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

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.
 
ClinicalTrials.gov Identifier: NCT03443869
Recruitment Status : Active, not recruiting
First Posted : February 23, 2018
Last Update Posted : April 30, 2021
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Tracking Information
First Submitted Date  ICMJE February 19, 2018
First Posted Date  ICMJE February 23, 2018
Last Update Posted Date April 30, 2021
Actual Study Start Date  ICMJE May 3, 2018
Estimated Primary Completion Date April 7, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 19, 2018)
CMV Disease 52 Weeks [ Time Frame: Up to 52 weeks ]
Percentage of participants with adjudicated CMV disease through 52 weeks post-transplant
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 19, 2018)
  • CMV Disease 28 Weeks [ Time Frame: Up to 28 weeks ]
    Percentage of participants with adjudicated CMV disease through 28 weeks post-transplant
  • Time To Onset [ Time Frame: Up to 52 weeks ]
    Time to onset of adjudicated CMV disease through 52 weeks post-transplant
  • AE [ Time Frame: Up to week 30 ]
    Percentage of participants with any AE
  • Drug-related Serious AE (SAE) [ Time Frame: Up to week 52 ]
    Percentage of participants with any drug-related SAE
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Letermovir Versus Valganciclovir to Prevent Human Cytomegalovirus Disease in Kidney Transplant Recipients (MK-8228-002)
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Condition  ICMJE CMV Disease
Intervention  ICMJE
  • Drug: Letermovir
    LET 480mg (or 240 mg when co-administered with cyclosporin A) once daily for 28 weeks
  • Drug: Valganciclovir
    900 mg VGCV tablet orally, once daily for 28 weeks
  • Drug: Acyclovir (ACV)
    400 mg over-encapsulated ACV tablet orally, every 12 hours 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
  • Drug: Placebo to VGCV
    Placebo to VGCV tablet orally, once daily for 28 weeks
Study Arms  ICMJE
  • 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
    Interventions:
    • Drug: Letermovir
    • Drug: Acyclovir (ACV)
    • Drug: Placebo to VGCV
  • 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
    Interventions:
    • Drug: Valganciclovir
    • Drug: Placebo to ACV
    • Drug: Placebo to LET
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: February 19, 2018)
600
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 7, 2022
Estimated Primary Completion Date April 7, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 or plasmapheresis at the time of randomization. Dialysis includes hemofiltration.
  • 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany,   Argentina,   Australia,   Austria,   Belgium,   Canada,   Colombia,   France,   Hungary,   Italy,   Mexico,   New Zealand,   Poland,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03443869
Other Study ID Numbers  ICMJE 8228-002
2017-001055-30 ( EudraCT Number )
MK-8228-002 ( Other Identifier: Merck Protocol Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php
Responsible Party Merck Sharp & Dohme Corp.
Study Sponsor  ICMJE Merck Sharp & Dohme Corp.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Merck Sharp & Dohme Corp.
PRS Account Merck Sharp & Dohme Corp.
Verification Date April 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP