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Letermovir Versus Valganciclovir to Prevent Human Cytomegalovirus Disease in Kidney Transplant Recipients (MK-8228-002)

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ClinicalTrials.gov Identifier: NCT03443869
Recruitment Status : Recruiting
First Posted : February 23, 2018
Last Update Posted : February 22, 2019
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Brief Summary:
The primary objective of this study is to evaluate the efficacy of letermovir (LET) versus valganciclovir (VGCV) in preventing CMV disease in adult kidney transplant recipients. The primary hypotheses are that LET is non-inferior to VGCV; and if non-inferiority is demonstrated, that LET is superior to VGCV, in preventing CMV disease through 52 weeks post-transplant.

Condition or disease Intervention/treatment Phase
CMV Disease Drug: Letermovir Drug: Valganciclovir Drug: Acyclovir (ACV) Drug: Placebo to ACV Drug: Placebo to LET Drug: Placebo to VGCV Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 600 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Official Title: A Phase III, Randomized, Double-Blind, Active Comparator-Controlled Study to Evaluate the Efficacy and Safety of MK-8228 (Letermovir) Versus Valganciclovir for the Prevention of Human Cytomegalovirus (CMV) Disease in Adult Kidney Transplant Recipients
Actual Study Start Date : May 3, 2018
Estimated Primary Completion Date : September 19, 2021
Estimated Study Completion Date : September 19, 2021


Arm Intervention/treatment
Experimental: Letermovir
Letermovir (LET) 480mg (or 240 mg when co-administered with cyclosporin A) tablet orally; placebo to VGCV tablet orally once daily; and 400 mg capsule of acyclovir (ACV) orally every 12 hours for 28 weeks
Drug: Letermovir
LET 480mg (or 240 mg when co-administered with cyclosporin A) once daily for 28 weeks

Drug: Acyclovir (ACV)
400 mg over-encapsulated ACV tablet orally, every 12 hours for 28 weeks

Drug: Placebo to VGCV
Placebo to VGCV tablet orally, once daily for 28 weeks

Active Comparator: Valganciclovir
900 mg Valganciclovir (VGCV) tablet orally, once daily; placebo to LET tablet orally once daily; and placebo to ACV orally every 12 hours for 28 weeks
Drug: Valganciclovir
900 mg VGCV tablet orally, once daily for 28 weeks

Drug: Placebo to ACV
Over-encapsulated placebo tablet orally, every 12 hours for 28 weeks

Drug: Placebo to LET
Placebo to LET tablet orally, once daily for 28 weeks




Primary Outcome Measures :
  1. CMV Disease 52 Weeks [ Time Frame: Up to 52 weeks ]
    Percentage of participants with adjudicated CMV disease through 52 weeks post-transplant


Secondary Outcome Measures :
  1. CMV Disease 28 Weeks [ Time Frame: Up to 28 weeks ]
    Percentage of participants with adjudicated CMV disease through 28 weeks post-transplant

  2. Time To Onset [ Time Frame: Up to 52 weeks ]
    Time to onset of adjudicated CMV disease through 52 weeks post-transplant

  3. AE [ Time Frame: Up to week 30 ]
    Percentage of participants with any AE

  4. Drug-related Serious AE (SAE) [ Time Frame: Up to week 52 ]
    Percentage of participants with any drug-related SAE



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Have a documented negative serostatus for CMV within 180 days prior to randomization.
  • Anticipate receiving a primary or secondary allograft kidney from a CMV IgG seropositive (D+) donor at the time of screening AND have received a primary or secondary allograft kidney from a documented D+ donor at the time of randomization.
  • Be within 0 (i.e. day of transplantation) to 7 days (inclusive) post-kidney transplant at the time of randomization.
  • Males agree to use contraception during the treatment period, and for at least 90 days after the last dose of study treatment, and refrain from donating sperm during this period.
  • Female is not pregnant, not breastfeeding, and is not a woman of childbearing potential (WOCBP), OR if a WOCBP, agrees to follow the contraception guidance during the treatment period and for at least 90 days after the last dose of study treatment.

Exclusion Criteria:

  • Has received a previous solid organ transplant or hematopoietic stem cell transplant (HSCT). Note: Participants who have received a prior primary allograft kidney may be enrolled, provided that all other inclusion/exclusion criteria are met.
  • Is a multi-organ transplant recipient (e.g. kidney-pancreas). Double kidney transplant recipients (i.e. transplant of two kidneys from the same donor to the same recipient simultaneously) will be excluded.
  • Has a history of CMV disease or suspected CMV disease within 6 months prior to randomization.
  • Has suspected or known hypersensitivity to active or inactive ingredients of LET formulations, VGCV, GCV, and/or ACV formulations.
  • Is on dialysis at the time of randomization.
  • Has Child-Pugh Class C severe hepatic insufficiency at screening.
  • Has both moderate hepatic insufficiency AND moderate-to-severe renal insufficiency at screening.
  • Has any uncontrolled infection on the day of randomization.
  • Has documented positive results for human immunodeficiency virus antibody (HIV-Ab) test at any time prior to randomization, or for hepatitis C virus antibody (HCV-Ab) and with detectable HCV ribonucleic acid (RNA) within 90 days prior to randomization, or hepatitis B surface antigen (HBsAg) within 90 days prior to randomization.
  • Requires mechanical ventilation, or is hemodynamically unstable, at the time of randomization.
  • Has a history of malignancy ≤5 years prior to signing informed consent.
  • Is pregnant or expecting to conceive, is breastfeeding, or plans to breastfeed from the time of consent through at least 90 days following cessation of study therapy.
  • Is expecting to donate eggs or sperm starting from the time of consent through at least 90 days following cessation of study therapy.
  • Has received within 30 days prior to randomization or plans to receive during the study any of the following anti-CMV IgG antibody treatment or anti-CMV drug therapy including the following: Cidofovir, CMV hyper-immune globulin, Any investigational CMV antiviral agent/biologic therapy.
  • Has received within 7 days prior to randomization or plans to receive during the study any of the following anti-CMV drug therapy: LET, GCV, VGCV, Foscarnet, ACV, Valacyclovir, Famciclovir.
  • Is a user of recreational or illicit drugs or has had a recent history (within the last year) of drug or alcohol abuse or dependence.
  • Is currently participating or has participated in a study with an unapproved investigational compound or device within 28 days, or 5× half-life of the investigational compound whichever is longer, of initial dosing on this study.
  • Has previously participated in this study or any other study involving LET.
  • Has previously participated or is currently participating in any study involving administration of a CMV vaccine or another CMV investigational agent, or is planning to participate in a study of a CMV vaccine or another CMV investigational agent during the course of this study.

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): NCT03443869


Contacts
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Contact: Toll Free Number 1-888-577-8839 Trialsites@merck.com

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

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Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT03443869     History of Changes
Other Study ID Numbers: 8228-002
2017-001055-30 ( EudraCT Number )
MK-8228-002 ( Other Identifier: Merck Protocol Number )
First Posted: February 23, 2018    Key Record Dates
Last Update Posted: February 22, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php

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

Additional relevant MeSH terms:
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Valganciclovir
Acyclovir
Antiviral Agents
Anti-Infective Agents