Cytomegalovirus Infection Clinical Trial
Official title:
A Phase 3, Open-Label, Single-Arm Clinical Study to Evaluate the Safety, Efficacy and Pharmacokinetics of MK-8228 (Letermovir) for the Prevention of Human Cytomegalovirus (CMV) Infection and Disease in Adult Japanese Kidney Transplant Recipients
Verified date | September 2023 |
Source | Merck Sharp & Dohme LLC |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
This study aims to evaluate the safety, efficacy and pharmacokinetics (PK) of Letermovir (LET) administered as prevention of cytomegalovirus (CMV) infection and disease in adult Japanese kidney transplant recipients.
Status | Completed |
Enrollment | 22 |
Est. completion date | October 6, 2022 |
Est. primary completion date | October 6, 2022 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: - Meets recipient and/or donor CMV Immunoglobulin G (IgG) serostatus. - Anticipates receiving a primary or secondary allograft kidney at the time of screening and have received a primary or secondary allograft kidney at the time of allocation. - Is within 0 (i.e., day of transplantation) to 7 days (inclusive) post-kidney transplant at the time of allocation. - Is a Japanese male or female from 18 years to any years of age inclusive, at the time of signing the informed consent. - Female is not pregnant or breastfeeding, and is not a woman of childbearing potential (WOCBP); but if a WOCBP, she is using an acceptable contraceptive method, or is abstinent from heterosexual intercourse, and must have a negative highly sensitive pregnancy test within 72 hours before the first dose of study intervention. Exclusion Criteria: - Has received a previous solid organ transplant or hematopoietic stem cell transplant (HSCT). - Is a multi-organ transplant recipient (e.g., kidney-pancreas). - Has a history of CMV disease or suspected CMV disease within 6 months prior to allocation. - Has positive results on CMV assay and/or CMV antigen test at any time between the completion of the transplant surgery and time of allocation. - Has suspected or known hypersensitivity to active or inactive ingredients of LET formulations. - Is on dialysis (for the purposes of this protocol dialysis includes hemofiltration) or plasmapheresis at the time of allocation. - Has Child-Pugh Class C severe hepatic insufficiency at screening. - Has post-transplant renal function of creatinine clearance (CrCl) =10 mL/min at allocation (measured locally). - Has both moderate hepatic insufficiency AND moderate-to-severe renal insufficiency at screening. - Has any uncontrolled infection on the day of allocation. - Has documented positive results for human immunodeficiency virus antibody (HIV-Ab) test at any time prior to allocation, or for hepatitis C virus antibody (HCV-Ab) and with detectable HCV RNA within 90 days prior to allocation or hepatitis B surface antigen (HBsAg) within 90 days prior to allocation. - Requires mechanical ventilation, or is hemodynamically unstable, at the time of allocation. - Has a history of malignancy =5 years prior to signing informed consent. - Has received within 30 days prior to allocation or plans to receive during the study any of the following: CMV immune globulin; any investigational CMV antiviral agent/biologic therapy. - Has received any dose of LET prior to allocation. - Has received within 7 days prior to allocation or plans to receive during the study any anti-CMV drug therapy. - 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 taking or plans to take any of the prohibited medications listed in the protocol. - 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. - 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. - Is pregnant or expecting to conceive, is breastfeeding, or plans to breastfeed from the time of consent through at least 28 days following cessation of study therapy. - Is expecting to donate eggs starting from the time of consent through at least 28 days following cessation of study therapy. |
Country | Name | City | State |
---|---|---|---|
Japan | Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital ( Site 0002) | Nagoya | Aichi |
Japan | Sapporo City General Hospital ( Site 0004) | Sapporo | Hokkaido |
Japan | Osaka University Hospital ( Site 0003) | Suita | Osaka |
Japan | Tokyo Women's Medical University Hospital ( Site 0001) | Tokyo |
Lead Sponsor | Collaborator |
---|---|
Merck Sharp & Dohme LLC |
Japan,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Percentage of Participants With Adverse Events (AEs) | Percentage of participants with one or more adverse events (AEs) | Up to week 52 post-transplant | |
Primary | Percentage of Participants Who Discontinued From Study Drug Due to an AE | Percentage of participants who discontinued from study drug due to an AE | Up to week 28 post-transplant | |
Secondary | Percentage of Participants With Adjudicated CMV Disease or Undergone Anti-CMV Treatment | CMV disease was defined as the presence of either CMV end-organ disease or CMV syndrome and was confirmed by an independent, blinded Clinical Adjudication Committee (CAC). Only CAC-confirmed ("adjudicated") cases were included in percentage of participants who met the endpoint. Investigator-assessed cases which were not confirmed by the CAC were not included. Participants who have undergone anti-CMV treatment was defined as initiation of approved anti-CMV agents based on at least one positive cell on CMV antigenemia and/or quantifiable CMV DNA PCR assay performed locally. | Up to Week 52 post-transplant | |
Secondary | Percentage of Participants With Adjudicated CMV Disease | CMV disease was defined as the presence of either CMV end-organ disease or CMV syndrome and was confirmed by an independent, blinded Clinical Adjudication Committee (CAC). Only CAC-confirmed ("adjudicated") cases were included in percentage of participants who met the endpoint. Investigator-assessed cases which were not confirmed by the CAC were not included. | Up to Week 52 post-transplant | |
Secondary | Percentage of Participants With Quantifiable CMV DNAemia | Quantifiable CMV DNAemia (central) was defined as any case with a numeric value or >910,000,000 (not including reporting of PCR results as "detected, not quantifiable") using the Roche COBAS® AmpliPrep/COBAS TaqMan® (CAP/CTM) assay, which was performed by the central laboratory. | Up to Week 52 post-transplant | |
Secondary | Area Under the Concentration-time Curve During a Dosing Interval (AUCtau) of Plasma Letermovir-oral Treatment | AUCtau was defined as a measure of letermovir exposure that was calculated as the product of plasma drug concentration and time following an oral administration of letermovir. | Any day between Days 6-10: pre-dose, 1, 2.5, 5, 8 and 24 hrs post-dose | |
Secondary | Trough Concentration (Ctrough) of Plasma Letermovir - Oral Treatment | Ctrough was defined as the minimum concentration of letermovir that occurred immediately following an oral administration of letermovir. | Any day between Days 6-10: 24hrs post-dose | |
Secondary | Maximum Concentration (Cmax) of Plasma Letermovir - Oral Treatment | Cmax was defined as the maximum concentration of letermovir observed in plasma following an oral administration of letermovir. | Any day between Days 6-10: pre-dose, 1, 2.5, 5, 8 and 24 hrs post-dose | |
Secondary | Time to Reach Cmax (Tmax) of Plasma Letermovir - Oral Treatment | Tmax was defined as the time required post dosing to reach a maximum plasma concentration of letermovir following an oral administration of letermovir. | Any day between Days 6-10: pre-dose, 1, 2.5, 5, 8 and 24 hrs post-dose | |
Secondary | Apparent Clearance at Steady State (CLss/F) of Plasma Letermovir - Oral Treatment | Apparent clearance at steady state (CLss/F) of plasma letermovir following an oral administration of letermovir. | Any day between Days 6-10: pre-dose, 1, 2.5, 5, 8 and 24 hrs post-dose | |
Secondary | Area Under the Concentration-time Curve During a Dosing Interval (AUCtau) of Plasma Letermovir - IV Treatment | AUCtau was defined as a measure of letermovir exposure that was calculated as the product of plasma drug concentration and time following an IV administration of letermovir was intended to measure. | Any day between Days 6-10: pre-dose, 1, 2.5, 5, 8 and 24 hrs post-dose | |
Secondary | Trough Concentration (Ctrough) of Plasma Letermovir - IV Treatment | Ctrough was defined as the minimum concentration of letermovir that occurred immediately following an IV administration of letermovir was intended to measure. | Pre-dose on Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, 24 and 28 | |
Secondary | Concentration at the End of Infusion (Ceoi) of Plasma Letermovir - IV Treatment | Ceoi is defined as the amount of letermovir in plasma following an IV administration of letermovir was intended to measure. | Any day between Days 6-10: at end of infusion (1 hours post dose) | |
Secondary | Clearance at Steady State (CLss) of Plasma Letermovir - IV Treatment | Clearance at steady state (CLss) of plasma letermovir following an IV administration of letermovir was intended to measure. | Any day between Days 6-10: pre-dose, 1, 2.5, 5, 8 and 24 hrs post-dose |
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