Cytomegalovirus InfectionPhase 3NCT04129398
MK-8228 (Letermovir) in the Prevention of Human Cytomegalovirus (CMV) Infection and Disease in Adult Japanese Kidney Transplant Recipients (MK-8228-042)
A Phase 3 study testing Letermovir tablet and Letermovir IV in people with Cytomegalovirus Infection and Cytomegalovirus Disease, run by Merck Sharp & Dohme LLC at 4 sites in Japan.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cytomegalovirus Infection, Cytomegalovirus Disease
- What is being tested?
- Letermovir tablet and Letermovir IV
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 4 sitesJapan
- Study dates
- 27 Dec 2019to 6 Oct 2022
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
4 sites in 1 country.
Japan4 sites
Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital ( Site 0002)
Nagoya, Aichi-ken, 466-8650
Sapporo City General Hospital ( Site 0004)
Sapporo, Hokkaido, 060-8604
Osaka University Hospital ( Site 0003)
Suita, Osaka, 565-0871
Tokyo Women's Medical University Hospital ( Site 0001)
Tokyo, 162-8666
About this study
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
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.
- Conditions
- Cytomegalovirus Infection, Cytomegalovirus Disease
- Being tested
- Letermovir tablet, Letermovir IV
- Medical subject headings
- Cytomegalovirus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Letermovir tabletDrug
Also called MK-8228, PREVYMIS®
A single 240 mg tablet or two 240 mg tablets letermovir administered orally, once daily for 28 weeks
Letermovir IVDrug
Also called MK-8228, PREVYMIS®
IV solution of 240 mg (one vial) or 480 mg (2 vials) letermovir in 250 mL infused over 60 minutes, once daily for 28 weeks
| Study group | Role | What they receive |
|---|---|---|
| Letermovir | Experimental | Letermovir oral or intravenous (IV) formulation will be administered once daily for up to 28 weeks, beginning up to 7 days post-transplant. The dose will be 240 mg once daily for participants receiving concomitant cyclosporin A (CsA) and 480 mg once daily for participants not receiving CsA. IV infusion will be administered only to participants who are unable to swallow tablets or who have a condition that may interfere with absorption of the tablets. Receives: Drug: Letermovir tablet; Drug: Letermovir IV |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Adverse Events (AEs)
Percentage of participants with one or more adverse events (AEs)
Measured: Up to week 52 post-transplant
Percentage of Participants Who Discontinued From Study Drug Due to an AE
Percentage of participants who discontinued from study drug due to an AE
Measured: Up to week 28 post-transplant
Secondary outcomes (12)
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.
Measured: Up to Week 52 post-transplant
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.
Measured: Up to Week 52 post-transplant
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.
Measured: Up to Week 52 post-transplant
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.
Measured: Any day between Days 6-10: pre-dose, 1, 2.5, 5, 8 and 24 hrs post-dose
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.
Measured: Any day between Days 6-10: 24hrs post-dose
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.
Measured: Any day between Days 6-10: pre-dose, 1, 2.5, 5, 8 and 24 hrs post-dose
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.
Measured: Any day between Days 6-10: pre-dose, 1, 2.5, 5, 8 and 24 hrs post-dose
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.
Measured: Any day between Days 6-10: pre-dose, 1, 2.5, 5, 8 and 24 hrs post-dose
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.
Measured: Any day between Days 6-10: pre-dose, 1, 2.5, 5, 8 and 24 hrs post-dose
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.
Measured: Pre-dose on Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, 24 and 28
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.
Measured: Any day between Days 6-10: at end of infusion (1 hours post dose)
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.
Measured: Any day between Days 6-10: pre-dose, 1, 2.5, 5, 8 and 24 hrs post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Oct 2019
- Study start27 Dec 2019
- Primary completion6 Oct 2022
- Study completion6 Oct 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cytomegalovirus InfectionStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04129398
- Sponsor's protocol ID
- 8228-042
- Other IDs
- MK-8228-042, 195020
- Status last verified
- Jul 2024
- First submitted
- 15 Oct 2019
- Last updated
- 21 Aug 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Publications
Ishida H, Goto N, Imamura R, Sasaki H, Unagami K, Futamura K, Murata Y, Oshima N, Eto T, Haber B. Letermovir safety and efficacy for cytomegalovirus prophylaxis in adult Japanese kidney transplant recipients: a multicenter, open-label, noncomparative Phase 3 study. Clin Exp Nephrol. 2024 Aug;28(8):822-831. doi: 10.1007/s10157-024-02471-0. Epub 2024 Apr 13.
PubMed 38615067
Study at a glance
From the registry record, last updated by the sponsor on 21 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04129398
- Acronym / sponsor ID
- 8228-042
- Conditions
- Cytomegalovirus Infection, Cytomegalovirus Disease
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 27 Dec 2019 (actual)
- Primary completion
- 6 Oct 2022 (actual)
- Study completion
- 6 Oct 2022 (actual)
- First posted
- 16 Oct 2019 (actual)
- Results
- Posted 1 Apr 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Letermovir | Experimental | Drug: Letermovir tablet, Drug: Letermovir IVLetermovir oral or intravenous (IV) formulation will be administered once daily for up to 28 weeks, beginning up to 7 days post-transplant. The dose will be 240 mg once daily for participants receiving concomitant cyclosporin A (CsA) and 480 mg once daily for participants not receiving CsA. IV infusion will be administered only to participants who are unable to swallow tablets or who have a condition that may interfere with absorption of the tablets. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (23 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Letermovir tabletAlso: MK-8228, PREVYMIS®A single 240 mg tablet or two 240 mg tablets letermovir administered orally, once daily for 28 weeks | Drug | Letermovir |
| Letermovir IVAlso: MK-8228, PREVYMIS®IV solution of 240 mg (one vial) or 480 mg (2 vials) letermovir in 250 mL infused over 60 minutes, once daily for 28 weeks | Drug | Letermovir |
Primary outcome
Percentage of Participants With Adverse Events (AEs)
Time frame: Up to week 52 post-transplant
Percentage of participants with one or more adverse events (AEs)
Percentage of Participants Who Discontinued From Study Drug Due to an AE
Time frame: Up to week 28 post-transplant
Percentage of participants who discontinued from study drug due to an AE
12 secondary outcomes
Percentage of Participants With Adjudicated CMV Disease or Undergone Anti-CMV Treatment
Time frame: Up to Week 52 post-transplant
Percentage of Participants With Adjudicated CMV Disease
Time frame: Up to Week 52 post-transplant
Percentage of Participants With Quantifiable CMV DNAemia
Time frame: Up to Week 52 post-transplant
Area Under the Concentration-time Curve During a Dosing Interval (AUCtau) of Plasma Letermovir-oral Treatment
Time frame: Any day between Days 6-10: pre-dose, 1, 2.5, 5, 8 and 24 hrs post-dose
Trough Concentration (Ctrough) of Plasma Letermovir - Oral Treatment
Time frame: Any day between Days 6-10: 24hrs post-dose
Maximum Concentration (Cmax) of Plasma Letermovir - Oral Treatment
Time frame: Any day between Days 6-10: pre-dose, 1, 2.5, 5, 8 and 24 hrs post-dose
Time to Reach Cmax (Tmax) of Plasma Letermovir - Oral Treatment
Time frame: Any day between Days 6-10: pre-dose, 1, 2.5, 5, 8 and 24 hrs post-dose
Apparent Clearance at Steady State (CLss/F) of Plasma Letermovir - Oral Treatment
Time frame: Any day between Days 6-10: pre-dose, 1, 2.5, 5, 8 and 24 hrs post-dose
Area Under the Concentration-time Curve During a Dosing Interval (AUCtau) of Plasma Letermovir - IV Treatment
Time frame: Any day between Days 6-10: pre-dose, 1, 2.5, 5, 8 and 24 hrs post-dose
Trough Concentration (Ctrough) of Plasma Letermovir - IV Treatment
Time frame: Pre-dose on Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, 24 and 28
Concentration at the End of Infusion (Ceoi) of Plasma Letermovir - IV Treatment
Time frame: Any day between Days 6-10: at end of infusion (1 hours post dose)
Clearance at Steady State (CLss) of Plasma Letermovir - IV Treatment
Time frame: Any day between Days 6-10: pre-dose, 1, 2.5, 5, 8 and 24 hrs post-dose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Aug 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 38615067Ishida H, Goto N, Imamura R, Sasaki H, Unagami K, Futamura K, Murata Y, Oshima N, Eto T, Haber B. Letermovir safety and efficacy for cytomegalovirus prophylaxis in adult Japanese kidney transplant recipients: a multicenter, open-label, noncomparative Phase 3 study. Clin Exp Nephrol. 2024 Aug;28(8):822-831. doi: 10.1007/s10157-024-02471-0. Epub 2024 Apr 13.
- Merck Clinical Trials InformationLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Merck Sharp & Dohme LLC
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Letermovir tablet and Letermovir IV in people with Cytomegalovirus Infection and Cytomegalovirus Disease, run by Merck Sharp & Dohme LLC at 4 sites in Japan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Apr 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Adverse Events (AEs) (time frame: Up to week 52 post-transplant). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04129398, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Aug 2024.