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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03443869




Registration number
NCT03443869
Ethics application status
Date submitted
19/02/2018
Date registered
23/02/2018

Titles & IDs
Public title
Letermovir Versus Valganciclovir to Prevent Human Cytomegalovirus Disease in Kidney Transplant Recipients (MK-8228-002)
Scientific 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
Secondary ID [1] 0 0
MK-8228-002
Secondary ID [2] 0 0
8228-002
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
CMV Disease 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Letermovir
Treatment: Drugs - Valganciclovir
Treatment: Drugs - Acyclovir (ACV)
Treatment: Drugs - Placebo to ACV
Treatment: Drugs - Placebo to LET
Treatment: Drugs - Placebo to VGCV

Experimental: Letermovir - LET 480mg (or 240 mg when administered concomitantly 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

Active comparator: Valganciclovir - 900 mg VGCV tablet orally, once daily; placebo to LET tablet orally once daily; and placebo to ACV orally every 12 hours for 28 weeks


Treatment: Drugs: Letermovir
LET 480mg (or 240 mg when administered concomitantly with cyclosporin A) once daily for 28 weeks

Treatment: Drugs: Valganciclovir
900 mg VGCV tablet orally, once daily for 28 weeks

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

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

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

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

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With Adjudicated Cytomegalovirus (CMV) Disease Through 52 Weeks Post-transplant
Timepoint [1] 0 0
Up to 52 weeks
Secondary outcome [1] 0 0
Percentage of Participants With Adjudicated CMV Disease Through 28 Weeks Post-transplant
Timepoint [1] 0 0
Up to 28 weeks
Secondary outcome [2] 0 0
Time to Onset of Adjudicated CMV Disease Through 52 Weeks Post-transplant
Timepoint [2] 0 0
Up to 52 weeks
Secondary outcome [3] 0 0
Percentage of Participants With Any AE
Timepoint [3] 0 0
Up to 52 weeks
Secondary outcome [4] 0 0
Percentage of Participants With Any Drug-related Serious Adverse Event (SAE)
Timepoint [4] 0 0
Up to 52 weeks

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital ( Site 0005) - Camperdown
Recruitment hospital [2] 0 0
Westmead Hospital ( Site 0006) - Westmead
Recruitment hospital [3] 0 0
Princess Alexandra Hospital ( Site 0004) - Woolloongabba
Recruitment hospital [4] 0 0
Royal Adelaide Hospital ( Site 0003) - Adelaide
Recruitment hospital [5] 0 0
Monash Health-Monash Medical Centre ( Site 0008) - Clayton
Recruitment hospital [6] 0 0
Royal Melbourne Hospital ( Site 0007) - Parkville
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [4] 0 0
5000 - Adelaide
Recruitment postcode(s) [5] 0 0
3168 - Clayton
Recruitment postcode(s) [6] 0 0
3050 - Parkville
Recruitment outside Australia
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United States of America
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Alabama
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California
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Georgia
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Illinois
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Indiana
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Louisiana
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Maryland
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Massachusetts
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Michigan
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Nebraska
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New Jersey
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New York
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North Carolina
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Ohio
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Pennsylvania
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South Carolina
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Tennessee
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Virginia
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Washington
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Buenos Aires
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Caba
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Corrientes
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Tirol
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Wien
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Paris
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Germany
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Nordrhein-Westfalen
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Germany
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Berlin
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Hungary
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Baranya
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Hungary
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Csongrad
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Hungary
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Budapest
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Hungary
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Debrecen
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Piemonte
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Veneto
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Milano
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Roma
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Mexico
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Morelos
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Mexico
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Aguascalientes
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Mexico
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Ciudad de Mexico
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Mexico
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Mexico City
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Mexico
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Veracruz
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New Zealand
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Auckland
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Dolnoslaskie
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Mazowieckie
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Pomorskie
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La Coruna
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Zaragoza
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United Kingdom
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London, City Of
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United Kingdom
State/province [70] 0 0
Birmingham

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Merck Sharp & Dohme LLC
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: http://engagezone.msd.com/ds_documentation.php


What supporting documents are/will be available?

Results publications and other study-related documents

TypeCitations or Other Details
Journal Limaye AP, Budde K, Humar A, Vincenti F, Kuypers D... [More Details]