Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43865   clinical trials with a EudraCT protocol, of which   7286   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A Phase 3, Multicenter, Randomized, Double blind, Double-dummy, Active-controlled Study to Assess the Efficacy and Safety of Maribavir Compared to Valganciclovir for the Treatment of Cytomegalovirus (CMV) Infection in Hematopoietic Stem Cell Transplant Recipients

    Summary
    EudraCT number
    		 2015-004726-34
    Trial protocol
    		 HU   DE   GB   ES   BE   CZ   PL   FR   HR   IT   GR   AT   Outside EU/EEA  
    Global end of trial date
    01 Jul 2022

    Results information
    Results version number
    		 v1(current)
    This version publication date
    04 Jan 2023
    First version publication date
    04 Jan 2023
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    SHP620-302
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02927067
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Shire
    Sponsor organisation address
    300 Shire Way, Lexington, MA, United States, 02421
    Public contact
    Study Director, Shire, ClinicalTransparency@shire.com
    Scientific contact
    Study Director, Shire, ClinicalTransparency@shire.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    		 EMEA-000353-PIP02-16
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    01 Jul 2022
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    01 Jul 2022
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The main objective of the study is to compare the efficacy of maribavir to valganciclovir in CMV viremia clearance at the end of Study Week 8 in asymptomatic CMV infection in Hematopoietic Stem Cell Transplant (HSCT) recipients.
    Protection of trial subjects
    All study participants were required to read and sign an Informed Consent Form.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    14 Apr 2017
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Australia: 32
    Country: Number of subjects enrolled
    China: 18
    Country: Number of subjects enrolled
    Korea, Republic of: 5
    Country: Number of subjects enrolled
    New Zealand: 17
    Country: Number of subjects enrolled
    Singapore: 18
    Country: Number of subjects enrolled
    Belgium: 61
    Country: Number of subjects enrolled
    Switzerland: 6
    Country: Number of subjects enrolled
    Czechia: 2
    Country: Number of subjects enrolled
    Germany: 20
    Country: Number of subjects enrolled
    Spain: 130
    Country: Number of subjects enrolled
    France: 48
    Country: Number of subjects enrolled
    United Kingdom: 28
    Country: Number of subjects enrolled
    Greece: 1
    Country: Number of subjects enrolled
    Croatia: 8
    Country: Number of subjects enrolled
    Hungary: 3
    Country: Number of subjects enrolled
    Israel: 4
    Country: Number of subjects enrolled
    Italy: 11
    Country: Number of subjects enrolled
    Poland: 3
    Country: Number of subjects enrolled
    Russian Federation: 1
    Country: Number of subjects enrolled
    Turkey: 11
    Country: Number of subjects enrolled
    Canada: 15
    Country: Number of subjects enrolled
    United States: 111
    Worldwide total number of subjects
    553
    EEA total number of subjects
    287
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    4
    Adults (18-64 years)
    421
    From 65 to 84 years
    128
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Participants were randomized at 97 sites in United States,Spain,France,Germany,United Kingdom,Belgium,China,Italy,Israel,Australia,Canada,Singapore,Croatia, Czech Republic,Greece,Hungary,Korea,New Zealand,Poland,Russia,Switzerland, and Turkey from 14 April 2017(first participant first visit) to 01 July 2022(last participant last visit).

    Pre-assignment
    Screening details
    		 Participants who were hematopoietic stem cell transplant (HSCT) recipients with a diagnosis of asymptomatic cytomegalovirus (CMV) infection were enrolled then randomized in a 1:1 ratio to receive either maribavir or valganciclovir (along with placebo matched to comparator) in each arm in a double-blind, double-dummy fashion.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Valganciclovir 900 mg BID
    Arm description
    		 Participants received 900 milligrams (mg) of valganciclovir along with a placebo matched to maribavir, twice daily (BID) orally for 8 weeks. Valganciclovir dose was allowed to be adjusted to 450 mg BID or 450 mg QD based on renal function impairment assessed at baseline or development of neutropenia during the study.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo tablets matched to maribavir.

    Investigational medicinal product name
    Valganciclovir
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Valganciclovir 900 mg, BID. Dose was adjusted to 450 mg BID or 450 mg QD during the study for renal function impairment or neutropenia.

    Arm title
    		 Maribavir 400 mg BID
    Arm description
    		 Participants received 400 mg of maribavir along with a placebo matched to valganciclovir, BID orally for 8 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo tablets matched to valganciclovir.

    Investigational medicinal product name
    Maribavir
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Maribavir 400 mg BID.

    Number of subjects in period 1
    		Valganciclovir 900 mg BID Maribavir 400 mg BID
    Started
    277
    276
    Treated Participants
    274
    273
    Participants Received 8 Weeks Treatment
    140 [1]
    179 [2]
    Completed
    217
    215
    Not completed
    60
    61
         Adverse event, serious fatal
    18
    31
         Adverse event, non-fatal
    13
    10
         Withdrawn Consent
    20
    12
         Reason not Specified
    4
    6
         Noncompliance
    5
    2
    Notes
    [1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Participants who received 8 weeks of treatment include the participants who completed study drug treatment.
    [2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Treated participants (full analysis set) included the participants from the randomized set who took at least one dose of assigned study drug and were analyzed for efficacy and safety evaluations.

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Valganciclovir 900 mg BID
    Reporting group description
    		 Participants received 900 milligrams (mg) of valganciclovir along with a placebo matched to maribavir, twice daily (BID) orally for 8 weeks. Valganciclovir dose was allowed to be adjusted to 450 mg BID or 450 mg QD based on renal function impairment assessed at baseline or development of neutropenia during the study.

    Reporting group title
    Maribavir 400 mg BID
    Reporting group description
    		 Participants received 400 mg of maribavir along with a placebo matched to valganciclovir, BID orally for 8 weeks.

    Reporting group values
    		 Valganciclovir 900 mg BID Maribavir 400 mg BID Total
    Number of subjects
    		 277 276
    Age Categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 51.8 ± 15.22 53.1 ± 13.96 -
    Gender categorical
    Units: Subjects
        Female
    		 110 126 236
        Male
    		 167 150 317
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 1 0 1
        Asian
    		 39 36 75
        Native Hawaiian or Other Pacific Islander
    		 3 0 3
        Black or African American
    		 9 10 19
        White
    		 200 221 421
        More than one race
    		 0 0 0
        Unknown or Not Reported
    		 25 9 34
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 37 35 72
        Not Hispanic or Latino
    		 193 216 409
        Unknown or Not Reported
    		 47 25 72
    Region of Enrollment
    Units: Subjects
        Australia Australia
    		 13 19 32
        China China
    		 9 9 18
        Korea, South Korea, Republic of
    		 3 2 5
        New Zealand New Zealand
    		 10 7 17
        Belgium Belgium
    		 31 30 61
        Switzerland Switzerland
    		 4 2 6
        Czech Republic Czechia
    		 0 2 2
        Germany Germany
    		 9 11 20
        Spain Spain
    		 61 69 130
        France France
    		 34 14 48
        United Kingdom United Kingdom
    		 14 14 28
        Greece Greece
    		 1 0 1
        Croatia Croatia
    		 4 4 8
        Hungary Hungary
    		 2 1 3
        Israel Israel
    		 2 2 4
        Italy Italy
    		 7 4 11
        Poland Poland
    		 1 2 3
        Russia Russia
    		 1 0 1
        Turkey Turkey
    		 6 5 11
        Canada Canada
    		 8 7 15
        United States United States
    		 50 61 111
        Singapore Singapore
    		 7 11 18
    Height
    Units: cm
        arithmetic mean (standard deviation)
    		 169.58 ± 9.391 168.75 ± 9.579 -
    Weight
    Units: kg
        arithmetic mean (standard deviation)
    		 70.31 ± 15.247 70.98 ± 16.779 -
    Body Mass Index (BMI)
    BMI = Body Mass Index. It is computed by [weight (kg) / height (cm)^2] x 10,000.
    Units: kg/m^2
        arithmetic mean (standard deviation)
    		 24.38 ± 4.628 24.90 ± 5.007 -

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Valganciclovir 900 mg BID
    Reporting group description
    		 Participants received 900 milligrams (mg) of valganciclovir along with a placebo matched to maribavir, twice daily (BID) orally for 8 weeks. Valganciclovir dose was allowed to be adjusted to 450 mg BID or 450 mg QD based on renal function impairment assessed at baseline or development of neutropenia during the study.

    Reporting group title
    Maribavir 400 mg BID
    Reporting group description
    		 Participants received 400 mg of maribavir along with a placebo matched to valganciclovir, BID orally for 8 weeks.

    Primary: Number of Participants Who Achieved Confirmed Clearance of Plasma Cytomegalovirus (CMV) Deoxyribose Nucleic Acid (DNA) at the end of Study Week 8

    		 Close Top of page
    End point title
    		 Number of Participants Who Achieved Confirmed Clearance of Plasma Cytomegalovirus (CMV) Deoxyribose Nucleic Acid (DNA) at the end of Study Week 8
    End point description
    Confirmed CMV viremia clearance is defined as plasma CMV DNA concentrations less than lower limit of quantification (LLOQ; i.e. <137 International units per milliliter [IU/mL]), when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV Test in 2 consecutive post baseline samples separated by at least 5 days. To be considered a responder for the primary endpoint, the participant must have received exclusively study-assigned treatment (regardless of whether study-assigned treatment was completed).
    End point type
    Primary
    End point timeframe
    Week 8
    End point values
    		 Valganciclovir 900 mg BID Maribavir 400 mg BID
    Number of subjects analysed
    274
    273
    Units: participants
    212
    190
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Maribavir 400 mg BID v Valganciclovir 900 mg BID
    Number of subjects included in analysis
    547
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [1]
    Method
    Parameter type
    		 Difference in Percentage of Responders
    Point estimate
    -7.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -14.98
         upper limit
    		 -0.36
    Notes
    [1] - The non-inferiority (NI) margin of the primary efficacy endpoint was 7%. If the lower limit of the 95% confidence interval (CI) was greater than -7%, then NI was assumed. Assuming 68% (maribavir) and 60% (valganciclovir) subjects achieve confirmed viremia clearance, 494 subjects (247 per group) will yield >90% power to declare NI based on 2-group test of equivalence in proportions (nQuery Advisor 7.0). Considering 10% dropout, 550 subjects (275 subjects per group) were enrolled and randomized.

    Secondary: Number of Participants who Achieved Confirmed CMV Viremia Clearance and CMV Infection Symptom Control at the end of Week 8, Followed by Maintenance of Treatment Effect at Week 16

    		 Close Top of page
    End point title
    		 Number of Participants who Achieved Confirmed CMV Viremia Clearance and CMV Infection Symptom Control at the end of Week 8, Followed by Maintenance of Treatment Effect at Week 16
    End point description
    Confirmed CMV viremia clearance is defined as plasma CMV DNA concentrations less than lower limit of quantification (LLOQ; i.e. <137 International units per milliliter [IU/mL]), when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV Test in 2 consecutive post baseline samples separated by at least 5 days. To be considered a responder for this key secondary endpoint, the participant must have received exclusively study-assigned treatment (regardless of whether study-assigned treatment was completed).
    End point type
    Secondary
    End point timeframe
    Week 8 up to Week 16
    End point values
    		 Valganciclovir 900 mg BID Maribavir 400 mg BID
    Number of subjects analysed
    274
    273
    Units: participants
    133
    144
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Valganciclovir 900 mg BID v Maribavir 400 mg BID
    Number of subjects included in analysis
    547
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [2]
    Method
    Parameter type
    		 Difference in Percentage of Responders
    Point estimate
    4.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.91
         upper limit
    		 12.76
    Notes
    [2] - The non-inferiority margin of the key secondary efficacy endpoint was 7%. If the lower limit of the 95% CI was greater than -7%, then noninferiority (NI) was assumed. Because the NI of the primary efficacy endpoint was not established, the NI hypothesis of the key secondary endpoint was not tested formally.

    Secondary: Number of Participants who Achieved Confirmed Clearance of Plasma CMV DNA (CMV Viremia Clearance) at Week 8 After Receiving 8 Weeks of Study Assigned Treatment

    		 Close Top of page
    End point title
    		 Number of Participants who Achieved Confirmed Clearance of Plasma CMV DNA (CMV Viremia Clearance) at Week 8 After Receiving 8 Weeks of Study Assigned Treatment
    End point description
    Confirmed CMV viremia clearance is defined as plasma CMV DNA concentrations less than lower limit of quantification (LLOQ; i.e. <137 International units per milliliter [IU/mL]), when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV Test in 2 consecutive post baseline samples separated by at least 5 days. To be considered a responder for this secondary endpoint, the participant must have received exclusively study-assigned treatment for 8 weeks. Participants who discontinued treatment early were non-responders for this endpoint.
    End point type
    Secondary
    End point timeframe
    Week 8
    End point values
    		 Valganciclovir 900 mg BID Maribavir 400 mg BID
    Number of subjects analysed
    274
    273
    Units: participants
    137
    158
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Valganciclovir 900 mg BID v Maribavir 400 mg BID
    Number of subjects included in analysis
    547
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.061 [3]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Difference in Percentage of Responders
    Point estimate
    8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.38
         upper limit
    		 16.3
    Notes
    [3] - The CMH weighted average approach (stratified for baseline plasma CMV DNA concentration and acute GVHD status) was used for the adjusted difference in percentage of responders (Maribavir−Valganciclovir), the corresponding 95% CI, and the p−value.

    Secondary: Number of Participants who Achieved Confirmed CMV Viremia Clearance After Receiving 8 Weeks of Study-assigned Treatment Through Weeks 12, 16 and 20

    		 Close Top of page
    End point title
    		 Number of Participants who Achieved Confirmed CMV Viremia Clearance After Receiving 8 Weeks of Study-assigned Treatment Through Weeks 12, 16 and 20
    End point description
    Confirmed CMV viremia clearance is defined as plasma CMV DNA concentrations less than lower limit of quantification (LLOQ; i.e. <137 International units per milliliter [IU/mL]), when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV Test in 2 consecutive post baseline samples separated by at least 5 days. To be considered a responder for this secondary endpoint, the participant must have received exclusively study-assigned treatment for 8 weeks.
    End point type
    Secondary
    End point timeframe
    Week 8 through Weeks 12, 16 and 20
    End point values
    		 Valganciclovir 900 mg BID Maribavir 400 mg BID
    Number of subjects analysed
    274
    273
    Units: participants
        Week 8
    137
    158
        Week 12
    98
    134
        Week 16
    82
    119
        Week 20
    72
    98
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Week 8
    Comparison groups
    Valganciclovir 900 mg BID v Maribavir 400 mg BID
    Number of subjects included in analysis
    547
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.061 [4]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Difference in Percentage of Responders
    Point estimate
    8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.38
         upper limit
    		 16.3
    Notes
    [4] - The CMH weighted average approach (stratified for baseline plasma CMV DNA concentration and acute GVHD status) was used for the adjusted difference in percentage of responders (Maribavir−Valganciclovir), the corresponding 95% CI, and the p−value.
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Week 12
    Comparison groups
    Valganciclovir 900 mg BID v Maribavir 400 mg BID
    Number of subjects included in analysis
    547
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.001 [5]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Difference in Percentage of Responders
    Point estimate
    13.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 5.23
         upper limit
    		 21.62
    Notes
    [5] - The CMH weighted average approach (stratified for baseline plasma CMV DNA concentration and acute GVHD status) was used for the adjusted difference in percentage of responders (Maribavir−Valganciclovir), the corresponding 95% CI, and the p−value.
    Statistical analysis title
    		 Statistical Analysis 3
    Statistical analysis description
    Week 16
    Comparison groups
    Valganciclovir 900 mg BID v Maribavir 400 mg BID
    Number of subjects included in analysis
    547
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [6]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Difference in Percentage of Responders
    Point estimate
    13.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 5.8
         upper limit
    		 21.87
    Notes
    [6] - The CMH weighted average approach (stratified for baseline plasma CMV DNA concentration and acute GVHD status) was used for the adjusted difference in percentage of responders (Maribavir−Valganciclovir), the corresponding 95% CI, and the p−value.
    Statistical analysis title
    		 Statistical Analysis 4
    Statistical analysis description
    Week 20
    Comparison groups
    Valganciclovir 900 mg BID v Maribavir 400 mg BID
    Number of subjects included in analysis
    547
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.014 [7]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Difference in Percentage of Responders
    Point estimate
    9.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.98
         upper limit
    		 17.5
    Notes
    [7] - The CMH weighted average approach (stratified for baseline plasma CMV DNA concentration and acute GVHD status) was used for the adjusted difference in percentage of responders (Maribavir−Valganciclovir), the corresponding 95% CI, and the p−value.

    Secondary: Number of Participants who Achieved Confirmed CMV Viremia Clearance and CMV Infection Symptom Control at Study Week 8 With Maintenance Through Weeks 12 and 20

    		 Close Top of page
    End point title
    		 Number of Participants who Achieved Confirmed CMV Viremia Clearance and CMV Infection Symptom Control at Study Week 8 With Maintenance Through Weeks 12 and 20
    End point description
    Confirmed CMV viremia clearance is defined as plasma CMV DNA concentrations less than lower limit of quantification (LLOQ; i.e. <137 International units per milliliter [IU/mL]), when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV Test in 2 consecutive post baseline samples separated by at least 5 days. To be considered a responder for this secondary endpoint, the participant must have received exclusively study-assigned treatment (regardless of whether study-assigned treatment was completed) and had no symptoms of tissue invasive CMV disease at Week 8, Week 8 through Week 12, and Week 8 through Week 20, respectively.
    End point type
    Secondary
    End point timeframe
    Week 8 through Weeks 12 and 20
    End point values
    		 Valganciclovir 900 mg BID Maribavir 400 mg BID
    Number of subjects analysed
    274
    273
    Units: participants
        Week 8
    211
    190
        Week 12
    157
    162
        Week 20
    116
    118
    Statistical analysis title
    		 Statisctical Analysis 1
    Statistical analysis description
    Week 8
    Comparison groups
    Valganciclovir 900 mg BID v Maribavir 400 mg BID
    Number of subjects included in analysis
    547
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.051 [8]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Difference in Percentage of Responders
    Point estimate
    -7.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -14.64
         upper limit
    		 0.02
    Notes
    [8] - The CMH weighted average approach (stratified for baseline plasma CMV DNA concentration and acute GVHD status) was used for the adjusted difference in percentage of responders (Maribavir−Valganciclovir), the corresponding 95% CI, and the p−value.
    Statistical analysis title
    		 Statistical Analysis 3
    Statistical analysis description
    Week 20
    Comparison groups
    Valganciclovir 900 mg BID v Maribavir 400 mg BID
    Number of subjects included in analysis
    547
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.809 [9]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Difference in Percentage of Responders
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.27
         upper limit
    		 9.31
    Notes
    [9] - The CMH weighted average approach (stratified for baseline plasma CMV DNA concentration and acute GVHD status) was used for the adjusted difference in percentage of responders (Maribavir−Valganciclovir), the corresponding 95% CI, and the p−value.
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Week 12
    Comparison groups
    Valganciclovir 900 mg BID v Maribavir 400 mg BID
    Number of subjects included in analysis
    547
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.606 [10]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Difference in Percentage of Responders
    Point estimate
    2.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.05
         upper limit
    		 10.37
    Notes
    [10] - The CMH weighted average approach (stratified for baseline plasma CMV DNA concentration and acute GVHD status) was used for the adjusted difference in percentage of responders (Maribavir−Valganciclovir), the corresponding 95% CI, and the p−value.

    Secondary: Number of Participants With Confirmed Recurrence of Viremia During First 8 Weeks of the Study

    		 Close Top of page
    End point title
    		 Number of Participants With Confirmed Recurrence of Viremia During First 8 Weeks of the Study
    End point description
    Recurrence of CMV viremia is defined as plasma CMV DNA concentration greater than or equal to (>=) LLOQ when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV Test in 2 consecutive plasma samples at least 5 days apart, after being unquantifiable (<LLOQ) for at least 5 days in 2 consecutive samples during the first 8 weeks of the study, during the 12 weeks of the follow up study phase, and at any time during the study.
    End point type
    Secondary
    End point timeframe
    Up to Week 8
    End point values
    		 Valganciclovir 900 mg BID Maribavir 400 mg BID
    Number of subjects analysed
    236
    226
    Units: participants
    6
    16
    No statistical analyses for this end point

    Secondary: Number of Participants With Confirmed Recurrence of Viremia During the Follow-up Period

    		 Close Top of page
    End point title
    		 Number of Participants With Confirmed Recurrence of Viremia During the Follow-up Period
    End point description
    Recurrence of CMV viremia is defined as plasma CMV DNA concentration greater than or equal to (>=) LLOQ when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV Test in 2 consecutive plasma samples at least 5 days apart, after being unquantifiable (<LLOQ) for at least 5 days in 2 consecutive samples during the first 8 weeks of the study, during the 12 weeks of the follow up study phase, and at any time during the study.
    End point type
    Secondary
    End point timeframe
    From Week 9 up to Week 20
    End point values
    		 Valganciclovir 900 mg BID Maribavir 400 mg BID
    Number of subjects analysed
    236
    226
    Units: participants
    47
    27
    No statistical analyses for this end point

    Secondary: Number of Participants With Confirmed Recurrence of Viremia While on Study Treatment and Off Treatment

    		Close Top of page
    End point title
    		 Number of Participants With Confirmed Recurrence of Viremia While on Study Treatment and Off Treatment
    End point description
    Recurrence of CMV viremia is defined as plasma CMV DNA concentration greater than or equal to (>=) LLOQ when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV Test in 2 consecutive plasma samples at least 5 days apart, after being unquantifiable (<LLOQ) for at least 5 days in 2 consecutive samples during the first 8 weeks of the study, during the 12 weeks of the follow up study phase, and at any time during the study.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 20
    End point values
    		 Valganciclovir 900 mg BID Maribavir 400 mg BID
    Number of subjects analysed
    236
    226
    Units: participants
        On Study
    0
    14
        Off Study
    53
    29
    No statistical analyses for this end point

    Secondary: Number of Participants With Confirmed Recurrence of Viremia at any Time During the Study

    		 Close Top of page
    End point title
    		 Number of Participants With Confirmed Recurrence of Viremia at any Time During the Study
    End point description
    Recurrence of CMV viremia is defined as plasma CMV DNA concentration greater than or equal to (>=) LLOQ when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV Test in 2 consecutive plasma samples at least 5 days apart, after being unquantifiable (<LLOQ) for at least 5 days in 2 consecutive samples during the first 8 weeks of the study, during the 12 weeks of the follow up study phase, and at any time during the study.
    End point type
    Secondary
    End point timeframe
    Up to Week 20
    End point values
    		 Valganciclovir 900 mg BID Maribavir 400 mg BID
    Number of subjects analysed
    236
    226
    Units: participants
    53
    43
    No statistical analyses for this end point

    Secondary: Incidence of Grade 3 or 4 (Shift from Baseline Grade <3) and Grade 4 Neutropenia (Shift from Baseline Grade <4) While on Study Treatment

    		 Close Top of page
    End point title
    		 Incidence of Grade 3 or 4 (Shift from Baseline Grade <3) and Grade 4 Neutropenia (Shift from Baseline Grade <4) While on Study Treatment
    End point description
    Grade 3 and grade 4 neutropenia are defined as absolute neutrophil count (ANC) <1000 per cubic millimeter (/mm^3) and ANC <500/mm^3 respectively. Incidence of Grade 3 or 4 neutropenia represents the percentage of participants with Grade <3 (or missing) neutropenia at baseline, but Grade 3 or 4 while on study treatment. Incidence of Grade 4 neutropenia represents the number of participants with Grade <4 (or missing) neutropenia at baseline, but Grade 4 while on study treatment.
    End point type
    Secondary
    End point timeframe
    From start of study drug to end of study drug + 1 day (up to approximately Week 8)
    End point values
    		 Valganciclovir 900 mg BID Maribavir 400 mg BID
    Number of subjects analysed
    274
    273
    Units: participants
        Grade 3 or Grade 4 Neutropenia
    137
    44
        Grade 4 Neutropenia
    61
    9
    No statistical analyses for this end point

    Secondary: Number of Participants With Treatment-Emergent Adverse Events During the on-Treatment Period

    		 Close Top of page
    End point title
    		 Number of Participants With Treatment-Emergent Adverse Events During the on-Treatment Period
    End point description
    An adverse event (AE) is any untoward medical occurrence in a clinical investigation participants administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE that has a start date on or after the first dose of study treatment, or that has a start date before the date of first dose of study treatment but increases in severity after the first dose of study treatment, will be considered a treatment-emergent AE (TEAE).
    End point type
    Secondary
    End point timeframe
    From the start of the study treatment to 7 days after the last dose of study treatment (up to approximately Week 9)
    End point values
    		 Valganciclovir 900 mg BID Maribavir 400 mg BID
    Number of subjects analysed
    274
    273
    Units: participants
    269
    268
    No statistical analyses for this end point

    Secondary: Predose Concentration (Cmin) of Maribavir

    		Close Top of page
    End point title
    		 Predose Concentration (Cmin) of Maribavir [11]
    End point description
    The primary plasma maribavir concentration dataset (primary concentration dataset) includes all plasma maribavir concentrations. Missing PK sampling times are imputed according to the sparse sampling schedule in primary concentration dataset.
    End point type
    Secondary
    End point timeframe
    Weeks 1, 4, and 8: pre-morning dose
    Notes
    [11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No statistical analysis was planned for this endpoint.
    End point values
    		 Maribavir 400 mg BID
    Number of subjects analysed
    225
    Units: micrograms per milliliter (µg/mL)
    arithmetic mean (standard deviation)
        Week 8 (n=225)
    9.17 ± 7.69
        Week 4 (n=190)
    8.71 ± 9.20
        Week 8 (n=164)
    7.02 ± 6.35
    No statistical analyses for this end point

    Secondary: Area Under the Concentration-Time Curve Over the 12-Hour Dosing Interval at Steady State AUC(0-tau) of Maribavir for Adolescent Participants Only

    		 Close Top of page
    End point title
    		 Area Under the Concentration-Time Curve Over the 12-Hour Dosing Interval at Steady State AUC(0-tau) of Maribavir for Adolescent Participants Only [12]
    End point description
    End point type
    Secondary
    End point timeframe
    Pre-morning dose, 1, 2, 3, 4, 6, 8, and 12 hours post-morning dose of Week 1
    Notes
    [12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No statistical analysis was planned for this endpoint.
    End point values
    		 Maribavir 400 mg BID
    Number of subjects analysed
    1
    Units: hours (h)*μg/mL
        arithmetic mean (full range (min-max))
    161 (161 to 161)
    No statistical analyses for this end point

    Secondary: Maximum Observed Plasma Concentration (Cmax) of Maribavir for Adolescent Participants Only

    		 Close Top of page
    End point title
    		 Maximum Observed Plasma Concentration (Cmax) of Maribavir for Adolescent Participants Only [13]
    End point description
    End point type
    Secondary
    End point timeframe
    Pre-morning dose, 1, 2, 3, 4, 6, 8, and 12 hours post-morning dose of Week 1
    Notes
    [13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No statistical analysis was planned for this endpoint.
    End point values
    		 Maribavir 400 mg BID
    Number of subjects analysed
    1
    Units: µg/mL
        arithmetic mean (full range (min-max))
    22.0 (22.0 to 22.0)
    No statistical analyses for this end point

    Secondary: Time When Maximum Concentration is Observed (Tmax) of Maribavir for Adolescent Participants Only

    		Close Top of page
    End point title
    		 Time When Maximum Concentration is Observed (Tmax) of Maribavir for Adolescent Participants Only [14]
    End point description
    End point type
    Secondary
    End point timeframe
    Pre-morning dose, 1, 2, 3, 4, 6, 8, and 12 hours post-morning dose of Week 1
    Notes
    [14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No statistical analysis was planned for this endpoint.
    End point values
    		 Maribavir 400 mg BID
    Number of subjects analysed
    1
    Units: hours (h)
        median (full range (min-max))
    0.92 (0.92 to 0.92)
    No statistical analyses for this end point

    Secondary: Apparent Oral Clearance (CL/F) of Maribavir for Adolescent Participants Only

    		 Close Top of page
    End point title
    		 Apparent Oral Clearance (CL/F) of Maribavir for Adolescent Participants Only [15]
    End point description
    End point type
    Secondary
    End point timeframe
    Pre-morning dose, 1, 2, 3, 4, 6, 8, and 12 hours post-morning dose of Week 1
    Notes
    [15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No statistical analysis was planned for this endpoint.
    End point values
    		 Maribavir 400 mg BID
    Number of subjects analysed
    1
    Units: liters per hour (L/h)
        arithmetic mean (full range (min-max))
    2.49 (2.49 to 2.49)
    No statistical analyses for this end point

    Secondary: Apparent Volume of Distribution (Vz/F) of Maribavir for Adolescent Participants Only

    		 Close Top of page
    End point title
    		 Apparent Volume of Distribution (Vz/F) of Maribavir for Adolescent Participants Only [16]
    End point description
    End point type
    Secondary
    End point timeframe
    Pre-morning dose, 1, 2, 3, 4, 6, 8, and 12 hours post-morning dose of Week 1
    Notes
    [16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No statistical analysis was planned for this endpoint.
    End point values
    		 Maribavir 400 mg BID
    Number of subjects analysed
    1
    Units: liters (L)
        arithmetic mean (full range (min-max))
    18.3 (18.3 to 18.3)
    No statistical analyses for this end point

    Other pre-specified: Percentage of Participants Developing Resistance

    		 Close Top of page
    End point title
    		 Percentage of Participants Developing Resistance
    End point description
    Resistance development was low in the two treatment arms and numerically higher in the maribavir arm. Percentages are rounded to one decimal place.
    End point type
    Other pre-specified
    End point timeframe
    From start of study drug up to end of the study (up to Week 20)
    End point values
    		 Valganciclovir 900 mg BID Maribavir 400 mg BID
    Number of subjects analysed
    274
    273
    Units: percentage of participants
        number (not applicable)
    2.9
    8.8
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    All-cause mortality: From start of study drug up to end of the study (up to Week 20); Serious and Other Adverse Events: From the start of the study drug to 7 days after the last dose of study treatment (up to approximately Week 9)
    Adverse event reporting additional description
    At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    23.0
    Reporting groups
    Reporting group title
    Maribavir 400 mg BID
    Reporting group description
    		 Participants received 400 mg of maribavir along with a placebo matched to valganciclovir, BID orally for 8 weeks.

    Reporting group title
    Valganciclovir 900 mg BID
    Reporting group description
    		 Participants received 900 mg of valganciclovir along with a placebo matched to maribavir, twice daily (BID) orally for 8 weeks. Valganciclovir dose was allowed to be adjusted to 450 mg BID or 450 mg QD based on renal function impairment assessed at baseline or development of neutropenia during the study.

    Serious adverse events
    		 Maribavir 400 mg BID Valganciclovir 900 mg BID
    Total subjects affected by serious adverse events
         subjects affected / exposed
    88 / 273 (32.23%)
    95 / 274 (34.67%)
         number of deaths (all causes)
    37
    29
         number of deaths resulting from adverse events
    18
    12
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acute lymphocytic leukaemia recurrent
         subjects affected / exposed
    0 / 273 (0.00%)
    2 / 274 (0.73%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute myeloid leukaemia
         subjects affected / exposed
    1 / 273 (0.37%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Acute myeloid leukaemia recurrent
         subjects affected / exposed
    2 / 273 (0.73%)
    2 / 274 (0.73%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 2
    0 / 2
    B precursor type acute leukaemia
         subjects affected / exposed
    1 / 273 (0.37%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diffuse large B-cell lymphoma
         subjects affected / exposed
    1 / 273 (0.37%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Leukaemic infiltration
         subjects affected / exposed
    0 / 273 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myelodysplastic syndrome
         subjects affected / exposed
    1 / 273 (0.37%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Lymphoma
         subjects affected / exposed
    1 / 273 (0.37%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Non-Hodgkin's lymphoma recurrent
         subjects affected / exposed
    1 / 273 (0.37%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transformation to acute myeloid leukaemia
         subjects affected / exposed
    0 / 273 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Hypotension
         subjects affected / exposed
    2 / 273 (0.73%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Shock
         subjects affected / exposed
    1 / 273 (0.37%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombophlebitis
         subjects affected / exposed
    1 / 273 (0.37%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Adverse drug reaction
         subjects affected / exposed
    1 / 273 (0.37%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    1 / 273 (0.37%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    1 / 273 (0.37%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    8 / 273 (2.93%)
    13 / 274 (4.74%)
         occurrences causally related to treatment / all
    0 / 9
    1 / 15
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Acute graft versus host disease in skin
         subjects affected / exposed
    4 / 273 (1.47%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute graft versus host disease in intestine
         subjects affected / exposed
    10 / 273 (3.66%)
    4 / 274 (1.46%)
         occurrences causally related to treatment / all
    0 / 11
    0 / 4
         deaths causally related to treatment / all
    0 / 6
    0 / 0
    Chronic graft versus host disease
         subjects affected / exposed
    0 / 273 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute graft versus host disease oral
         subjects affected / exposed
    1 / 273 (0.37%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic graft versus host disease in eye
         subjects affected / exposed
    1 / 273 (0.37%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic graft versus host disease in intestine
         subjects affected / exposed
    2 / 273 (0.73%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Haemophagocytic lymphohistiocytosis
         subjects affected / exposed
    1 / 273 (0.37%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transplant rejection
         subjects affected / exposed
    0 / 273 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Vulvovaginal pruritus
         subjects affected / exposed
    1 / 273 (0.37%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory distress syndrome
         subjects affected / exposed
    0 / 273 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cough
         subjects affected / exposed
    1 / 273 (0.37%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    3 / 273 (1.10%)
    2 / 274 (0.73%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary oedema
         subjects affected / exposed
    0 / 273 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    1 / 273 (0.37%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Mental status changes
         subjects affected / exposed
    0 / 273 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Platelet count decreased
         subjects affected / exposed
    1 / 273 (0.37%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic enzyme increased
         subjects affected / exposed
    1 / 273 (0.37%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Femur fracture
         subjects affected / exposed
    0 / 273 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infusion related reaction
         subjects affected / exposed
    0 / 273 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subdural haematoma
         subjects affected / exposed
    1 / 273 (0.37%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Product use issue
         subjects affected / exposed
    0 / 273 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subdural haemorrhage
         subjects affected / exposed
    1 / 273 (0.37%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Toxicity to various agents
         subjects affected / exposed
    0 / 273 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Angina pectoris
         subjects affected / exposed
    1 / 273 (0.37%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arrhythmia
         subjects affected / exposed
    0 / 273 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cardiac failure
         subjects affected / exposed
    1 / 273 (0.37%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiomyopathy
         subjects affected / exposed
    0 / 273 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pericardial effusion
         subjects affected / exposed
    0 / 273 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pericarditis
         subjects affected / exposed
    0 / 273 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Acute polyneuropathy
         subjects affected / exposed
    1 / 273 (0.37%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Autonomic nervous system imbalance
         subjects affected / exposed
    0 / 273 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Central nervous system lesion
         subjects affected / exposed
    1 / 273 (0.37%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral haemorrhage
         subjects affected / exposed
    0 / 273 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Dizziness
         subjects affected / exposed
    1 / 273 (0.37%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Limbic encephalitis
         subjects affected / exposed
    1 / 273 (0.37%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    0 / 273 (0.00%)
    3 / 274 (1.09%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Encephalopathy
         subjects affected / exposed
    2 / 273 (0.73%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nystagmus
         subjects affected / exposed
    1 / 273 (0.37%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Posterior reversible encephalopathy syndrome
         subjects affected / exposed
    1 / 273 (0.37%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    1 / 273 (0.37%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    3 / 273 (1.10%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tremor
         subjects affected / exposed
    1 / 273 (0.37%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Autoimmune haemolytic anaemia
         subjects affected / exposed
    1 / 273 (0.37%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anaemia
         subjects affected / exposed
    1 / 273 (0.37%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bone marrow failure
         subjects affected / exposed
    0 / 273 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    1 / 273 (0.37%)
    8 / 274 (2.92%)
         occurrences causally related to treatment / all
    1 / 1
    4 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    0 / 273 (0.00%)
    3 / 274 (1.09%)
         occurrences causally related to treatment / all
    0 / 0
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Leukopenia
         subjects affected / exposed
    0 / 273 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemolysis
         subjects affected / exposed
    1 / 273 (0.37%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancytopenia
         subjects affected / exposed
    2 / 273 (0.73%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    2 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    0 / 273 (0.00%)
    3 / 274 (1.09%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombotic microangiopathy
         subjects affected / exposed
    4 / 273 (1.47%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Warm type haemolytic anaemia
         subjects affected / exposed
    1 / 273 (0.37%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Neurosensory hypoacusis
         subjects affected / exposed
    0 / 273 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain lower
         subjects affected / exposed
    0 / 273 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    0 / 273 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    4 / 273 (1.47%)
    6 / 274 (2.19%)
         occurrences causally related to treatment / all
    0 / 4
    1 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dysbiosis
         subjects affected / exposed
    0 / 273 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 273 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematemesis
         subjects affected / exposed
    1 / 273 (0.37%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Melaena
         subjects affected / exposed
    1 / 273 (0.37%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    2 / 273 (0.73%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophagitis
         subjects affected / exposed
    1 / 273 (0.37%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 273 (0.37%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    2 / 273 (0.73%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    2 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis
         subjects affected / exposed
    0 / 273 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Drug-induced liver injury
         subjects affected / exposed
    1 / 273 (0.37%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    2 / 273 (0.73%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cystitis haemorrhagic
         subjects affected / exposed
    2 / 273 (0.73%)
    5 / 274 (1.82%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dysuria
         subjects affected / exposed
    1 / 273 (0.37%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal impairment
         subjects affected / exposed
    1 / 273 (0.37%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocrine disorders
    Adrenal insufficiency
         subjects affected / exposed
    0 / 273 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Bacteraemia
         subjects affected / exposed
    1 / 273 (0.37%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cystitis viral
         subjects affected / exposed
    0 / 273 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    0 / 273 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cytomegalovirus colitis
         subjects affected / exposed
    2 / 273 (0.73%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Cytomegalovirus enterocolitis
         subjects affected / exposed
    0 / 273 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cytomegalovirus gastritis
         subjects affected / exposed
    0 / 273 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cytomegalovirus gastroenteritis
         subjects affected / exposed
    0 / 273 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cytomegalovirus gastrointestinal infection
         subjects affected / exposed
    1 / 273 (0.37%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cytomegalovirus infection
         subjects affected / exposed
    3 / 273 (1.10%)
    3 / 274 (1.09%)
         occurrences causally related to treatment / all
    0 / 3
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cytomegalovirus infection reactivation
         subjects affected / exposed
    2 / 273 (0.73%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cytomegalovirus oesophagitis
         subjects affected / exposed
    1 / 273 (0.37%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cytomegalovirus viraemia
         subjects affected / exposed
    1 / 273 (0.37%)
    4 / 274 (1.46%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device related infection
         subjects affected / exposed
    1 / 273 (0.37%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device related sepsis
         subjects affected / exposed
    1 / 273 (0.37%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Disseminated toxoplasmosis
         subjects affected / exposed
    1 / 273 (0.37%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Epstein-Barr viraemia
         subjects affected / exposed
    1 / 273 (0.37%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epstein-Barr virus infection
         subjects affected / exposed
    2 / 273 (0.73%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Eye infection toxoplasmal
         subjects affected / exposed
    1 / 273 (0.37%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fournier's gangrene
         subjects affected / exposed
    0 / 273 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Fungal infection
         subjects affected / exposed
    0 / 273 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fungal sepsis
         subjects affected / exposed
    0 / 273 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Gastroenteritis
         subjects affected / exposed
    0 / 273 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis astroviral
         subjects affected / exposed
    1 / 273 (0.37%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis viral
         subjects affected / exposed
    1 / 273 (0.37%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Herpes zoster
         subjects affected / exposed
    1 / 273 (0.37%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Herpes zoster disseminated
         subjects affected / exposed
    1 / 273 (0.37%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Herpes zoster meningoencephalitis
         subjects affected / exposed
    2 / 273 (0.73%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Herpes zoster reactivation
         subjects affected / exposed
    1 / 273 (0.37%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    0 / 273 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Klebsiella bacteraemia
         subjects affected / exposed
    1 / 273 (0.37%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower respiratory tract infection bacterial
         subjects affected / exposed
    0 / 273 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower respiratory tract infection fungal
         subjects affected / exposed
    0 / 273 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Nasopharyngitis
         subjects affected / exposed
    0 / 273 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutropenic sepsis
         subjects affected / exposed
    0 / 273 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oral herpes
         subjects affected / exposed
    1 / 273 (0.37%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Parainfluenzae virus infection
         subjects affected / exposed
    1 / 273 (0.37%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    3 / 273 (1.10%)
    3 / 274 (1.09%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Pneumonia cytomegaloviral
         subjects affected / exposed
    1 / 273 (0.37%)
    2 / 274 (0.73%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pneumonia parainfluenzae viral
         subjects affected / exposed
    1 / 273 (0.37%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    1 / 273 (0.37%)
    2 / 274 (0.73%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    1 / 273 (0.37%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pseudomonal sepsis
         subjects affected / exposed
    0 / 273 (0.00%)
    2 / 274 (0.73%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rhinovirus infection
         subjects affected / exposed
    0 / 273 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 273 (0.37%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Streptococcal infection
         subjects affected / exposed
    1 / 273 (0.37%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    3 / 273 (1.10%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 3
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 273 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Toxoplasmosis
         subjects affected / exposed
    1 / 273 (0.37%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Varicella zoster virus infection
         subjects affected / exposed
    1 / 273 (0.37%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Viral infection
         subjects affected / exposed
    2 / 273 (0.73%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular device infection
         subjects affected / exposed
    1 / 273 (0.37%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Failure to thrive
         subjects affected / exposed
    1 / 273 (0.37%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Food intolerance
         subjects affected / exposed
    1 / 273 (0.37%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    1 / 273 (0.37%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    1 / 273 (0.37%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Maribavir 400 mg BID Valganciclovir 900 mg BID
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    245 / 273 (89.74%)
    256 / 274 (93.43%)
    Investigations
    Blood creatinine increased
         subjects affected / exposed
    18 / 273 (6.59%)
    12 / 274 (4.38%)
         occurrences all number
    18
    13
    Neutrophil count decreased
         subjects affected / exposed
    13 / 273 (4.76%)
    29 / 274 (10.58%)
         occurrences all number
    28
    52
    White blood cell count decreased
         subjects affected / exposed
    3 / 273 (1.10%)
    14 / 274 (5.11%)
         occurrences all number
    4
    15
    Platelet count decreased
         subjects affected / exposed
    17 / 273 (6.23%)
    16 / 274 (5.84%)
         occurrences all number
    21
    19
    Vascular disorders
    Hypertension
         subjects affected / exposed
    14 / 273 (5.13%)
    17 / 274 (6.20%)
         occurrences all number
    15
    19
    Nervous system disorders
    Headache
         subjects affected / exposed
    30 / 273 (10.99%)
    14 / 274 (5.11%)
         occurrences all number
    31
    16
    Dysgeusia
         subjects affected / exposed
    47 / 273 (17.22%)
    16 / 274 (5.84%)
         occurrences all number
    51
    17
    Taste disorder
         subjects affected / exposed
    23 / 273 (8.42%)
    6 / 274 (2.19%)
         occurrences all number
    24
    6
    Tremor
         subjects affected / exposed
    10 / 273 (3.66%)
    15 / 274 (5.47%)
         occurrences all number
    13
    16
    Blood and lymphatic system disorders
    Leukopenia
         subjects affected / exposed
    7 / 273 (2.56%)
    27 / 274 (9.85%)
         occurrences all number
    10
    37
    Anaemia
         subjects affected / exposed
    62 / 273 (22.71%)
    49 / 274 (17.88%)
         occurrences all number
    89
    57
    Thrombocytopenia
         subjects affected / exposed
    31 / 273 (11.36%)
    62 / 274 (22.63%)
         occurrences all number
    32
    79
    Neutropenia
         subjects affected / exposed
    44 / 273 (16.12%)
    144 / 274 (52.55%)
         occurrences all number
    60
    247
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    13 / 273 (4.76%)
    19 / 274 (6.93%)
         occurrences all number
    14
    22
    Fatigue
         subjects affected / exposed
    13 / 273 (4.76%)
    19 / 274 (6.93%)
         occurrences all number
    13
    20
    Oedema peripheral
         subjects affected / exposed
    27 / 273 (9.89%)
    26 / 274 (9.49%)
         occurrences all number
    29
    27
    Pyrexia
         subjects affected / exposed
    24 / 273 (8.79%)
    25 / 274 (9.12%)
         occurrences all number
    29
    29
    Immune system disorders
    Acute graft versus host disease in skin
         subjects affected / exposed
    46 / 273 (16.85%)
    32 / 274 (11.68%)
         occurrences all number
    55
    35
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    14 / 273 (5.13%)
    19 / 274 (6.93%)
         occurrences all number
    16
    22
    Constipation
         subjects affected / exposed
    16 / 273 (5.86%)
    10 / 274 (3.65%)
         occurrences all number
    17
    11
    Diarrhoea
         subjects affected / exposed
    50 / 273 (18.32%)
    44 / 274 (16.06%)
         occurrences all number
    67
    55
    Nausea
         subjects affected / exposed
    74 / 273 (27.11%)
    64 / 274 (23.36%)
         occurrences all number
    89
    79
    Vomiting
         subjects affected / exposed
    55 / 273 (20.15%)
    47 / 274 (17.15%)
         occurrences all number
    70
    59
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    20 / 273 (7.33%)
    26 / 274 (9.49%)
         occurrences all number
    20
    28
    Dyspnoea
         subjects affected / exposed
    2 / 273 (0.73%)
    14 / 274 (5.11%)
         occurrences all number
    2
    16
    Skin and subcutaneous tissue disorders
    Pruritus
         subjects affected / exposed
    10 / 273 (3.66%)
    17 / 274 (6.20%)
         occurrences all number
    10
    19
    Renal and urinary disorders
    Renal impairment
         subjects affected / exposed
    24 / 273 (8.79%)
    15 / 274 (5.47%)
         occurrences all number
    27
    19
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    18 / 273 (6.59%)
    16 / 274 (5.84%)
         occurrences all number
    19
    16
    Hypokalaemia
         subjects affected / exposed
    23 / 273 (8.42%)
    22 / 274 (8.03%)
         occurrences all number
    28
    23

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    01 Mar 2017
    -Modification of primary, key secondary, and secondary objectives to include participants who discontinue study treatment early and meet the criteria of confirmed CMV viremia clearance as responders in the primary efficacy analysis. -Modified Inclusion Criterion 5 to indicate that the current CMV infection must be the first episode of CMV viremia after HSCT, either primary or reactivation. -Clarified Inclusion Criterion 8 to indicate that urine pregnancy tests may be done per institutional requirements in addition to serum; however, they are not sufficient for eligibility determination. -Added a new Exclusion Criterion 3 to exclude participants with recurrent CMV infection. -Amended Exclusion Criterion 6 to indicate that participants must not be on treatment with anti-CMV agents (ganciclovir, valganciclovir, foscarnet or cidofovir) for the current CMV infection for longer than 72 hours. -Clarified in Exclusion Criterion 13 that subjects who have received an unapproved agent or device within 30 days before initiation of study treatment were not eligible. -Clarified Exclusion Criterion 16 indicating that known (previously documented) HIV historical results were accepted and no additional study testing was required. -Added an intensive PK sampling schedule for adolescents. -An additional pregnancy test at 4 weeks (Visit 6/Week 4) to obtain a monthly testing interval. -Addition of highly effective method of female and male contraception per the recommendations related to contraception and pregnancy testing in clinical trials by clinical trial facilitation group. -Addition recommendation for careful monitoring of concentration levels of concomitant medications that are substrates of CYP2C19 and P-gp both after initiation of maribavir (when substrate levels may increase) and after discontinuation of maribavir (when substrate levels may decrease), in alignment with the guidance to the investigators provided in the maribavir investigator’s brochure.
    01 Jun 2017
    - Added “CMV CNS infection” as one of the reasons for discontinuation and/or withdrawal. -Added basic descriptive statistics generally for all endpoints. -Added sensitivity analysis for investigation of homogeneity of treatment effect across centers/regions. -Added rules for conducting the interim population PK analysis.
    01 Sep 2017
    -Revised storage conditions of investigational product.
    04 Feb 2019
    -Expanded eligibility criteria for viral load and creatinine clearance (CrCl). -Added a third viral-load stratum for participants with very low viral load and high-risk infection, in addition to the existing low viral-load and high viral-load strata. -Added a study visit at Study Day 4 (±1) for participants taking a narrow therapeutic index immunosuppressive agent at baseline. -Added a visit 4 days after starting new therapy with a narrow therapeutic index immunosuppressive agent for participants who begin new therapy during the course of the treatment period to align the protocol with a recent recommendation from the DMC for Study SHP620-303. -Updated contact list, including removal of contacts for sites in Latin America. -Updated safety reporting contacts to a single Global Safety e-mail and fax contact per revised safety reporting procedures. -Added exclusion for concomitant letermovir and specified required washout period. -Clarified end of period for collecting nonserious AEs as up to 30 days after the last dose of study medication. -Modified the definition of overall study AEs to include events during the overall study period through the end of study, regardless of initiation of alternative anti-CMV treatment. -Modified criteria for reporting of CMV as an AE or SAE to harmonize with the reporting format used in Study SHP620-303. -Updated Table 12 Assessments of Responders for Key Secondary Endpoint (confirmed CMV viremia clearance at the end of Study Week 8 through Week 16) to ensure assessment of responder rates consistent with assessment specified in Study SHP620-303. -Eliminated the Hematopoietic Cell Transplant Comorbidity Index (HCT-CI) assessment and deleted Appendix 5 containing the index. -Clarified language regarding starting dosage regimens, as updated entry criteria require expansion of starting doses. -Added Graft Versus Host Disease (GVHD) assessment criteria forms and added tables for GVHD diagnosis criteria.
    11 Feb 2020
    -Added Modified Randomized Set, consisting of all participants in Randomized Set who take at least 1 dose of assigned study treatment. -Revised the exploratory efficacy endpoint of duration between the first confirmed CMV viremia clearance to viremia recurrence in all participants within 8 weeks of the study and through the end of study to time from the CMV viremia clearance at Week 8 to CMV viremia recurrence requiring alternative treatment. -Updated comorbidity status evaluation. -To align with the investigator’s brochure, updated the Cmax and AUC values for the increased tacrolimus when concomitantly administered with maribavir and changed 2D6 substrate to CYP2C19 substrate. -Updated number of completed for Phase 1 studies. -Removed references to an electronic diary (e-diary) due to the introduction of paper back-up diaries. -Updated the versions of the Valcyte Prescribing Information and Summary of Product Characteristics (SmPC) to specify the current version as documented in the Study Pharmacy Manual. -Corrected the unit of measure for hemoglobin. -Clarified that timing of comorbidity status evaluation is at Visit 6/Week 4 and Visit 10/Week 8. -Clarified follow-up to closure of unresolved SAEs rather than AEs at end of study. -Corrected pregnancy reporting information to indicate that it is the investigator’s responsibility to obtain pregnancy outcome/infant condition information within approximately 30 calendar days and 1 year postpartum. Removed requirement for a copy of the Investigational and Marketed Products Pregnancy Report Form being sent to the CRO/ sponsor medical monitor using details specified in the emergency contact information section of protocol. -Corrected information regarding reporting of SAEs. -Removed CIs from 3 secondary efficacy endpoints as they are not clinically meaningful for these analyses.
    06 Dec 2020
    -The protocol was amended to maintain participants safety, confidentiality, and study integrity in the context of healthcare delivery challenges presented by the COVID-19 pandemic. Amendment 6 provided flexibility to subjects to opt for home healthcare solutions as permitted by local regulations. This “hybrid study design” would offer subjects the option of in clinic or home healthcare for all study visits in the treatment phase. -Guidance was provided regarding changes to the study procedures that could be implemented for subjects or study sites affected by the COVID 19 Public Health Emergency. The guidance took references from the Food and Drug Administration Guidance on Conduct of Clinical Trials of Medical Products during COVID-19 Public Health Emergency - Guidance for Industry, Investigators, and Institutional Review Boards, March 2020, updated 03 June 2020, and the European Medicines Agency (EMA) Guidance on the Management of Clinical Trials During the COVID 19 (Coronavirus) Pandemic, Version 3 (28 Apr 2020).
    24 Mar 2021
    -Removed language extending measures to other situations beyond the COVID-19 pandemic (“or other future similar unexpected public health concerns” as this section applies only to the current COVID 19 pandemic. -Updated the guidance on management of clinical trials during the COVID 19 pandemic. Clarified that the site must contact the sponsor for approval of the alternative method for obtaining informed consent prior to implementation. -Clarified the recording of abuse, misuse, overdose, and medication errors on the AE CRF.
    02 Jul 2021
    The main purpose of Amendment 8 was to update the sponsor name and address from Shire ViroPharma, Inc (Shire) to Takeda Development Center Americas, Inc (TDC Americas; Takeda) and to clarify the secondary endpoints.
    15 Sep 2021
    The main purpose of Amendment 9 was to update description of drug interactions consistent with the latest Investigator’s Brochure.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Mon Apr 29 02:08:57 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA