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Trial record 1 of 2 for:    letermovir
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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)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02137772
First Posted: May 14, 2014
Last Update Posted: November 15, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
  Purpose
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.

Condition Intervention Phase
Prevention of CMV Infection or Disease Drug: Letermovir Drug: Placebo Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Official 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

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • 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 Outcome Measures:
  • 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 ]
    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.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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 Outcome Measures:
  • 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.

  • 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.


Enrollment: 570
Actual Study Start Date: June 6, 2014
Study Completion Date: November 21, 2016
Primary Completion Date: August 8, 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: Letermovir
Letermovir 240 mg / 480 mg tablets, or 240 mg / 480 mg intravenous solution in 250 mL to be infused over 60 minutes.
Other Name: MK-8228
Placebo Comparator: 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.
Drug: Placebo
Placebo tablets, or intravenous solution in 250 mL to be infused over 60 minutes.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02137772


Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT02137772     History of Changes
Other Study ID Numbers: 8228-001
2013-003831-31 ( EudraCT Number )
152923 ( Registry Identifier: JAPIC-CTI )
First Submitted: May 12, 2014
First Posted: May 14, 2014
Results First Submitted: October 16, 2017
Results First Posted: November 15, 2017
Last Update Posted: November 15, 2017
Last Verified: September 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Infection
Communicable Diseases
Cytomegalovirus Infections
Herpesviridae Infections
DNA Virus Infections
Virus Diseases