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)

Merck Sharp & Dohme LLC570 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

DOUBLE

Enrollment

570

Conditions

Prevention of CMV Infection or Disease

Interventions

LetermovirDRUG

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Percentage of Participants With Clinically-significant CMV Infection up to Week 24 Post-transplant

Time frame: Up to Week 24 post-transplant

Secondary Outcomes

Time to Onset of Clinically-significant CMV Infection (Kaplan-Meier Estimate of Percentage of Participants With a Qualifying Event at Week 24 Post-transplant)

Clinically-significant CMV infection was defined as either one of the following: 1) onset of CMV end-organ disease, or 2) initiation of anti-CMV pre-emptive therapy based on documented CMV viremia and the clinical condition of the participant. Time to onset of clinically-significant CMV infection was defined from the day of transplantation to the day the participant developed clinically-significant CMV infection, and was analyzed by the Kaplan-Meier method. Participants were censored at the last assessment for participants who discontinued or did not develop clinically-significant CMV infection.

Time frame: Up to Week 24 post-transplant

Percentage of Participants With Clinically-significant CMV Infection up to Week 14 Post-transplant

Time frame: Up to Week 14 post-transplant

Percentage of Participants With CMV End-organ Disease up to Week 24 Post-transplant

CMV end-organ disease met per-protocol diagnostic criteria for CMV-pneumonia, gastrointestinal disease, hepatitis, central nervous system disease, retinitis, nephritis, cystitis, myocarditis, pancreatitis, or other disease categories. Only Clinical Adjudication Committee-confirmed CMV end-organ disease was included in this analysis. The percentage of participants with CMV end-organ disease was assessed.

Time frame: Up to Week 24 post-transplant

Percentage of Participants With CMV End-organ Disease up to Week 14 Post-transplant

Time frame: Up to Week 14 post-transplant

Percentage of Participants With Pre-emptive Therapy for CMV Viremia up to Week 14 Post-transplant

Initiation of anti-CMV pre-emptive therapy was based on documented CMV viremia and the clinical condition of the participant. The percentage of participants with initiation of anti-CMV pre-emptive anti-CMV therapy was assessed.

Time frame: Up to Week 14 post-transplant

Percentage of Participants With Pre-emptive Therapy for CMV Viremia up to Week 24 Post-transplant

Time frame: Up to Week 24 post-transplant

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)

The need for anti-CMV pre-emptive therapy was based on documented CMV viremia and the clinical condition of the participant. The outcome was calculated from the day of transplantation to the start of anti-CMV pre-emptive therapy, and was analyzed by the Kaplan-Meier method. Participants were censored at the last assessment for participants who discontinued or did not initiate pre-emptive therapy.

Time frame: Up to Week 24 post-transplant