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CompletedNCT02927067Updated Mar 3, 2023Results posted

A Study of Maribavir Compared to Valganciclovir to Treat Cytomegalovirus Infections in People Who Have Received Stem Cell Transplants

A Phase 3 interventional study of Maribavir and Valganciclovir in Cytomegalovirus (CMV), sponsored by Shire. Completed at 129 sites in 23 countries. Open to participants aged 16 Years and older. Per ClinicalTrials.gov, last updated 2023-03-03.

Sponsored by Shire · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
553
Allocation
Randomized
Ages
16 Years and older
Sex
All
01

Study summary

This study is about treatment options for cytomegalovirus infections in people who have received stem cell transplants. The main aim of the study is to check if the cytomegalovirus infection can no longer be detected after treatment with marivabir or valganciclovir.

Participants will take 2 tablets of marivabir or valganciclovir and 2 tablets of placebo twice a day for 8 weeks. A placebo will look like marivabir or valganciclovir but will not have any medicine in it.

After treatment, each participant will be followed up for up to 12 weeks.

Participants will visit their study clinic up to 18 times during the study.

02

Conditions studied

  • Cytomegalovirus (CMV)
03

In context

Cytomegalovirus Infections

359 studies on the registry are indexed under Cytomegalovirus Infections; 59 are open to participants now.

This study's enrollment of 553 is above the median of 60 across 233 interventional studies indexed under Cytomegalovirus Infections.

Browse Cytomegalovirus Infections studies →

Lead sponsor

Shire is the lead sponsor of 346 studies on the registry; 2 are open to participants now.

Of its 47 completed or terminated interventional studies of FDA-regulated products, 47 (100%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
16 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Be able to provide written, personally signed, and dated informed consent to participate in the study before completing any study-related procedures. As applicable, a parent/both parents or legally authorized representative (LAR) must provide signature of informed consent and there must be documentation of assent by the participants before completing any study-related procedures. During the COVID-19 public health emergency, informed consent from a potential or current trial participant may, if permitted by local laws and regulations, be obtained via electronic informed consent (eIC) capabilities or an electronic face-to-face consent interview when these individuals are unable to travel to the site (FDA COVID-19 Guidance, 27 January 2021, Q11).
  • Be greater than or equal to (>=) 16 years of age at the time of consent.
  • Be a recipient of hematopoietic stem cell transplant.

  • Have a documented asymptomatic CMV infection, with a screening value of CMV DNA >=1365 International Units per millilitre (IU/mL) to less than or equal to (\<=) 273000 IU/mL in whole blood or >=455 IU/mL to \<=91000 IU/mL in plasma in 2 consecutive assessments, separated by at least 1 day, as determined by local or central specialty laboratory quantitative polymerase chain reaction (qPCR) or comparable quantitative CMV DNA results. Both samples should be taken within 14 days prior to randomization with second sample obtained within 5 days prior to randomization. Same laboratory and same sample type (whole blood or plasma) should be used for these assessments. Asymptomatic CMV infection is defined as an infection that does not present with tissue invasive CMV disease, as assessed by the investigator. Participants with CMV DNA less than (\<) 910 and >=455 IU/mL in plasma or \<2730 and >=1365 IU/mL in whole blood will also need to meet at least 1 of the following criteria for high-risk CMV infection to be eligible:

    1. Human leukocyte antigen (HLA)-related (sibling) donor with at least 1 mismatch at 1 of the following 3 HLA-gene loci: HLA-A, -B or -DR,
    2. Haploidentical donor
    3. Unrelated donor with at least 1 mismatch at 1 of the following 4 HLA -gene loci: HLA-A, -B, -C and -DRB1,
    4. Use of umbilical cord blood as stem cell source,
    5. Use of ex vivo T-cell-depleted grafts,
    6. Grade 2 or greater graft-versus-host-disease (GVHD), requiring the use of systemic corticosteroids (defined as the use of >=1 milligram per kilogram per day (mg/kg/day) of prednisone or equivalent dose of another corticosteroid).
  • Have the current CMV infection as the first episode of CMV viremia after HSCT, either primary or reactivation, which in the investigator's opinion requires treatment.
  • Per investigator's judgment, be eligible for treatment with valganciclovir.

  • Have all of the following results as part of screening laboratory assessments (results from either the central laboratory or a local laboratory can be used for qualification):

    1. Absolute neutrophil count to >=1000 per cubic millimeter (/mm\^3) [1.0*10\^9/L].
    2. Platelet count >=25,000/mm\^3 [25*10\^9/L].
    3. Hemoglobin >=8 grams per deciliter (g/dL).
    4. Estimated creatinine clearance >=30 milliliters per minute (mL/min).
  • Have a negative serum beta human chorionic gonadotropin (beta-HCG) pregnancy test at screening, if a female of child bearing potential. Urine pregnancy tests may be done per institutional requirements; however they are not sufficient for eligibility determination. Sexually active females of child bearing potential must agree to comply with any applicable contraceptive requirements of the protocol. If male, must agree to use an acceptable method of birth control, as defined in the protocol, during the study treatment administration period and for 90 days afterward the last dose of study treatment.
  • Be able to swallow tablets.
  • Have life expectancy of >=8 weeks.
  • Weigh >=40 kilograms (kg).
  • Be willing and have an understanding and ability to fully comply with study procedures and restrictions defined in the protocol.

Exclusion criteria

Exclusion Criteria:

  • Have CMV tissue invasive disease as assessed by the investigator at the time of screening and randomization at Visit 2/Day 0.
  • Have a CMV infection that is known to be genotypically resistant to ganciclovir, valganciclovir, foscarnet, or cidofovir based on documented evidence.
  • Be presenting with recurrent CMV infection (defined as a new detection of CMV infection in a participants who had at least one previously documented episode of CMV infection post-transplant, and who has had at least 2 weeks of undetectable CMV DNA between the episodes during active surveillance, based on same local laboratory and same sample type). The Participants must also have been off any anti-CMV treatment between the current and prior infection. Otherwise, the current infection may be considered continuation of the prior infection.
  • Require ganciclovir, valganciclovir, foscarnet, or cidofovir administration for conditions other than CMV when study treatment is initiated (example: herpes simplex virus [HSV] co-infection requiring use of any of these agents after the randomization) or would need a co-administration with maribavir for CMV infection.
  • Be receiving leflunomide, letermovir, or artesunate when study treatment is initiated.

Note: Participants who may be receiving leflunomide must discontinue the use at least 14 days prior to randomization at Visit 2/Day 0 and the first dose of study treatment. Participants receiving letermovir must discontinue use 3 days prior to first dose of study treatment. Participants receiving artesunate must discontinue the use prior to the first dose of study treatment.

  • Be on treatment with anti-CMV agents (ganciclovir, valganciclovir, foscarnet or letermovir) for the current CMV infection for longer than 72 hours.
  • Have known hypersensitivity to the active substance or to an excipient of the study treatments.
  • Have severe vomiting, diarrhea, or other severe gastrointestinal illness within 24 hours prior to the first dose of study treatment that would preclude administration of oral medication.
  • Require mechanical ventilation or vasopressors for hemodynamic support at the time of randomization.
  • Be female and pregnant or nursing.
  • Have previously completed, discontinued, or have been withdrawn from this study.
  • Have received any investigational agent with known anti-CMV activity within 30 days before initiation of study treatment or CMV vaccine at any time.
  • Have received any unapproved agent or device within 30 days before initiation of study treatment.
  • Have any clinically significant medical or surgical condition that, in the investigator's opinion, could interfere with interpretation of study results, contraindicate the administration of the assigned study treatment, or compromise the safety or well-being of the participant.
  • Have previously received maribavir.
  • Have serum aspartate aminotransferase (AST) greater than (>) 5 times upper limit of normal (ULN) at screening, or serum alanine aminotransferase (ALT) >5 times ULN at screening, or total bilirubin >= 3.0*ULN at screening (except for documented Gilbert's syndrome), as analyzed by local or central laboratory.
  • Have known (previously documented) positive results for human immunodeficiency virus (HIV). Participants must have a confirmed negative HIV test result within 3 months of study entry or, if unavailable, be tested by a local laboratory during the screening period.
  • Have active malignancy with the exception of nonmelanoma skin cancer, as determined by the investigator. Participants who experience relapse or progression of their underlying malignancy (for which HSCT was performed), as determined by the investigator, are not to be enrolled.
  • Be undergoing treatment for acute or chronic hepatitis C
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
553 participants (actual)

Study arms

  • Active comparator
    Valganciclovir 900 mg BID

    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.

    Drug: Valganciclovir · Other: Placebo

  • Experimental
    Maribavir 400 mg BID

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

    Drug: Maribavir · Other: Placebo

Interventions

  • DrugMaribavir

    Participants will receive 400 mg of maribavir BID orally.

  • DrugValganciclovir

    Participants will receive valganciclovir tablets orally.

  • OtherPlacebo

    Participants will receive placebo tablets matched to either maribavir or valganciclovir.

06

What researchers measure

Primary outcomes

  1. Number of Participants Who Achieved Confirmed Clearance of Plasma Cytomegalovirus (CMV) Deoxyribose Nucleic Acid (DNA) at the End of Study Week 8

    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).

    Time frame: Week 8

Secondary outcomes

  1. 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

    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). CMV Infection Symptom Control is defined as no new clinical findings of CMV tissue invasive disease. Maintenance of Treatment Effect is defined as maintaining confirmed CMV viremia clearance and CMV infection symptom control through Week 16.

    Time frame: Week 8 up to Week 16

  2. 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

    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.

    Time frame: Week 8

  3. Number of Participants Who Achieved Confirmed CMV Viremia Clearance After Receiving 8 Weeks of Study-assigned Treatment Through Weeks 12, 16 and 20

    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.

    Time frame: Week 8 through Weeks 12, 16 and 20

  4. Number of Participants Who Maintained Confirmed CMV Viremia Clearance at Week 8 After Receiving Study-Assigned Treatment Through Study Weeks 12 and 20 Regardless of Whether Study Assigned Treatment Was Completed

    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 the 8-week study-assigned treatment was completed or discontinued early) and had no symptoms of tissue invasive CMV disease at Week 8, Week 8 through Week 12, and Week 8 through Week 20, respectively.

    Time frame: Week 8 through Weeks 12 and 20

  5. Number of Participants With Confirmed Recurrence of Viremia During First 8 Weeks of the Study

    Recurrence of CMV viremia is defined as plasma CMV DNA concentration greater than or equal to (\>=) 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 plasma samples at least 5 days apart, after being unquantifiable (\<LLOQ, i.e. \<137 IU/mL) 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.

    Time frame: Up to Week 8

  6. Number of Participants With Confirmed Recurrence of Viremia During the Follow-up Period

    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.

    Time frame: From Week 9 up to Week 20

  7. Number of Participants With Confirmed Recurrence of Viremia at Any Time During the Study

    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.

    Time frame: Up to Week 20

  8. Number of Participants With Confirmed Recurrence of Viremia While on Study Treatment and Off Treatment

    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.

    Time frame: Baseline up to Week 20

  9. Number of Participants With Grade 3 or 4 (Shift From Baseline Grade <3) and Grade 4 Neutropenia (Shift From Baseline Grade <4) While on Study Treatment

    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.

    Time frame: From start of study drug to end of study drug + 1 day (up to approximately Week 8)

  10. Number of Participants With Treatment-Emergent Adverse Events During the On-Treatment Period

    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).

    Time frame: From the start of the study treatment to 7 days after the last dose of study treatment (up to approximately Week 9)

  11. Predose Concentration (Cmin) of Maribavir

    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.

    Time frame: Weeks 1, 4, and 8: pre-morning dose

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

    Time frame: Pre-morning dose, 1, 2, 3, 4, 6, 8, and 12 hours post-morning dose of Week 1

  13. Maximum Observed Plasma Concentration (Cmax) of Maribavir for Adolescent Participants Only

    Time frame: Pre-morning dose, 1, 2, 3, 4, 6, 8, and 12 hours post-morning dose of Week 1

  14. Time When Maximum Concentration is Observed (Tmax) of Maribavir for Adolescent Participants Only

    Time frame: Pre-morning dose, 1, 2, 3, 4, 6, 8, and 12 hours post-morning dose of Week 1

  15. Apparent Oral Clearance (CL/F) of Maribavir for Adolescent Participants Only

    Time frame: Pre-morning dose, 1, 2, 3, 4, 6, 8, and 12 hours post-morning dose of Week 1

  16. Apparent Volume of Distribution (Vz/F) of Maribavir for Adolescent Participants Only

    Time frame: Pre-morning dose, 1, 2, 3, 4, 6, 8, and 12 hours post-morning dose of Week 1

Other outcomes

  1. Number of Participants Developing Resistance

    Resistance was defined as the presence of any CMV resistance-associated amino acid substitution that has been documented (or suspected) to be associated with reduced susceptibility to conventional anti-CMV therapies (ganciclovir/valganciclovir, foscarnet, and cidofovir) or maribavir. Genotypic resistance analyses were restricted to sequence variants that were known or suspected to be associated with resistance to conventional anti-CMV therapies or maribavir as of January 21, 2022. A participant was categorized as having developed resistance if the central lab genotyping results indicated the presence of one or more treatment-emergent resistance mutations.

    Time frame: From start of study drug up to end of the study (up to Week 20)

07

Results

Posted Mar 3, 2023

Participant flow

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).

Participant flow — Overall Study
MilestoneValganciclovir 900 mg BIDMaribavir 400 mg BID
Started277276
Treated participants274273
Participants received 8 weeks treatment140179
Completed217215
Not completed6061
Withdrew: Withdrawn consent2012
Withdrew: Death1831
Withdrew: Adverse event1310
Withdrew: Noncompliance52
Withdrew: Reason not specified46

Outcome measures

PrimaryNumber of Participants Who Achieved Confirmed Clearance of Plasma Cytomegalovirus (CMV) Deoxyribose Nucleic Acid (DNA) at the End of Study Week 8

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).

Time frame:
Week 8
Reported as:
Count of participants · Participants
Number of Participants Who Achieved Confirmed Clearance of Plasma Cytomegalovirus (CMV) Deoxyribose Nucleic Acid (DNA) at the End of Study Week 8
ParticipantsValganciclovir 900 mg BIDMaribavir 400 mg BID
Number of Participants Who Achieved Confirmed Clearance of Plasma Cytomegalovirus (CMV) Deoxyribose Nucleic Acid (DNA) at the End of Study Week 8212190
Statistical analysis
  • Valganciclovir 900 mg BID vs Maribavir 400 mg BID · Difference in percentage of responders: -7.7 · 95% CI -14.98 to -0.36Cochran-Mantel-Haenszel (CMH) weighted average approach (stratified for baseline plasma CMV DNA concentration and acute GVHD status) was used for adjusted difference in percentage of responders (Maribavir-Valganciclovir), 95% CI, and p-value.
SecondaryNumber 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

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). CMV Infection Symptom Control is defined as no new clinical findings of CMV tissue invasive disease. Maintenance of Treatment Effect is defined as maintaining confirmed CMV viremia clearance and CMV infection symptom control through Week 16.

Time frame:
Week 8 up to Week 16
Reported as:
Count of participants · Participants
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
ParticipantsValganciclovir 900 mg BIDMaribavir 400 mg BID
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 16133144
Statistical analysis
  • Valganciclovir 900 mg BID vs Maribavir 400 mg BID · Difference in percentage of responders: 4.4 · 95% CI -3.91 to 12.76CMH 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.
SecondaryNumber of Participants Who Achieved Confirmed Clearance of Plasma CMV DNA (CMV Viremia Clearance) at Week 8 After Receiving 8 Weeks of Study Assigned Treatment

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.

Time frame:
Week 8
Reported as:
Count of participants · Participants
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
ParticipantsValganciclovir 900 mg BIDMaribavir 400 mg BID
Number of Participants Who Achieved Confirmed Clearance of Plasma CMV DNA (CMV Viremia Clearance) at Week 8 After Receiving 8 Weeks of Study Assigned Treatment137158
Statistical analysis
  • Valganciclovir 900 mg BID vs Maribavir 400 mg BID · Cochran-Mantel-Haenszel · p = =0.061 (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.) · Difference in percentage of responders: 8.0 · 95% CI -0.38 to 16.30
SecondaryNumber of Participants Who Achieved Confirmed CMV Viremia Clearance After Receiving 8 Weeks of Study-assigned Treatment Through Weeks 12, 16 and 20

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.

Time frame:
Week 8 through Weeks 12, 16 and 20
Reported as:
Count of participants · Participants
Number of Participants Who Achieved Confirmed CMV Viremia Clearance After Receiving 8 Weeks of Study-assigned Treatment Through Weeks 12, 16 and 20
ParticipantsValganciclovir 900 mg BIDMaribavir 400 mg BID
Week 8137158
Week 1298134
Week 1682119
Week 207298
Statistical analysis
  • Valganciclovir 900 mg BID vs Maribavir 400 mg BID · Cochran-Mantel-Haenszel · p = =0.061 (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.) · Difference in percentage of responders: 8.0 · 95% CI -0.38 to 16.30
  • Valganciclovir 900 mg BID vs Maribavir 400 mg BID · Cochran-Mantel-Haenszel · p = =0.001 (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.) · Difference in percentage of responders: 13.4 · 95% CI 5.23 to 21.62
  • Valganciclovir 900 mg BID vs Maribavir 400 mg BID · Cochran-Mantel-Haenszel · p = <0.001 (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.) · Difference in percentage of responders: 13.8 · 95% CI 5.80 to 21.87
  • Valganciclovir 900 mg BID vs Maribavir 400 mg BID · Cochran-Mantel-Haenszel · p = =0.014 (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.) · Difference in percentage of responders: 9.7 · 95% CI 1.98 to 17.50
SecondaryNumber of Participants Who Maintained Confirmed CMV Viremia Clearance at Week 8 After Receiving Study-Assigned Treatment Through Study Weeks 12 and 20 Regardless of Whether Study Assigned Treatment Was Completed

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 the 8-week study-assigned treatment was completed or discontinued early) and had no symptoms of tissue invasive CMV disease at Week 8, Week 8 through Week 12, and Week 8 through Week 20, respectively.

Time frame:
Week 8 through Weeks 12 and 20
Reported as:
Count of participants · Participants
Number of Participants Who Maintained Confirmed CMV Viremia Clearance at Week 8 After Receiving Study-Assigned Treatment Through Study Weeks 12 and 20 Regardless of Whether Study Assigned Treatment Was Completed
ParticipantsValganciclovir 900 mg BIDMaribavir 400 mg BID
Week 8211190
Week 12157162
Week 20116118
Statistical analysis
  • Valganciclovir 900 mg BID vs Maribavir 400 mg BID · Cochran-Mantel-Haenszel · p = =0.051 (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.) · Difference in percentage of responders: -7.3 · 95% CI -14.64 to 0.02
  • Valganciclovir 900 mg BID vs Maribavir 400 mg BID · Cochran-Mantel-Haenszel · p = =0.606 (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.) · Difference in percentage of responders: 2.2 · 95% CI -6.05 to 10.37
  • Valganciclovir 900 mg BID vs Maribavir 400 mg BID · Cochran-Mantel-Haenszel · p = =0.809 (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.) · Difference in percentage of responders: 1.0 · 95% CI -7.27 to 9.31
SecondaryNumber of Participants With Confirmed Recurrence of Viremia During First 8 Weeks of the Study

Recurrence of CMV viremia is defined as plasma CMV DNA concentration greater than or equal to (\>=) 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 plasma samples at least 5 days apart, after being unquantifiable (\<LLOQ, i.e. \<137 IU/mL) 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.

Time frame:
Up to Week 8
Reported as:
Count of participants · Participants
Number of Participants With Confirmed Recurrence of Viremia During First 8 Weeks of the Study
ParticipantsValganciclovir 900 mg BIDMaribavir 400 mg BID
Number of Participants With Confirmed Recurrence of Viremia During First 8 Weeks of the Study616
SecondaryNumber of Participants With Confirmed Recurrence of Viremia During the Follow-up Period

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.

Time frame:
From Week 9 up to Week 20
Reported as:
Count of participants · Participants
Number of Participants With Confirmed Recurrence of Viremia During the Follow-up Period
ParticipantsValganciclovir 900 mg BIDMaribavir 400 mg BID
Number of Participants With Confirmed Recurrence of Viremia During the Follow-up Period4727
SecondaryNumber of Participants With Confirmed Recurrence of Viremia at Any Time During the Study

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.

Time frame:
Up to Week 20
Reported as:
Count of participants · Participants
Number of Participants With Confirmed Recurrence of Viremia at Any Time During the Study
ParticipantsValganciclovir 900 mg BIDMaribavir 400 mg BID
Number of Participants With Confirmed Recurrence of Viremia at Any Time During the Study5343
SecondaryNumber of Participants With Confirmed Recurrence of Viremia While on Study Treatment and Off Treatment

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.

Time frame:
Baseline up to Week 20
Reported as:
Count of participants · Participants
Number of Participants With Confirmed Recurrence of Viremia While on Study Treatment and Off Treatment
ParticipantsValganciclovir 900 mg BIDMaribavir 400 mg BID
On Study Treatment014
Off Study Treatment5329
SecondaryNumber of Participants With Grade 3 or 4 (Shift From Baseline Grade <3) and Grade 4 Neutropenia (Shift From Baseline Grade <4) While on Study Treatment

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.

Time frame:
From start of study drug to end of study drug + 1 day (up to approximately Week 8)
Reported as:
Count of participants · Participants
Number of Participants With Grade 3 or 4 (Shift From Baseline Grade <3) and Grade 4 Neutropenia (Shift From Baseline Grade <4) While on Study Treatment
ParticipantsValganciclovir 900 mg BIDMaribavir 400 mg BID
Grade 3 or Grade 4 Neutropenia137 (44.08 to 55.92)44 (11.76 to 20.48)
Grade 4 Neutropenia61 (17.34 to 27.19)9 (1.18 to 5.41)
SecondaryNumber of Participants With Treatment-Emergent Adverse Events During the On-Treatment Period

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).

Time frame:
From the start of the study treatment to 7 days after the last dose of study treatment (up to approximately Week 9)
Reported as:
Count of participants · Participants
Number of Participants With Treatment-Emergent Adverse Events During the On-Treatment Period
ParticipantsValganciclovir 900 mg BIDMaribavir 400 mg BID
Number of Participants With Treatment-Emergent Adverse Events During the On-Treatment Period269268
SecondaryPredose Concentration (Cmin) of Maribavir

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.

Time frame:
Weeks 1, 4, and 8: pre-morning dose
Reported as:
Mean · micrograms per milliliter (µg/mL)
Predose Concentration (Cmin) of Maribavir
micrograms per milliliter (µg/mL)Maribavir 400 mg BID
Week 19.17 ± 7.69
Week 48.71 ± 9.20
Week 87.02 ± 6.35
SecondaryArea Under the Concentration-Time Curve Over the 12-Hour Dosing Interval at Steady State AUC(0-tau) of Maribavir for Adolescent Participants Only
Time frame:
Pre-morning dose, 1, 2, 3, 4, 6, 8, and 12 hours post-morning dose of Week 1
Reported as:
Mean · hours (h)*μg/mL
Area Under the Concentration-Time Curve Over the 12-Hour Dosing Interval at Steady State AUC(0-tau) of Maribavir for Adolescent Participants Only
hours (h)*μg/mLMaribavir 400 mg BID
Area Under the Concentration-Time Curve Over the 12-Hour Dosing Interval at Steady State AUC(0-tau) of Maribavir for Adolescent Participants Only161 (161 to 161)
SecondaryMaximum Observed Plasma Concentration (Cmax) of Maribavir for Adolescent Participants Only
Time frame:
Pre-morning dose, 1, 2, 3, 4, 6, 8, and 12 hours post-morning dose of Week 1
Reported as:
Mean · µg/mL
Maximum Observed Plasma Concentration (Cmax) of Maribavir for Adolescent Participants Only
µg/mLMaribavir 400 mg BID
Maximum Observed Plasma Concentration (Cmax) of Maribavir for Adolescent Participants Only22.0 (22.0 to 22.0)
SecondaryTime When Maximum Concentration is Observed (Tmax) of Maribavir for Adolescent Participants Only
Time frame:
Pre-morning dose, 1, 2, 3, 4, 6, 8, and 12 hours post-morning dose of Week 1
Reported as:
Median · hours (h)
Time When Maximum Concentration is Observed (Tmax) of Maribavir for Adolescent Participants Only
hours (h)Maribavir 400 mg BID
Time When Maximum Concentration is Observed (Tmax) of Maribavir for Adolescent Participants Only0.92 (0.92 to 0.92)
SecondaryApparent Oral Clearance (CL/F) of Maribavir for Adolescent Participants Only
Time frame:
Pre-morning dose, 1, 2, 3, 4, 6, 8, and 12 hours post-morning dose of Week 1
Reported as:
Mean · liters per hour (L/h)
Apparent Oral Clearance (CL/F) of Maribavir for Adolescent Participants Only
liters per hour (L/h)Maribavir 400 mg BID
Apparent Oral Clearance (CL/F) of Maribavir for Adolescent Participants Only2.49 (2.49 to 2.49)
SecondaryApparent Volume of Distribution (Vz/F) of Maribavir for Adolescent Participants Only
Time frame:
Pre-morning dose, 1, 2, 3, 4, 6, 8, and 12 hours post-morning dose of Week 1
Reported as:
Mean · liters (L)
Apparent Volume of Distribution (Vz/F) of Maribavir for Adolescent Participants Only
liters (L)Maribavir 400 mg BID
Apparent Volume of Distribution (Vz/F) of Maribavir for Adolescent Participants Only18.3 (18.3 to 18.3)
Other pre-specifiedNumber of Participants Developing Resistance

Resistance was defined as the presence of any CMV resistance-associated amino acid substitution that has been documented (or suspected) to be associated with reduced susceptibility to conventional anti-CMV therapies (ganciclovir/valganciclovir, foscarnet, and cidofovir) or maribavir. Genotypic resistance analyses were restricted to sequence variants that were known or suspected to be associated with resistance to conventional anti-CMV therapies or maribavir as of January 21, 2022. A participant was categorized as having developed resistance if the central lab genotyping results indicated the presence of one or more treatment-emergent resistance mutations.

Time frame:
From start of study drug up to end of the study (up to Week 20)
Reported as:
Count of participants · Participants
Number of Participants Developing Resistance
ParticipantsValganciclovir 900 mg BIDMaribavir 400 mg BID
Number of Participants Developing Resistance824

Adverse events

Collected over 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). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Valganciclovir 900 mg BID29/277 (10.5%)95/274 (34.7%)256/274 (93.4%)
Maribavir 400 mg BID37/276 (13.4%)88/273 (32.2%)245/273 (89.7%)
Most frequent serious events
Showing 10 of 144
Most frequent serious events
EventValganciclovir 900 mg BIDMaribavir 400 mg BID
PyrexiaGeneral disorders13/2748/273
Acute graft versus host disease in intestineImmune system disorders4/27410/273
Febrile neutropeniaBlood and lymphatic system disorders8/2741/273
DiarrhoeaGastrointestinal disorders6/2744/273
Cystitis haemorrhagicRenal and urinary disorders5/2742/273
Acute graft versus host disease in skinImmune system disorders1/2744/273
Thrombotic microangiopathyBlood and lymphatic system disorders0/2744/273
Cytomegalovirus viraemiaInfections and infestations4/2741/273
Cytomegalovirus infectionInfections and infestations3/2743/273
DyspnoeaRespiratory, thoracic and mediastinal disorders2/2743/273
Most frequent other events
Showing 10 of 29
Most frequent other events
EventValganciclovir 900 mg BIDMaribavir 400 mg BID
NeutropeniaBlood and lymphatic system disorders144/27444/273
NauseaGastrointestinal disorders64/27474/273
AnaemiaBlood and lymphatic system disorders49/27462/273
ThrombocytopeniaBlood and lymphatic system disorders62/27431/273
VomitingGastrointestinal disorders47/27455/273
DiarrhoeaGastrointestinal disorders44/27450/273
DysgeusiaNervous system disorders16/27447/273
Acute graft versus host disease in skinImmune system disorders32/27446/273
HeadacheNervous system disorders14/27430/273
Neutrophil count decreasedInvestigations29/27413/273

Baseline characteristics

Randomized set included all participants in the enrolled set for whom a randomization number had been assigned.

Age, Continuous
Age, Continuous(years)Valganciclovir 900 mg BIDMaribavir 400 mg BIDTotal
Mean51.8 ± 15.2253.1 ± 13.9652.5 ± 14.61
Sex: Female, Male
Sex: Female, Male(Participants)Valganciclovir 900 mg BIDMaribavir 400 mg BIDTotal
Female110126236
Male167150317
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Valganciclovir 900 mg BIDMaribavir 400 mg BIDTotal
Hispanic or Latino373572
Not Hispanic or Latino193216409
Unknown or Not Reported472572
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Valganciclovir 900 mg BIDMaribavir 400 mg BIDTotal
American Indian or Alaska Native101
Asian393675
Native Hawaiian or Other Pacific Islander303
Black or African American91019
White200221421
More than one race000
Unknown or Not Reported25934
Region of Enrollment
Region of Enrollment(Participants)Valganciclovir 900 mg BIDMaribavir 400 mg BIDTotal
Australia131932
China9918
Korea, South325
New Zealand10717
Belgium313061
Switzerland426
Czech Republic022
Germany91120
Spain6169130
France341448
United Kingdom141428
Greece101
Croatia448
Hungary213
Israel224
Italy7411
Poland123
Russia101
Turkey6511
Canada8715
United States5061111
Singapore71118
Height
Height(cm)Valganciclovir 900 mg BIDMaribavir 400 mg BIDTotal
Mean169.58 ± 9.391168.75 ± 9.579169.17 ± 9.486
Weight
Weight(kg)Valganciclovir 900 mg BIDMaribavir 400 mg BIDTotal
Mean70.31 ± 15.24770.98 ± 16.77970.65 ± 16.027
Body Mass Index (BMI)
Body Mass Index (BMI)(kg/m^2)Valganciclovir 900 mg BIDMaribavir 400 mg BIDTotal
Mean24.38 ± 4.62824.90 ± 5.00724.64 ± 4.825
08

Study locations

129 sites
  • University of Alabama at Birmingham
    Birmingham, Alabama 35294, United States
  • UCLA Medical Center
    Los Angeles, California 90095, United States
  • Stanford University
    Stanford, California 94305, United States
  • Colorado Blood Cancer Institute - PPDS
    Denver, Colorado 80218, United States
  • Yale University School of Medicine
    New Haven, Connecticut 06520, United States
  • Emory University
    Atlanta, Georgia 30322, United States
  • University of Chicago
    Chicago, Illinois 60637, United States
  • Loyola University Medical Center
    Maywood, Illinois 60153, United States
  • University of Maryland School of Medicine
    Baltimore, Maryland 21201, United States
  • Johns Hopkins Hospital
    Baltimore, Maryland 21205, United States
  • Beth Israel Deaconess Medical Center
    Boston, Massachusetts 02115, United States
  • Brigham and Womens Hospital
    Boston, Massachusetts 02115, United States
  • UMass Memorial Medical Center
    Worcester, Massachusetts 01655, United States
  • Harper University Hospital
    Detroit, Michigan 48201, United States
  • Henry Ford Health System
    Detroit, Michigan 48202, United States
  • University of Minnesota
    Minneapolis, Minnesota 55454, United States
  • Mayo Clinic - PIN
    Rochester, Minnesota 59905, United States
  • Hackensack University Medical Center
    Hackensack, New Jersey 07601, United States
  • Joan and sandford I. Weill Medical College of Cornell University Clinic
    New York, New York 10021, United States
  • Columbia University Medical Center
    New York, New York 10032, United States
  • Memorial Sloan Kettering Cancer Center
    New York, New York 10065, United States
  • University of Pennsylvania
    Philadelphia, Pennsylvania 19104, United States
  • TriStar Centennial Medical Center
    Nashville, Tennessee 37203-1624, United States
  • Saint Davids South Austin Medical Center
    Austin, Texas 78704, United States
  • University of Texas MD Anderson Cancer Center
    Houston, Texas 77030, United States
  • Texas Transplant Institute
    San Antonio, Texas 78229, United States
  • VA Puget Sound Health Care System - NAVREF - PPDS
    Seattle, Washington 98108, United States
  • The Medical College of Wisconsin, Inc.
    Milwaukee, Wisconsin 53226, United States
  • Westmead Hospital
    Westmead, New South Wales 2145, Australia
  • Royal Adelaide Hospital
    Adelaide, South Australia 5000, Australia
  • Royal Melbourne Hospital
    Parkville, Victoria 3050, Australia
  • Medizinische Universitat Wien (Medical University of Vienna)
    Vienna, Wien, Austria
  • Elisabethinen Hospital Linz
    Linz, 4020, Austria
  • UZ Antwerpen
    Edegem, Antwerpen 2650, Belgium
  • Institute Jules Bordet
    Bruxelles, Brussels 1000, Belgium
  • Cliniques Universitaires Saint-Luc
    Bruxelles, Brussels 1200, Belgium
  • Universitair Ziekenhuis Brussel - PIN
    Jette, Brussels 1090, Belgium
  • University Hospital Gent
    Gent, Oost-Vlaanderen 9000, Belgium
  • UZ Leuven
    Leuven, Vlaams Brabant 3000, Belgium
  • AZ Sint-Jan AV
    Brugge, West-Vlaanderen 8000, Belgium
  • CHU de Liège
    Liège, 4000, Belgium
  • Vancouver General Hospital
    Vancouver, British Columbia V5Z 1M9, Canada
  • Queen Elizabeth II Health Sciences Center
    Halifax, Nova Scotia B3H 2Y9, Canada
  • Hamilton Health Sciences Corporation
    Hamilton, Ontario L8N 3Z5, Canada
  • Peking University First Hospital
    Beijing, Beijing 100034, China
  • Peking University People's Hospital
    Beijing, Beijing 100044, China
  • Nanfang Hospital Southern Medical University
    Guangzhou, Guangdong 510515, China
  • The First Affiliated Hospital of Soochow University
    Suzhou, Jiangsu 215006, China
  • Xiangya Hospital Central South University
    Changsha, 410008, China
  • Guangzhou First People's Hospital
    Guangzhou, 510180, China
  • The First Affiliated Hospital, College of Medicine, Zhejiang University
    Hangzhou Zhejiang, 310003, China
  • Henan Cancer Hospital
    Zhengzhou, 450008, China
  • University Hospital Center Zagreb
    Zagreb, 10000, Croatia
  • Fakultni nemocnice v Motole
    Prague, Praha, Hlavní Mesto 150 00, Czechia
  • Ustav hematologie a krevni transfuze
    Praha, 128 20, Czechia
  • Institut de Cancérologie Strasbourg Europe
    Strasbourg Cedex, Bas-Rhin 67033, France
  • Hopital de Hautepierre
    Strasbourg Cedex, Bas-Rhin 67098, France
  • CHU de Bordeaux
    Pessac, Gironde 33604, France
  • Hôpital Universitaire Dupuytren
    Limoges, Haute-Vienne 87042, France
  • CHU de GRENOBLE
    GRENOBLE Cedex 9, Isère 38043, France
  • Hôtel Dieu
    Nantes, Loire-Atlantique 44093, France
  • CHU Angers
    Angers Cedex 9, Maine-et-Loire 49933, France
  • Hopital Henri Mondor
    Créteil, Val-de-Marne 94010, France
  • Hopital Jean Minjoz
    Besnçon, 25030, France
  • Institut Paoli Calmettes
    Nice, 7120, France
  • Hôpital Saint Antoine
    Paris, 75012, France
  • Hôpital Saint Louis
    Paris, 75475, France
  • EDOG - Institut Claudius Regaud - PPDS
    Toulouse cedex 9, 31059, France
  • Universitätsklinikum Münster
    Muenster, Nordrhein-Westfalen 48149, Germany
  • Universitätsmedizin der Johannes Gutenberg-Universität Mainz
    Mainz, Rheinland-Pfalz 55131, Germany
  • Universität des Saarlandes
    Homburg, Saarland 66424, Germany
  • Universitatsklinikum Leipzig
    Leipzig, Sachsen 04103, Germany
  • Universitätsklinikum Augsburg
    Augsburg, 86156, Germany
  • Helios Klinikum Berlin-Buch
    Berlin, 13125, Germany
  • Martin Luther Universitat Halle Wittenberg
    Halle, 6120, Germany
  • Universitätsklinikum Hamburg Eppendorf
    Hamburg, 20251, Germany
  • Universitätsklinik Rostock
    Rostock, Germany
  • Robert Bosch Krankenhaus
    Stuttgart, 70376, Germany
  • Universitätsklinikum Tübingen
    Tübingen, 72076, Germany
  • Attikon University General Hospital
    Athina, Attiki 124 64, Greece
  • Georgios Papanikolaou General Hospital of Thessaloniki
    Thessaloniki, 57010, Greece
  • Del-pesti Centrumkorhaz- Orszagos Hematologiai és Infektologiai Intezet
    Budapest, 1097, Hungary
  • Sheba Medical Center - PPDS
    Ramat Gan, HaMerkaz 5262000, Israel
  • Hadassah Medical Center - PPDS
    Jerusalem, Yerushalayim 90000, Israel
  • Rambam Medical Center - PPDS
    Haifa, 31999, Israel
  • Tel Aviv Sourasky Medical Center PPDS
    Tel-Aviv, 64239, Israel
  • Ospedale Dell'Angelo
    Brescia, Lombardia 30174, Italy
  • Ospedale Infantile Regina Margherita - INCIPIT - PIN
    Torino, Piemonte 10126, Italy
  • Azienda Ospedaliera Universitaria Integrata Di Verona
    Verona, Veneto 37134, Italy
  • Azienda Ospedaliera Universitaria Careggi
    Firenze, 50134, Italy
  • Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
    Milano, 20122, Italy
  • Fondazione Policlinico Universitario A Gemelli
    Roma, 00168, Italy
  • Azienda Ospedaliera Città della Salute e della Scienza di Torino
    Torino, 10126, Italy
  • Dong-A University Hospital
    Busan, 49201, Korea, Republic of
  • Keimyung University Dongsan Hospital
    Daegu, 41931, Korea, Republic of
  • Auckland City Hospital
    Grafton, Auckland 1023, New Zealand
  • Canterbury Health Laboratories
    Christchurch, South Island 8011, New Zealand
  • Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we Wroclawiu
    Wroclaw, Dolnoslaskie 50-367, Poland
  • MTZ Clinical Research Sp z o o - PRATIA - PPDS
    Warszawa, Mazowieckie 02-106, Poland
  • Uniwersyteckie Centrum Kliniczne
    Gdansk, 80-214, Poland

Showing the first 100 of 129 sites across 23 countries.

09

References and documents

Study documents

  • Study protocol · Sep 15, 2021
  • Statistical analysis plan · Apr 27, 2022

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.

Supporting information: Study protocol, Sap, Icf, Csr

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Mar 3, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02927067
Lead sponsor
Shire
Collaborators
Takeda Development Center Americas, Inc.
Responsible party
Sponsor
First posted
Oct 6, 2016
Start date
Apr 14, 2017
Primary completion
Jul 1, 2022
Completion
Jul 1, 2022
Results posted
Mar 3, 2023
Last update
Mar 3, 2023

Study contacts

Study Director
study director · Shire

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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