Phase 3
Completed N=570
Letermovir (MK-8228) Versus Placebo in the Prevention of Clinically-Significant Cytomegalovirus (CMV) Infection in Adult, CMV-Seropositive Allogeneic Hematopoietic Stem Cell Transplant Recipients (MK-8228-001)
Prevention of CMV Infection or Disease
Source: ClinicalTrials.gov NCT02137772 ↗
Enrolled (actual)
570
Serious AEs
56.1%
Results posted
Nov 2017
Primary outcomePrimary: Percentage of Participants With Clinically-significant CMV Infection up to Week 24 Post-transplant — 37.5; 60.6 Percentage of participants — p=<0.0001
◆ Published Evidence
Highly cited
1,207citations · ~134 / year
Letermovir Prophylaxis for Cytomegalovirus in Hematopoietic-Cell Transplantation.
Summary
The study evaluated the efficacy and safety of letermovir (MK-8228) for the prevention of clinically-significant CMV infection in adult, CMV-seropositive recipients of allogeneic hematopoietic stem cell transplant (HSCT). The hypothesis being tested was that MK-8228 is superior to placebo in the prevention of clinically-significant CMV infection through Week 24 post-transplant.
Linked Publications (4)
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Letermovir Prophylaxis for Cytomegalovirus in Hematopoietic-Cell Transplantation.
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A Mortality Analysis of Letermovir Prophylaxis for Cytomegalovirus (CMV) in CMV-seropositive Recipients of Allogeneic Hematopoietic Cell Transplantation.
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Population pharmacokinetics of letermovir following oral and intravenous administration in healthy participants and allogeneic hematopoietic cell transplantation recipients.
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Exposure-Response Analyses of Letermovir Following Oral and Intravenous Administration in Allogeneic Hematopoietic Cell Transplantation Recipients.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With Clinically-significant CMV Infection up to Week 24 Post-transplant |
37.5; 60.6 | <0.0001 sig |
| SECONDARY Time to Onset of Clinically-significant CMV Infection (Kaplan-Meier Estimate of Percentage of Participants With a Qualifying Event at Week 24 Post-transplant) |
18.9; 44.3 | <0.0001 sig |
| SECONDARY Percentage of Participants With Clinically-significant CMV Infection up to Week 14 Post-transplant |
19.1; 50.0 | <0.0001 sig |
| SECONDARY Percentage of Participants With CMV End-organ Disease up to Week 24 Post-transplant |
2.0; 2.4 | 0.4056 |
| SECONDARY Percentage of Participants With CMV End-organ Disease up to Week 14 Post-transplant |
0.4; 1.4 | 0.2258 |
| SECONDARY Percentage of Participants With Pre-emptive Therapy for CMV Viremia up to Week 14 Post-transplant |
18.8; 49.4 | <0.0001 sig |
| SECONDARY Percentage of Participants With Pre-emptive Therapy for CMV Viremia up to Week 24 Post-transplant |
36.6; 59.4 | <0.0001 sig |
| SECONDARY Time to Initiation of Pre-emptive Therapy for CMV Viremia (Kaplan-Meier Estimate of Percentage of Participants With a Qualifying Event at Week 24 Post-transplant) |
17.2; 42.4 | <0.0001 sig |
Eligibility Criteria
Inclusion Criteria
- Has documented seropositivity for CMV within 1 year before hematopoietic stem cell transplant (HSCT)
- Receiving first allogeneic HSCT (bone marrow, peripheral blood stem cell, or cord blood transplant)
- Female or male participant who is not of reproductive potential, or, if of reproductive potential, agrees to true abstinence or to use (or have their partner use) 2 acceptable methods of birth control from the time of consent through 90 days after the last dose of study drug
- Able to read, understand, and complete questionnaires and diaries
Exclusion Criteria
- Received a previous allogeneic HSCT (previous autologous HSCT is acceptable)
- History of CMV end-organ disease within 6 months before randomization
- Has evidence of CMV viremia (if tested) at any time from either signing of the Informed Consent Form or the HSCT procedure, whichever is earlier, until the time of randomization.
- Received the following within 7 days before screening or plans to receive during the study: ganciclovir, valganciclovir, foscarnet, acyclovir, valacyclovir, or famciclovir
- Received the following within 30 days before screening or plan to receive during the study: cidofovir, CMV hyper-immune globulin, any investigational CMV antiviral agent or biological therapy
- Has suspected or known hypersensitivity to ingredients of MK-8228 (letermovir) formulations
- Has severe hepatic insufficiency within 5 days before randomization
- Has end-stage renal impairment
- Has an uncontrolled infection on the day of randomization
- Requires mechanical ventilation or is hemodynamically unstable at the time of randomization
- Has documented positive results for human immunodeficiency virus (HIV) antibody, hepatitis C virus (HCV) antibody with detectable HCV ribonucleic acid, or hepatitis B surface antigen (HBsAg) within 90 days before randomization
- Has active solid tumor malignancies with the exception of localized basal cell or squamous cell skin cancer or the condition under treatment (for example, lymphoma)
- Is pregnant or expecting to conceive, is breastfeeding, or plans to breastfeed from the time of consent through 90 days after the last dose of study drug
- Is expecting to donate eggs or sperm from the time of consent through 90 days after the last dose of study drug
- Has participated in a study with an unapproved investigational compound (monoclonal antibodies are excepted) or device within 28 days of the first dose of study drug
- Has previously participated in a MK-8228 (letermovir) study
- Has, is, or is planning (during the study) to participate in any study involving administration of a CMV vaccine or another CMV investigational agent
- Is a user of recreational or illicit drugs or has a recent history (<=1 year) of drug or alcohol abuse or dependence
Data sourced from ClinicalTrials.gov (NCT02137772) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.