Skip to main content
OpenTrials
Completed

NCT Number: NCT02137772

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)

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Prevention of CMV Infection or Disease Disease Pathologic Processes Pathological Conditions, Signs and Symptoms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Letermovir

Drug

Letermovir 240 mg / 480 mg tablets, or 240 mg / 480 mg intravenous solution in 250 mL to be infused over 60 minutes.

Other names: MK-8228

Placebo

Drug

Placebo tablets, or intravenous solution in 250 mL to be infused over 60 minutes.

Primary outcomes

  1. 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

  1. Time to Onset of Clinically-significant CMV Infection (Kaplan-Meier Estimate of Percentage of Participants With a Qualifying Event at 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. 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.

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

    Time frame: Up to Week 14 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.

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

    Time frame: 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.

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

    Time frame: Up to Week 14 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.

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

    Time frame: 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.

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

    Time frame: Up to Week 24 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.

  7. 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)

    Time frame: Up to 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.

Other outcomes

  1. Percentage of Participants With One or More Adverse Events up to Week 48 Post-transplant

    Time frame: Up to Week 48 post-transplant

    An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event.

  2. Percentage of Participants Discontinued From Study Medication Due to an Adverse Event

    Time frame: Up to Week 14 post-transplant

    An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event.

Sponsors and collaborators

Lead sponsor

Merck Sharp & Dohme LLC

Industry

Registry information

Official study title

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

Important dates

Study start
2014
Primary completion
2016
Study completion
2016
First posted
May 14, 2014
Registry last updated
Sep 11, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.