Cytomegalovirus Infection
Conditions
Brief summary
The purpose of this study is to evaluate the efficacy and safety of a once-a-day oral or intravenous (IV) dose of Letermovir (MK-8228) in Chinese adult hematopoietic stem cell transplant (HSCT) recipients for the prevention of clinically significant cytomegalovirus (CMV) infection.
Interventions
DRUGLetermovir
Daily 240 mg or 480 mg oral tablets or IV dose
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
The key inclusion and
Exclusion criteria
include but are not limited to the following: Inclusion Criteria: * Male/Female Chinese adult participant of an allogeneic Hematopoietic Stem Cell Transplant (HSCT). * Has documented positive Cytomegalovirus (CMV) serostatus (CMV immunoglobulin G \[IgG\] seropositive) for recipient (R+) at the time of screening. * Is receiving a first allogeneic HSCT. * Is within 28 days post-HSCT at the time of randomization. * Female participant is not a Woman of Child Bearing Potential (WOCBP) or is a WOBCP who agrees to use acceptable contraception during the treatment period and for ≥28 days after the last dose of study drug.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Clinically Significant Cytomegalovirus (CMV) Infection up to Week 24 Post-Transplant | Up to Week 24 post-transplant (approximately 6 months) | Clinically significant CMV infection was defined as either one of the following: 1) initiation of anti-CMV pre-emptive therapy based on documented CMV viremia and the clinical condition of the participant or 2) onset of CMV end-organ disease. The percentage of participants with clinically significant CMV infection up to week 24 post-transplant is reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Discontinue Study Treatment Due to an Adverse Event | Up to 14 weeks | An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants who discontinued study treatment due to an AE is reported. |
| Percentage of Participants With Clinically Significant CMV Infection up to Week 14 Post-Transplant | Up to 14 weeks post-transplant (99 days) | Clinically significant CMV infection was defined as either one of the following: 1) initiation of anti-CMV pre-emptive therapy based on documented CMV viremia and the clinical condition of the participant or 2) onset of CMV end-organ disease. The percentage of participants with clinically significant CMV infection up to 14 weeks post-transplant is reported. |
| Percentage of Participants With Preemptive Therapy for CMV Viremia up to Week 14 Post-Transplant | Up to 14 weeks post-transplant (99 days) | Initiation of anti-CMV preemptive therapy was based on documented CMV viremia and the clinical condition of the participant. The percentage of participants with initiation of anti-CMV preemptive anti-CMV therapy up to 14 weeks post-transplant is reported. |
| Percentage of Participants With Preemptive Therapy for CMV Viremia up to Week 24 Post-Transplant | Up to 24 weeks post-transplant (approximately 6 months) | Initiation of anti-CMV preemptive therapy was based on documented CMV viremia and the clinical condition of the participant. The percentage of participants with initiation of anti-CMV preemptive anti-CMV therapy up to 24 weeks post-transplant is reported. |
| Percentage of Participants Who Experienced an Adverse Event (AE) | Up to 16 weeks | An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants who experienced an AE is reported. |
| Percentage of Participants With CMV End-organ Disease up to Week 24 Post-Transplant | Up to 24 weeks post-transplant (approximately 6 months) | CMV end-organ disease met per-protocol diagnostic criteria for CMV-pneumonia, gastrointestinal disease, hepatitis, central nervous system disease, retinitis, nephritis, cystitis, myocarditis, pancreatitis, or other disease categories. Only Clinical Adjudication Committee-confirmed CMV end-organ disease will be included in this analysis. The percentage of participants with CMV end-organ disease up to 24 weeks post-transplant is reported. |
| Percentage of Participants With All-Cause Mortality up to Week 14 Post-Transplant | Up to 14 weeks post-transplant (99 days) | The percentage of participants who died due to any cause up to 14 weeks post-transplant is reported. |
| Percentage of Participants With All-cause Mortality up to Week 24 Post-Transplant | Up to 24 weeks post-transplant (approximately 6 months) | The percentage of participants who died due to any cause up to 24 weeks post-transplant is reported. |
| Percentage of Participants With CMV End-organ Disease up to Week 14 Post-Transplant | Up to 14 weeks post-transplant (99 days) | CMV end-organ disease met per-protocol diagnostic criteria for CMV-pneumonia, gastrointestinal disease, hepatitis, central nervous system disease, retinitis, nephritis, cystitis, myocarditis, pancreatitis, or other disease categories. Only Clinical Adjudication Committee-confirmed CMV end-organ disease will be included in this analysis. The percentage of participants with CMV end-organ disease up to 14 weeks post-transplant is reported. |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Letermovir Chinese HSCT recipients received 240 mg of Letermovir \[for participants on Cyclosporin A (CsA)\] or 480 mg of Letermovir (for participants not on CsA) either orally or IV once daily through week 14 (99 days) post-transplant. | 120 |
| Total | 120 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 6 |
| Overall Study | Withdrawal by Parent/Guardian | 1 |
| Overall Study | Withdrawal by Subject | 6 |
Baseline characteristics
| Characteristic | Letermovir |
|---|---|
| Age, Continuous | 37.8 Years STANDARD_DEVIATION 12.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 120 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 120 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Sex: Female, Male Female | 45 Participants |
| Sex: Female, Male Male | 75 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 8 / 120 |
| other Total, other adverse events | 118 / 120 |
| serious Total, serious adverse events | 70 / 120 |
Outcome results
Primary
Percentage of Participants With Clinically Significant Cytomegalovirus (CMV) Infection up to Week 24 Post-Transplant
Clinically significant CMV infection was defined as either one of the following: 1) initiation of anti-CMV pre-emptive therapy based on documented CMV viremia and the clinical condition of the participant or 2) onset of CMV end-organ disease. The percentage of participants with clinically significant CMV infection up to week 24 post-transplant is reported.
Time frame: Up to Week 24 post-transplant (approximately 6 months)
Population: All allocated participants who received at least 1 dose of study treatment and have no detectable CMV viral deoxyribonucleic acid (DNA) when study intervention is initiated. Per protocol, participants who prematurely discontinued or had a missing outcome at the 24-week visit window were considered treatment failure (i.e. Non-completers equal failure \[NC=F\] approach was used).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Letermovir | Percentage of Participants With Clinically Significant Cytomegalovirus (CMV) Infection up to Week 24 Post-Transplant | 32 Percentage of Participants |
Secondary
Percentage of Participants Who Discontinue Study Treatment Due to an Adverse Event
An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants who discontinued study treatment due to an AE is reported.
Time frame: Up to 14 weeks
Population: All allocated participants who received at least one dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Letermovir | Percentage of Participants Who Discontinue Study Treatment Due to an Adverse Event | 0 Percentage of Participants |
Secondary
Percentage of Participants Who Experienced an Adverse Event (AE)
An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants who experienced an AE is reported.
Time frame: Up to 16 weeks
Population: All allocated participants who received at least one dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Letermovir | Percentage of Participants Who Experienced an Adverse Event (AE) | 99.2 Percentage of Participants |
Secondary
Percentage of Participants With All-Cause Mortality up to Week 14 Post-Transplant
The percentage of participants who died due to any cause up to 14 weeks post-transplant is reported.
Time frame: Up to 14 weeks post-transplant (99 days)
Population: All allocated participants who received at least 1 dose of study treatment and had no detectable CMV viral DNA when study intervention is initiated.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Letermovir | Percentage of Participants With All-Cause Mortality up to Week 14 Post-Transplant | 5.1 Percentage of Participants |
Secondary
Percentage of Participants With All-cause Mortality up to Week 24 Post-Transplant
The percentage of participants who died due to any cause up to 24 weeks post-transplant is reported.
Time frame: Up to 24 weeks post-transplant (approximately 6 months)
Population: All allocated participants who received at least 1 dose of study treatment and had no detectable CMV viral DNA when study intervention is initiated.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Letermovir | Percentage of Participants With All-cause Mortality up to Week 24 Post-Transplant | 6.1 Percentage of Participants |
Secondary
Percentage of Participants With Clinically Significant CMV Infection up to Week 14 Post-Transplant
Clinically significant CMV infection was defined as either one of the following: 1) initiation of anti-CMV pre-emptive therapy based on documented CMV viremia and the clinical condition of the participant or 2) onset of CMV end-organ disease. The percentage of participants with clinically significant CMV infection up to 14 weeks post-transplant is reported.
Time frame: Up to 14 weeks post-transplant (99 days)
Population: All allocated participants who received at least 1 dose of study treatment and had no detectable CMV viral DNA when study intervention is initiated. Per protocol, participants who prematurely discontinued or had a missing outcome at the 14-week visit window were considered treatment failure (i.e. Non-completers equal failure \[NC=F\] approach was used).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Letermovir | Percentage of Participants With Clinically Significant CMV Infection up to Week 14 Post-Transplant | 7.1 Percentage of Participants |
Secondary
Percentage of Participants With CMV End-organ Disease up to Week 14 Post-Transplant
CMV end-organ disease met per-protocol diagnostic criteria for CMV-pneumonia, gastrointestinal disease, hepatitis, central nervous system disease, retinitis, nephritis, cystitis, myocarditis, pancreatitis, or other disease categories. Only Clinical Adjudication Committee-confirmed CMV end-organ disease will be included in this analysis. The percentage of participants with CMV end-organ disease up to 14 weeks post-transplant is reported.
Time frame: Up to 14 weeks post-transplant (99 days)
Population: All allocated participants who received at least 1 dose of study treatment and had no detectable CMV viral DNA when study intervention is initiated. Per protocol, participants who prematurely discontinued or had a missing outcome at the 14-week visit window were considered treatment failure (i.e. Non-completers equal failure \[NC=F\] approach was used).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Letermovir | Percentage of Participants With CMV End-organ Disease up to Week 14 Post-Transplant | 6.1 Percentage of Participants |
Secondary
Percentage of Participants With CMV End-organ Disease up to Week 24 Post-Transplant
CMV end-organ disease met per-protocol diagnostic criteria for CMV-pneumonia, gastrointestinal disease, hepatitis, central nervous system disease, retinitis, nephritis, cystitis, myocarditis, pancreatitis, or other disease categories. Only Clinical Adjudication Committee-confirmed CMV end-organ disease will be included in this analysis. The percentage of participants with CMV end-organ disease up to 24 weeks post-transplant is reported.
Time frame: Up to 24 weeks post-transplant (approximately 6 months)
Population: All allocated participants who received at least 1 dose of study treatment and had no detectable CMV viral DNA when study intervention is initiated. Per protocol, participants who prematurely discontinued or had a missing outcome at the 24-week visit window were considered treatment failure (i.e. Non-completers equal failure \[NC=F\] approach was used).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Letermovir | Percentage of Participants With CMV End-organ Disease up to Week 24 Post-Transplant | 11.2 Percentage of Participants |
Secondary
Percentage of Participants With Preemptive Therapy for CMV Viremia up to Week 14 Post-Transplant
Initiation of anti-CMV preemptive therapy was based on documented CMV viremia and the clinical condition of the participant. The percentage of participants with initiation of anti-CMV preemptive anti-CMV therapy up to 14 weeks post-transplant is reported.
Time frame: Up to 14 weeks post-transplant (99 days)
Population: All allocated participants who received at least 1 dose of study treatment and had no detectable CMV viral DNA when study intervention is initiated. Per protocol, participants who prematurely discontinued or had a missing outcome at the 14-week visit window were considered treatment failure (i.e. Non-completers equal failure \[NC=F\] approach was used).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Letermovir | Percentage of Participants With Preemptive Therapy for CMV Viremia up to Week 14 Post-Transplant | 7.1 Percentage of Participants |
Secondary
Percentage of Participants With Preemptive Therapy for CMV Viremia up to Week 24 Post-Transplant
Initiation of anti-CMV preemptive therapy was based on documented CMV viremia and the clinical condition of the participant. The percentage of participants with initiation of anti-CMV preemptive anti-CMV therapy up to 24 weeks post-transplant is reported.
Time frame: Up to 24 weeks post-transplant (approximately 6 months)
Population: All allocated participants who received at least 1 dose of study treatment and had no detectable CMV viral DNA when study intervention is initiated. Per protocol, participants who prematurely discontinued or had a missing outcome at the 24-week visit window were considered treatment failure (i.e. Non-completers equal failure \[NC=F\] approach was used).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Letermovir | Percentage of Participants With Preemptive Therapy for CMV Viremia up to Week 24 Post-Transplant | 32.7 Percentage of Participants |