A Phase III Randomized, Placebo-controlled Clinical Trial to Evaluate the Safety and Efficacy of MK-8228 (Letermovir) for the Prevention of Clinically Significant Human Cytomegalovirus (CMV) Infection in Adult, CMV-Seropositive Allogeneic Hematopoietic Stem Cell Transplant Recipients
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Merck Sharp & Dohme LLC
- Enrollment
- 570
- Primary Endpoint
- Percentage of Participants With Clinically-significant CMV Infection up to Week 24 Post-transplant
Study Overview
Brief 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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
Letermovir
Letermovir oral or intravenous (IV) formulation was administered once daily for up to 14 weeks, beginning up to Day 28 days post-transplant. The dose was 240 mg once daily for participants receiving concomitant cyclosporin A and 480 mg once daily for participants not receiving cyclosporin A. Intravenous infusion was administered only to participants who are unable to swallow tablets or who have a condition that may interfere with absorption of the tablets.
Intervention: Letermovir (Drug)
Placebo
Placebo oral or IV formulation was administered once daily for up to 14 weeks, beginning up to Day 28 post-transplant. The number of placebo tablets was to mimic that for letermovir administration according to the concomitant cyclosporin A status. Intravenous infusion was administered only to participants who are unable to swallow tablets or who have a condition that may interfere with absorption of the tablets.
Intervention: Placebo (Drug)
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
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. The percentage of participants with clinically-significant CMV infection was assessed.
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)(Up to Week 24 post-transplant)
- Percentage of Participants With Clinically-significant CMV Infection up to Week 14 Post-transplant(Up to Week 14 post-transplant)
- Percentage of Participants With CMV End-organ Disease up to Week 24 Post-transplant(Up to Week 24 post-transplant)
- Percentage of Participants With CMV End-organ Disease up to Week 14 Post-transplant(Up to Week 14 post-transplant)
- Percentage of Participants With Pre-emptive Therapy for CMV Viremia up to Week 14 Post-transplant(Up to Week 14 post-transplant)
- Percentage of Participants With Pre-emptive Therapy for CMV Viremia up to Week 24 Post-transplant(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)(Up to Week 24 post-transplant)