Extension of Letermovir (LET) From Day 100 to Day 200 Pos... | NCT03930615

ID	Type	Description
MK-8228-040	Other Identifier	Merck Sharp & Dohme Corp.
194797	Registry Identifier	JAPIC-CTI
2018-001038-17	EudraCT Number

Label	Type	Description	Intervention Names
Letermovir	Experimental	Participants who received HSCT transplant and 100 days of LET prophylaxis were randomized to an additional 100 days of LET (480 mg once daily alone or 240 mg once daily for participants on cyclosporin A) treatment.	Drug: Letermovir
Placebo	Placebo Comparator	Participants who received HSCT transplant and 100 days of LET prophylaxis were randomized to an additional 100 days of placebo treatment.	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Letermovir	Drug	LET tablet or intravenous infusion at a total daily dose of 240 mg (when given with cyclosporin A) or 480 mg (when given alone).	Letermovir

Measure	Description	Time Frame
Percentage of Participants With Clinically Significant CMV Infection From Week 14 (~100 Days) Post-transplant Through Week 28 (~200 Days) Post-transplant	Clinically significant CMV infection is either the onset of probable or proven CMV end-organ disease or initiation of anti-CMV preemptive therapy (PET) with approved anti-CMV agents (ganciclovir, valganciclovir, foscarnet, and/or cidofovir) based on documented CMV viremia and the clinical condition of the participant. Missing values were handled by the observed failure (OF) approach where failure was defined as all participants who develop clinically significant CMV infection or discontinue prematurely from the study with CMV viremia from week 14 (~100 days) through week 28 post-transplant. It was hypothesized that LET is superior to placebo in the prevention of clinically significant CMV infection when LET prophylaxis is extended from 100 to 200 days.	From Week 14 post-transplant to Week 28 post-transplant (approximately 14 weeks)

Measure	Description	Time Frame
Percentage of Participants Experiencing ≥1 Adverse Events (AEs) From Week 14 (~100 Days) Post-transplant Through Week 28 (~200 Days) Post-transplant	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.	From Week 14 post-transplant to Week 28 post-transplant (approximately 14 weeks)

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

have documented positive CMV serostatus (CMV immunoglobulin G [IgG] seropositive) for recipient (R+) at the time of transplant
has a history of allogeneic HSCT (bone marrow, peripheral blood stem cell, or cord blood transplant) within ~100 days prior to randomization
has undetectable CMV deoxyribonucleic acid (DNA) or detectable/not quantifiable CMV DNA from a plasma sample collected within 14 days prior to randomization
has received LET as primary prophylaxis that started within 28 days of HSCT and continued through Week 14 post-transplant (± 1 week) prior to randomization
is at high risk of CMV disease, defined as meeting one or more of the following criteria:
has a related donor with at least 1 mismatch at 1 of the specified 3 human leukocyte antigen (HLA) gene loci (HLA-A, B, or DR)
has an unrelated donor with at least one mismatch at one of the specified four HLA gene loci (HLA-A, B, C, and DRB1)
has a haploidentical donor
has umbilical cord blood as the stem-cell source
has ex-vivo T-cell-depleted grafts
has received anti-thymocyte globulin
has received alemtuzumab
has graft versus host disease (GVHD) or other conditions, requiring the use of systemic prednisone (or equivalent) at a dose of ≥1 mg/kg of body weight per day within 6 weeks of randomization
for female participants, is not pregnant or breastfeeding, and is either not a woman of childbearing 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.

Exclusion Criteria:

has a history of CMV end-organ disease or preemptive treatment therapy for CMV after HSCT prior to randomization
has a history of >14 days total of LET interruption during the first 100 days post-transplant prior to randomization
has suspected or known hypersensitivity to active or inactive ingredients of LET formulations
has severe hepatic insufficiency defined as Child-Pugh Class C within 14 days prior to randomization.
has serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >5× the upper limit of normal (ULN) within 14 days prior to randomization
has end-stage renal impairment with a creatinine clearance less than 10 mL/min, as calculated by the Cockcroft-Gault equation using serum creatinine within 14 days prior to randomization
has both moderate hepatic insufficiency AND moderate-to-severe renal insufficiency
has an uncontrolled infection on the day of enrollment
requires mechanical ventilation or is hemodynamically unstable at the time of enrollment
has a documented positive result for a human immunodeficiency virus antibody (HIV-Ab) test at any time prior to screening, or for hepatitis C virus antibody (HCV-Ab) with detectable HCV ribonucleic acid (RNA), or hepatitis B surface antigen (HBsAg) within 6 months prior to screening.
has active solid tumor malignancies with the exception of localized basal cell or squamous cell skin cancer or the condition under treatment (eg, lymphomas)
has received cidofovir or CMV immunoglobulin with 30 days prior to screening
is currently participating or has participated in a study with an unapproved investigational compound, monoclonal antibody, or device within 28 days or 5× half-life of the investigational compound or monoclonal antibody, whichever is longer, of initial dosing in this study
has previously participated in this study or any other study involving LET, 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 28 days after the last dose of study therapy
is expecting to donate eggs starting from the time of consent through 28 days after the last dose of study therapy
has clinically relevant drug or alcohol abuse within 12 months of screening that may interfere with participant treatment, assessment, or compliance with the protocol as assessed by the investigator
has a history or current evidence of any condition, therapy, lab abnormality, or other circumstance that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or would be put at undue risk as judged by the investigator, such that it is not in the best interest of the participant to participate in this study

Name	Affiliation	Role
Medical Director	Merck Sharp & Dohme LLC	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
City of Hope National Medical Center ( Site 0158)		Duarte	California	91010	United States
University of California Davis Medical Center ( Site 0156)

PubMed Identifier	Type	Citation	Retractions
38142695	Result	Russo D, Schmitt M, Pilorge S, Stelljes M, Kawakita T, Teal VL, Haber B, Bopp C, Dadwal SS, Badshah C. Efficacy and safety of extended duration letermovir prophylaxis in recipients of haematopoietic stem-cell transplantation at risk of cytomegalovirus infection: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Haematol. 2024 Feb;11(2):e127-e135. doi: 10.1016/S2352-3026(23)00344-7. Epub 2023 Dec 21.
36464218

ID	Title	Description
FG000	Letermovir	Participants who received HSCT transplant and 100 days of LET prophylaxis were randomized to an additional 100 days of LET (480 mg once daily alone or 240 mg once daily for participants on cyclosporin A) treatment.
FG001	Placebo

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jan 10, 2020	Oct 5, 2022

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percentage of Participants With Clinically Significant CMV Infection From Week 14 (~100 Days) Post-transplant Through Week 28 (~200 Days) Post-transplant

Clinically significant CMV infection is either the onset of probable or proven CMV end-organ disease or initiation of anti-CMV preemptive therapy (PET) with approved anti-CMV agents (ganciclovir, valganciclovir, foscarnet, and/or cidofovir) based on documented CMV viremia and the clinical condition of the participant. Missing values were handled by the observed failure (OF) approach where failure was defined as all participants who develop clinically significant CMV infection or discontinue prematurely from the study with CMV viremia from week 14 (~100 days) through week 28 post-transplant. It was hypothesized that LET is superior to placebo in the prevention of clinically significant CMV infection when LET prophylaxis is extended from 100 to 200 days.

All randomized participants who received at least 1 dose of study intervention.

Posted

Number

Percentage of participants

From Week 14 post-transplant to Week 28 post-transplant (approximately 14 weeks)

ID	Title	Description
OG000	Letermovir	Participants who received HSCT transplant and 100 days of LET prophylaxis were randomized to an additional 100 days of LET (480 mg once daily alone or 240 mg once daily for participants on cyclosporin A) treatment.
OG001	Placebo	Participants who received HSCT transplant and 100 days of LET prophylaxis were randomized to an additional 100 days of placebo treatment.

Units	Counts
Participants	OG000144 OG00174

Title

Denominators

Categories

Title	Measurements
	OG0002.8 OG00118.9

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	It was hypothesized that LET is superior to placebo in the prevention of clinically significant CMV infection.	Mantel Haenszel	Stratum adjusted	0.0005	A one-sided p-value ≤0.0249 was used for declaring statistical significance	Treatment Difference	-16.1			2-Sided	95	-25.8	-6.5			Letermovir minus placebo		Superiority

Secondary

Percentage of Participants Experiencing ≥1 Adverse Events (AEs) From Week 14 (~100 Days) Post-transplant Through Week 28 (~200 Days) Post-transplant

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.

All randomized participants who received at least 1 dose of study intervention according to the study intervention they received.

Posted

Number

Percentage of participants

From Week 14 post-transplant to Week 28 post-transplant (approximately 14 weeks)

ID	Title	Description
OG000	Letermovir	Participants who received HSCT transplant and 100 days of LET prophylaxis were randomized to an additional 100 days of LET (480 mg once daily alone or 240 mg once daily for participants on cyclosporin A) treatment.
OG001	Placebo	Participants who received HSCT transplant and 100 days of LET prophylaxis were randomized to an additional 100 days of placebo treatment.

Units	Counts
Participants

Secondary

Percentage of Participants Withdrawing From Study Drug Due to an AE From Week 14 (~100 Days) Post-transplant Through Week 28 (~200 Days) Post-transplant

An 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.

All randomized participants who received at least 1 dose of study intervention according to the study intervention they received.

Posted

Number

Percentage of participants

From Week 14 post-transplant to Week 28 post-transplant (approximately 14 weeks)

ID	Title	Description
OG000	Letermovir	Participants who received HSCT transplant and 100 days of LET prophylaxis were randomized to an additional 100 days of LET (480 mg once daily alone or 240 mg once daily for participants on cyclosporin A) treatment.
OG001	Placebo	Participants who received HSCT transplant and 100 days of LET prophylaxis were randomized to an additional 100 days of placebo treatment.

Units	Counts
Participants

Secondary

Percentage of Participants With Clinically Significant CMV Infection From Week 14 Post-transplant Through Week 38 Post-transplant

Clinically significant CMV infection is either the onset of probable or proven CMV end-organ disease or initiation of anti-CMV PET with approved anti-CMV agents (ganciclovir, valganciclovir, foscarnet, and/or cidofovir) based on documented CMV viremia and the clinical condition of the participant. Missing values were handled by the OF approach where failure was defined as all participants who develop clinically significant CMV infection or discontinue prematurely from the study with CMV viremia from week 14 (~100 days) through week 38 post-transplant.

All randomized participants who received at least 1 dose of study intervention.

Posted

Number

Percentage of participants

From Week 14 post-transplant to Week 38 post-transplant (approximately 24 weeks)

ID	Title	Description
OG000	Letermovir	Participants who received HSCT transplant and 100 days of LET prophylaxis were randomized to an additional 100 days of LET (480 mg once daily alone or 240 mg once daily for participants on cyclosporin A) treatment.
OG001	Placebo	Participants who received HSCT transplant and 100 days of LET prophylaxis were randomized to an additional 100 days of placebo treatment.

Secondary

Percentage of Participants With Clinically Significant CMV Infection From Week 14 Post-transplant Through Week 48 Post-transplant

All randomized participants who received at least 1 dose of study intervention.

Posted

Number

Percentage of participants

From Week 14 post-transplant to Week 48 post-transplant (approximately 34 weeks)

ID	Title	Description
OG000	Letermovir	Participants who received HSCT transplant and 100 days of LET prophylaxis were randomized to an additional 100 days of LET (480 mg once daily alone or 240 mg once daily for participants on cyclosporin A) treatment.
OG001	Placebo	Participants who received HSCT transplant and 100 days of LET prophylaxis were randomized to an additional 100 days of placebo treatment.

Secondary

Time to Onset of Clinically Significant CMV Infection From Week 14 Post-transplant to Week 28 Post-transplant

Clinically significant CMV infection is either the onset of probable or proven CMV end-organ disease or initiation of anti-CMV PET with approved anti-CMV agents (ganciclovir, valganciclovir, foscarnet, and/or cidofovir) based on documented CMV viremia and the clinical condition of the participant. Time to onset of clinically significant CMV infection is the elapsed time from transplant to the onset of CMV end-organ disease or to the initiation of anti-CMV PET. Time to onset was determined from the Kaplan-Meier method for censored data.

All randomized participants who received at least 1 dose of study intervention.

Posted

Median

95% Confidence Interval

Days

From Week 14 post-transplant to Week 28 post-transplant (approximately 14 weeks)

ID	Title	Description
OG000	Letermovir	Participants who received HSCT transplant and 100 days of LET prophylaxis were randomized to an additional 100 days of LET (480 mg once daily alone or 240 mg once daily for participants on cyclosporin A) treatment.
OG001	Placebo	Participants who received HSCT transplant and 100 days of LET prophylaxis were randomized to an additional 100 days of placebo treatment.

Secondary

Time to Onset of Clinically Significant CMV Infection From Week 14 Post-transplant to Week 48 Post-transplant

Clinically significant CMV infection is either the onset of probable or proven CMV end-organ disease or initiation of anti-CMV PET with approved anti-CMV agents (ganciclovir, valganciclovir, foscarnet, and/or cidofovir) based on documented CMV viremia and the clinical condition of the participant. Time to onset of clinically significant CMV infection is the elapsed time from transplant to the onset of CMV end-organ disease or to the initiation of anti-CMV PET. Time to onset was determined from the Kaplan-Meier method for censored data.

All randomized participants who received at least 1 dose of study intervention.

Posted

Median

95% Confidence Interval

Days

From Week 14 post-transplant to Week 48 post-transplant (approximately 34 weeks)

ID	Title	Description
OG000	Letermovir	Participants who received HSCT transplant and 100 days of LET prophylaxis were randomized to an additional 100 days of LET (480 mg once daily alone or 240 mg once daily for participants on cyclosporin A) treatment.
OG001	Placebo	Participants who received HSCT transplant and 100 days of LET prophylaxis were randomized to an additional 100 days of placebo treatment.

Secondary

Percentage of Participants With CMV Viremia Who Started PET From Week 14 Post-transplant to Week 28 Post-transplant

The percentage of participants with CMV viremia who initiated PET of anti-CMV agents (ganciclovir, valganciclovir, foscarnet, and/or cidofovir) was determined. Missing values were handled with the OF approach, where failure was defined as all participants who develop clinically significant CMV infection or discontinue prematurely from the study with CMV viremia from week 14 through week 28 post-transplant.

All randomized participants who received at least 1 dose of study intervention.

Posted

Number

Percentage of participants

From Week 14 post-transplant to Week 28 post-transplant (approximately 14 weeks)

ID	Title	Description
OG000	Letermovir	Participants who received HSCT transplant and 100 days of LET prophylaxis were randomized to an additional 100 days of LET (480 mg once daily alone or 240 mg once daily for participants on cyclosporin A) treatment.
OG001	Placebo	Participants who received HSCT transplant and 100 days of LET prophylaxis were randomized to an additional 100 days of placebo treatment.

Units	Counts

Secondary

Percentage of Participants With CMV Viremia Who Started PET From Week 14 Post-transplant to Week 48 Post-transplant

All randomized participants who received at least 1 dose of study intervention.

Posted

Number

Percentage of participants

From Week 14 post-transplant to Week 48 post-transplant (approximately 34 weeks)

ID	Title	Description
OG000	Letermovir	Participants who received HSCT transplant and 100 days of LET prophylaxis were randomized to an additional 100 days of LET (480 mg once daily alone or 240 mg once daily for participants on cyclosporin A) treatment.
OG001	Placebo	Participants who received HSCT transplant and 100 days of LET prophylaxis were randomized to an additional 100 days of placebo treatment.

Units	Counts

Secondary

Percentage of Participants With All-cause Mortality From Week 14 Post-transplant to Week 28 Post-transplant

The percentage of participants who died due to any cause (all-cause mortality) from Week 14 to Week 28 was determined.

All randomized participants who received at least 1 dose of study intervention.

Posted

Number

Percentage of participants

From Week 14 post-transplant to Week 28 post-transplant (approximately 14 weeks)

ID	Title	Description
OG000	Letermovir	Participants who received HSCT transplant and 100 days of LET prophylaxis were randomized to an additional 100 days of LET (480 mg once daily alone or 240 mg once daily for participants on cyclosporin A) treatment.
OG001	Placebo	Participants who received HSCT transplant and 100 days of LET prophylaxis were randomized to an additional 100 days of placebo treatment.

Units	Counts
Participants	OG000

Secondary

Percentage of Participants With All-cause Mortality From Week 14 Post-transplant to Week 48 Post-transplant

The percentage of participants who died due to any cause (all-cause mortality) from Week 14 to Week 48 was determined.

All randomized participants who received at least 1 dose of study intervention.

Posted

Number

Percentage of participants

From Week 14 post-transplant to Week 48 post-transplant (approximately 34 weeks)

ID	Title	Description
OG000	Letermovir	Participants who received HSCT transplant and 100 days of LET prophylaxis were randomized to an additional 100 days of LET (480 mg once daily alone or 240 mg once daily for participants on cyclosporin A) treatment.
OG001	Placebo	Participants who received HSCT transplant and 100 days of LET prophylaxis were randomized to an additional 100 days of placebo treatment.

Units	Counts
Participants	OG000

Secondary

Time to All-cause Mortality From Week 14 Post-transplant to Week 28 Post-transplant

Time to all-cause mortality is the time elapsed after Week 14 post-transplant and death due to any cause, and was determined from the Kaplan-Meier method for censored data.

All randomized participants who received at least 1 dose of study intervention.

Posted

Median

95% Confidence Interval

Days

From Week 14 post-transplant to Week 28 post-transplant (approximately 14 weeks)

ID	Title	Description
OG000	Letermovir	Participants who received HSCT transplant and 100 days of LET prophylaxis were randomized to an additional 100 days of LET (480 mg once daily alone or 240 mg once daily for participants on cyclosporin A) treatment.
OG001	Placebo	Participants who received HSCT transplant and 100 days of LET prophylaxis were randomized to an additional 100 days of placebo treatment.

Units	Counts
Participants	OG000

Secondary

Time to All-cause Mortality From Week 14 Post-transplant to Week 48 Post-transplant

Time to all-cause mortality is the time elapsed after Week 14 post-transplant and death due to any cause, and was determined from the Kaplan-Meier method for censored data.

All randomized participants who received at least 1 dose of study intervention.

Posted

Median

95% Confidence Interval

Days

From Week 14 post-transplant to Week 48 post-transplant (approximately 34 weeks)

ID	Title	Description
OG000	Letermovir	Participants who received HSCT transplant and 100 days of LET prophylaxis were randomized to an additional 100 days of LET (480 mg once daily alone or 240 mg once daily for participants on cyclosporin A) treatment.
OG001	Placebo	Participants who received HSCT transplant and 100 days of LET prophylaxis were randomized to an additional 100 days of placebo treatment.

Units	Counts
Participants	OG000

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected144 at risk EG0012 events1 affected74 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected144 at risk EG0011 events1 affected74 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected144 at risk EG0012 events2 affected74 at risk
Pure white cell aplasia	Blood and lymphatic system disorders	MedDRA 25.0	Systematic Assessment	EG0002 events1 affected144 at risk EG0010 events0 affected74 at risk
Thrombotic microangiopathy	Blood and lymphatic system disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected144 at risk EG0012 events2 affected74 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected74 at risk
Pericarditis	Cardiac disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected74 at risk
Aplasia	Congenital, familial and genetic disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected74 at risk
Thyroiditis subacute	Endocrine disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected74 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0002 events2 affected144 at risk EG0010 events0 affected74 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected74 at risk
Haematochezia	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected74 at risk
Intestinal perforation	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected74 at risk
Pneumatosis intestinalis	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected144 at risk EG0012 events1 affected74 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected74 at risk
Multiple organ dysfunction syndrome	General disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected74 at risk
Pyrexia	General disorders	MedDRA 25.0	Systematic Assessment	EG0004 events4 affected144 at risk EG0012 events1 affected74 at risk
Graft versus host disease	Immune system disorders	MedDRA 25.0	Systematic Assessment	EG0009 events9 affected144 at risk EG0016 events6 affected74 at risk
Acute sinusitis	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected144 at risk EG0011 events1 affected74 at risk
Adenoviral haemorrhagic cystitis	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected74 at risk
Adenovirus infection	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected74 at risk
Anal abscess	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected144 at risk EG0012 events2 affected74 at risk
Appendicitis	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected74 at risk
Bronchopulmonary aspergillosis	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected144 at risk EG0012 events2 affected74 at risk
COVID-19	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected74 at risk
COVID-19 pneumonia	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected144 at risk EG0014 events2 affected74 at risk
Cellulitis	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected74 at risk
Cerebral toxoplasmosis	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected74 at risk
Clostridium difficile colitis	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected74 at risk
Cytomegalovirus chorioretinitis	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected74 at risk
Cytomegalovirus infection	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected74 at risk
Cytomegalovirus infection reactivation	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected74 at risk
Cytomegalovirus viraemia	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected74 at risk
Escherichia infection	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected74 at risk
Gastroenteritis viral	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected74 at risk
Herpes simplex	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected74 at risk
Human herpesvirus 6 infection	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected74 at risk
Influenza	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected74 at risk
Lower respiratory tract infection fungal	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected74 at risk
Lymph node tuberculosis	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected74 at risk
Mastoiditis	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected74 at risk
Myelitis	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected74 at risk
Neutropenic sepsis	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected74 at risk
Pneumocystis jirovecii pneumonia	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected144 at risk EG0011 events1 affected74 at risk
Pneumonia	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0004 events4 affected144 at risk EG0015 events5 affected74 at risk
Pneumonia aspiration	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected74 at risk
Pneumonia bacterial	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0002 events2 affected144 at risk EG0010 events0 affected74 at risk
Pneumonia fungal	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected74 at risk
Pneumonia influenzal	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected74 at risk
Pneumonia klebsiella	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected74 at risk
Pneumonia pseudomonal	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected74 at risk
Pneumonia viral	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected144 at risk EG0011 events1 affected74 at risk
Pseudomonal sepsis	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected74 at risk
Rhinovirus infection	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected74 at risk
Sepsis	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0002 events2 affected144 at risk EG0012 events2 affected74 at risk
Septic shock	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected74 at risk
Staphylococcal infection	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected74 at risk
Urinary tract infection	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected74 at risk
Vascular device infection	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected144 at risk EG0012 events2 affected74 at risk
Viral upper respiratory tract infection	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected144 at risk EG0011 events1 affected74 at risk
Subdural haematoma	Injury, poisoning and procedural complications	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected74 at risk
Transplant failure	Injury, poisoning and procedural complications	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected74 at risk
Escherichia test positive	Investigations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected74 at risk
Platelet count decreased	Investigations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected74 at risk
Troponin increased	Investigations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected74 at risk
Hypoproteinaemia	Metabolism and nutrition disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected74 at risk
Pathological fracture	Musculoskeletal and connective tissue disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected74 at risk
Acute lymphocytic leukaemia recurrent	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.0	Systematic Assessment	EG0002 events2 affected144 at risk EG0010 events0 affected74 at risk
Acute myeloid leukaemia recurrent	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.0	Systematic Assessment	EG0008 events8 affected144 at risk EG0013 events3 affected74 at risk
Chloroma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected74 at risk
Large granular lymphocytosis	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected74 at risk
Lymphoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected74 at risk
Myelodysplastic syndrome	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected74 at risk
Peripheral T-cell lymphoma unspecified recurrent	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected74 at risk
Plasma cell myeloma recurrent	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected74 at risk
Post transplant lymphoproliferative disorder	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.0	Systematic Assessment	EG0003 events2 affected144 at risk EG0011 events1 affected74 at risk
Guillain-Barre syndrome	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected74 at risk
Confusional state	Psychiatric disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected74 at risk
Nephrolithiasis	Renal and urinary disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected74 at risk
Heavy menstrual bleeding	Reproductive system and breast disorders	MedDRA 25.0	Systematic Assessment	EG0002 events1 affected144 at risk EG0010 events0 affected74 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected74 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected74 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected74 at risk

ID	Term
D006566	Herpesviridae Infections
D004266	DNA Virus Infections
D014777	Virus Diseases
D007239	Infections

ID	Title	Description
BG000	Letermovir	Participants who received HSCT transplant and 100 days of LET prophylaxis were randomized to an additional 100 days of LET (480 mg once daily alone or 240 mg once daily for participants on cyclosporin A) treatment.
BG001	Placebo	Participants who received HSCT transplant and 100 days of LET prophylaxis were randomized to an additional 100 days of placebo treatment.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Letermovir	Participants who received HSCT transplant and 100 days of LET prophylaxis were randomized to an additional 100 days of LET (480 mg once daily alone or 240 mg once daily for participants on cyclosporin A) treatment.	16	145	49	144	100	144
EG001	Placebo	Participants who received HSCT transplant and 100 days of LET prophylaxis were randomized to an additional 100 days of placebo treatment.	8	75	27	74	58	74