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 (MSD)

Status and phase: Completed; Phase 3

Conditions: Prevention of CMV Infection or Disease

Treatments: Drug: Placebo; Drug: Letermovir

Study type: Interventional

Funder types: Industry

Identifiers

NCT02137772

2013-003831-31 (EudraCT Number)

152923 (Registry Identifier)

8228-001

Details and patient eligibility

About

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.

Enrollment: 570 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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570 participants in 2 patient groups, including a placebo group

Letermovir

Experimental group

Description:

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.

Treatment:

Drug: Letermovir

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo