russo D, Schmitt M, Pilorge S, Stelljes M, Kawakita T, Teal VL, Haber B, Bopp C, Dadwal SS, Badshah C. Efficacy and safety of extended duration letermovir prophylaxis in recipients of haematopoietic stem-cell transplantation at risk of cytomegalovirus infection: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Haematol. 2024 Feb;11(2):e127-e135. doi: 10.1016/S2352-3026(23)00344-7. Epub 2023 Dec 21.
PubMed 38142695Dwabe S, Hsiao M, Ali A, Rodman J, Savitala-Damerla L, Nazaretyan S, Kimberly Schiff NP, Tam E, Ladha A, Woan K, Chaudhary P, Yaghmour G. Real world experience: Examining outcomes using letermovir for CMV prophylaxis in high-risk allogeneic hematopoietic stem cell patients in the setting of using T-cell depletion as GVHD prophylaxis. Transpl Immunol. 2023 Feb;76:101769. doi: 10.1016/j.trim.2022.101769. Epub 2022 Dec 2.
PubMed 36464218
Study at a glance
From the registry record, last updated by the sponsor on 22 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3 Randomized, Double-blind, Placebo-controlled Clinical Trial to Evaluate the Safety and Efficacy of Letermovir (LET) Prophylaxis When Extended From 100 Days to 200 Days Post-transplant in Cytomegalovirus (CMV) Seropositive Recipients (R+) of an Allogenic Hematopoietic Stem Cell Transplant (HSCT)
- ClinicalTrials.gov ID
- NCT03930615
- Acronym / sponsor ID
- 8228-040
- Conditions
- Cytomegalovirus Infection
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 220 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 21 Jun 2019 (actual)
- Primary completion
- 27 Oct 2021 (actual)
- Study completion
- 16 Mar 2022 (actual)
- First posted
- 29 Apr 2019 (actual)
- Results
- Posted 1 Nov 2022
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 was to evaluate the safety and efficacy of letermovir (LET) versus placebo when cytomegalovirus (CMV) prophylaxis was extended from 100 days to 200 days post-transplant in CMV seropositive participants who received an allogenic hematopoietic stem cell transplant (HSCT). It was hypothesized that LET is superior to placebo in the prevention of clinically-significant CMV infection when LET prophylaxis is extended from 100 to 200 days.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Letermovir | Experimental | Drug: LetermovirParticipants who received HSCT transplant and 100 days of LET prophylaxis were randomized to an additional 100 days of LET (480 mg once daily alone or 240 mg once daily for participants on cyclosporin A) treatment. |
| Placebo | Placebo comparator | Drug: PlaceboParticipants who received HSCT transplant and 100 days of LET prophylaxis were randomized to an additional 100 days of placebo treatment. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- have documented positive CMV serostatus (CMV immunoglobulin G [IgG] seropositive) for recipient (R+) at the time of transplant
- has a history of allogeneic HSCT (bone marrow, peripheral blood stem cell, or cord blood transplant) within ~100 days prior to randomization
- has undetectable CMV deoxyribonucleic acid (DNA) or detectable/not quantifiable CMV DNA from a plasma sample collected within 14 days prior to randomization
- has received LET as primary prophylaxis that started within 28 days of HSCT and continued through Week 14 post-transplant (± 1 week) prior to randomization
- is at high risk of CMV disease, defined as meeting one or more of the following criteria:
Key exclusion criteria (18 listed)
- has a history of CMV end-organ disease or preemptive treatment therapy for CMV after HSCT prior to randomization
- has a history of >14 days total of LET interruption during the first 100 days post-transplant prior to randomization
- has suspected or known hypersensitivity to active or inactive ingredients of LET formulations
- has severe hepatic insufficiency defined as Child-Pugh Class C within 14 days prior to randomization.
- has serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >5× the upper limit of normal (ULN) within 14 days prior to randomization
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 |
|---|---|---|
| LetermovirAlso: PREVYMIS™, MK-8228LET tablet or intravenous infusion at a total daily dose of 240 mg (when given with cyclosporin A) or 480 mg (when given alone). | Drug | Letermovir |
| PlaceboPlacebo was administered as tablets matched to LET or as inactive (saline or dextrose) intravenous infusion. | Drug | Placebo |
Primary outcome
Percentage of Participants With Clinically Significant CMV Infection From Week 14 (~100 Days) Post-transplant Through Week 28 (~200 Days) Post-transplant
Time frame: From Week 14 post-transplant to Week 28 post-transplant (approximately 14 weeks)
Clinically significant CMV infection is either the onset of probable or proven CMV end-organ disease or initiation of anti-CMV preemptive therapy (PET) with approved anti-CMV agents (ganciclovir, valganciclovir, foscarnet, and/or cidofovir) based on documented CMV viremia and the clinical condition of the participant. Missing values were handled by the observed failure (OF) approach where failure was defined as all participants who develop clinically significant CMV infection or discontinue prematurely from the study with CMV viremia from week 14 (~100 days) through week 28 post-transplant. It was hypothesized that LET is superior to placebo in the prevention of clinically significant CMV infection when LET prophylaxis is extended from 100 to 200 days.
12 secondary outcomes
Percentage of Participants Experiencing ≥1 Adverse Events (AEs) From Week 14 (~100 Days) Post-transplant Through Week 28 (~200 Days) Post-transplant
Time frame: From Week 14 post-transplant to Week 28 post-transplant (approximately 14 weeks)
Percentage of Participants Withdrawing From Study Drug Due to an AE From Week 14 (~100 Days) Post-transplant Through Week 28 (~200 Days) Post-transplant
Time frame: From Week 14 post-transplant to Week 28 post-transplant (approximately 14 weeks)
Percentage of Participants With Clinically Significant CMV Infection From Week 14 Post-transplant Through Week 38 Post-transplant
Time frame: From Week 14 post-transplant to Week 38 post-transplant (approximately 24 weeks)
Percentage of Participants With Clinically Significant CMV Infection From Week 14 Post-transplant Through Week 48 Post-transplant
Time frame: From Week 14 post-transplant to Week 48 post-transplant (approximately 34 weeks)
Time to Onset of Clinically Significant CMV Infection From Week 14 Post-transplant to Week 28 Post-transplant
Time frame: From Week 14 post-transplant to Week 28 post-transplant (approximately 14 weeks)
Time to Onset of Clinically Significant CMV Infection From Week 14 Post-transplant to Week 48 Post-transplant
Time frame: From Week 14 post-transplant to Week 48 post-transplant (approximately 34 weeks)
Percentage of Participants With CMV Viremia Who Started PET From Week 14 Post-transplant to Week 28 Post-transplant
Time frame: From Week 14 post-transplant to Week 28 post-transplant (approximately 14 weeks)
Percentage of Participants With CMV Viremia Who Started PET From Week 14 Post-transplant to Week 48 Post-transplant
Time frame: From Week 14 post-transplant to Week 48 post-transplant (approximately 34 weeks)
Percentage of Participants With All-cause Mortality From Week 14 Post-transplant to Week 28 Post-transplant
Time frame: From Week 14 post-transplant to Week 28 post-transplant (approximately 14 weeks)
Percentage of Participants With All-cause Mortality From Week 14 Post-transplant to Week 48 Post-transplant
Time frame: From Week 14 post-transplant to Week 48 post-transplant (approximately 34 weeks)
Time to All-cause Mortality From Week 14 Post-transplant to Week 28 Post-transplant
Time frame: From Week 14 post-transplant to Week 28 post-transplant (approximately 14 weeks)
Time to All-cause Mortality From Week 14 Post-transplant to Week 48 Post-transplant
Time frame: From Week 14 post-transplant to Week 48 post-transplant (approximately 34 weeks)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Aug 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 38142695Russo D, Schmitt M, Pilorge S, Stelljes M, Kawakita T, Teal VL, Haber B, Bopp C, Dadwal SS, Badshah C. Efficacy and safety of extended duration letermovir prophylaxis in recipients of haematopoietic stem-cell transplantation at risk of cytomegalovirus infection: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Haematol. 2024 Feb;11(2):e127-e135. doi: 10.1016/S2352-3026(23)00344-7. Epub 2023 Dec 21.
- Derived from this study: PubMed 36464218Dwabe S, Hsiao M, Ali A, Rodman J, Savitala-Damerla L, Nazaretyan S, Kimberly Schiff NP, Tam E, Ladha A, Woan K, Chaudhary P, Yaghmour G. Real world experience: Examining outcomes using letermovir for CMV prophylaxis in high-risk allogeneic hematopoietic stem cell patients in the setting of using T-cell depletion as GVHD prophylaxis. Transpl Immunol. 2023 Feb;76:101769. doi: 10.1016/j.trim.2022.101769. Epub 2022 Dec 2.
- Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Related trials for Cytomegalovirus Infection
RecruitingObservational study
A Study of LIVTENCITY (Maribavir) in Adults With Cytomegalovirus (CMV) Infection After Transplantation in South Korea
Cytomegalovirus (CMV)
RecruitingObservational study
The Natural History of Severe Viral Infections and Characterization of Immune Defects in Patients Without Known Immunocompromise
EBV, HSV
RecruitingPhase 1
TETRAVI Multivirus CTL for Treatment of EBV, CMV, Adenovirus, and BK Infections Post Allogeneic SCT.
Viral Infection
RecruitingPhase 2
CMV CTLs in Neonates With CMV Infection
Congenital Cytomegaloviral (CMV) Disease
RecruitingPhase 2
CMV-MVA Triplex Vaccination in HLA-Matched Related Stem Cell Donors for the Prevention of CMV Infection in Patients Undergoing Hematopoietic Stem Cell Transplant
Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia
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.
Medical Director study director
Merck Sharp & Dohme LLC
32 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Letermovir in people with Cytomegalovirus Infection, run by Merck Sharp & Dohme LLC at 32 sites in 6 countries.
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 14 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: finished, as of the sponsor's last update on 22 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 32 sites in United States, France, Italy, United Kingdom, Germany and 1 more country. 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 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?
Yes. Results are posted in the registry (first posted 1 Nov 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Percentage of Participants With Clinically Significant CMV Infection From Week 14 (~100 Days) Post-transplant Through Week 28 (~200 Days) Post-transplant (time frame: From Week 14 post-transplant to Week 28 post-transplant (approximately 14 weeks)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03930615, which also lists 2 linked publications.
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 22 Aug 2024.