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Study for the Treatment of Cytomegalovirus (CMV) Infection in Hematopoietic Stem Cell Transplant Recipients

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ClinicalTrials.gov Identifier: NCT02927067
Recruitment Status : Recruiting
First Posted : October 6, 2016
Last Update Posted : July 17, 2018
Sponsor:
Information provided by (Responsible Party):
Shire

Brief Summary:
The purpose of this study is to compare the efficacy and safety of maribavir to valganciclovir for the treatment of cytomegalovirus (CMV) infection in asymptomatic hematopoietic stem cell transplant recipients.

Condition or disease Intervention/treatment Phase
Cytomegalovirus (CMV) Drug: Maribavir Drug: Valganciclovir Drug: Placebo Phase 3

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 550 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : April 6, 2017
Estimated Primary Completion Date : August 13, 2021
Estimated Study Completion Date : August 13, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Maribavir/ Placebo
200mg tablets administered orally at 400mg (2 tablets) twice daily with food and placebo tablets (2 tablets) with the same appearance and route of administration as valganciclovir
Drug: Maribavir
200mg tablets

Drug: Placebo
Placebo tablets with the same appearance and route of administration as either maribavir or valganciclovir

Active Comparator: Valganciclovir/ Placebo
450mg tablets administered orally at 900mg (2 tablets) twice daily with food and placebo tablets (2 tablets) with the same appearance and route of administration as maribavir
Drug: Valganciclovir
450mg tablets

Drug: Placebo
Placebo tablets with the same appearance and route of administration as either maribavir or valganciclovir




Primary Outcome Measures :
  1. EFFICACY OF MARIBAVIR COMPARED TO VALGANCICLOVIR IN CONFMIRMED CMV VIREMIA CLEARANCE AT THE END OF STUDY WEEK 8, REGARDLESS OF WHETHER STUDY ASSIGNED TREATMENT WAS COMPLETED [ Time Frame: 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 Millilitre [IU/mL]), when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV Test in 2 consecutive post baseline samples separated by at least 5 days. The patient must have received exclusively study-assigned treatment.


Secondary Outcome Measures :
  1. MAINTENANCE OF CONFIRMED CMV VIREMIA CLEARANCE ACHIEVED AT THE END OF STUDY WEEK 8 THROUGH STUDY WEEK 16. [ Time Frame: Week 8 through Week 16 ]
    Confirmed CMV viremia clearance is defined as plasma CMV DNA concentrations <LLOQ (<137 IU/mL), when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV Test in 2 consecutive post baseline samples separated by at least 5 days. It will be measured from plasma CMV DNA by quantitative PCR assay. The patient must have received exclusively study-assigned treatment.

  2. ACHIEVEMENT CONFIRMED CMV VIREMIA CLEARANCE AFTER 8 WEEKS OF RECEIVING STUDY-ASSIGNED TREATMENT [ Time Frame: Week 8 ]
    Confirmed CMV viremia clearance is defined as plasma CMV DNA concentrations <LLOQ (<137 IU/mL), when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV Test in 2 consecutive post baseline samples separated by at least 5 days. It will be measured from plasma CMV DNA by quantitative PCR assay.

  3. MAINTENANCE OF CONFIRMED CMV VIREMIA CLEARANCE, ACHIEVED AFTER COMPLETION OF 8 WEEKS OF STUDY-ASSIGNED TREATMENT THROUGH STUDY WEEKS 12, 16 AND 20 [ Time Frame: Week 8, Week 12, Week 16 and Week 20 ]
    Confirmed CMV viremia clearance is defined as plasma CMV DNA concentrations <LLOQ (<137 IU/mL), when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV Test in 2 consecutive post baseline samples separated by at least 5 days. It will be measured from plasma CMV DNA by quantitative PCR assay.

  4. MAINTENANCE OF CONFIRMED CMV VIREMIA CLEARANCE ACHIEVED AT THE END OF STUDY WEEK 8 WEEK THROUGH STUDY WEEKS 12, 16 AND 20, REGARDLESS OF WHETHER STUDY ASSIGNED TREATMENT WAS COMPLETED. [ Time Frame: Week 8, Week 12 and Week 20 ]
    Confirmed CMV viremia clearance is defined as plasma CMV DNA concentrations <LLOQ (<137 IU/mL), when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV Test in 2 consecutive post baseline samples separated by at least 5 days. It will be measured from plasma CMV DNA by quantitative PCR assay.

  5. RECURRENCE OF CONFIRMED CMV VIREMIA IN THE 2 STUDY TREATMENT ARMS WHEN SUBJECTS ARE ON TREATMENT AND OFF TREATMENT [ Time Frame: Baseline up to Week 20 ]
    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 followup study phase, and at any time during the study.

  6. Incidence of Grade 3 or 4 Neutropenia [ Time Frame: Baseline up to Week 8 ]
    Grade 3 and grade 4 neutropenia are defined as absolute neutophil count (ANC) <1000/ cubiv millimeter (mm^3) and ANC <500/mm^3 respectively.

  7. Safety and Tolerability of Maribavir Compared to Valganciclovir [ Time Frame: Baseline up to Week 20 ]
    Adverse events (AEs), vital signs, physical examinations and clinical laboratory tests will be assessed.

  8. Pharmacokinetics (PK) of maribavir [ Time Frame: Week 8 ]
    AUC, Cmax, and Cmin will be assessed



Information from the National Library of Medicine

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Ages Eligible for Study:   16 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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 subject before completing any study-related procedures.
  2. Be greater than or equal to (>=) 16 years of age at the time of consent.
  3. Be a recipient of hematopoietic stem cell transplant.
  4. Have a documented asymptomatic CMV infection, with a screening value of CMV DNA >=2730 IU/mL to less than or equal to (<=) 273000 IU/mL in whole blood or >=910 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.
  5. Have the current CMV infection as the first episode of CMV viremia after HSCT, either primary or reactivation.
  6. Per investigator's judgment, be eligible for treatment with valganciclovir.
  7. 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 >=1000/mm^3 [1.0 x 10^9/ liter (L)]
    2. Platelet count >=25,000/mm^3 [25 x 10^9/L]
    3. Hemoglobin >=8 gram per deciliter (g/dL).
    4. Estimated creatinine clearance >=60mL/min/1.73 square meter (m^2)
  8. Have a negative serum beta human chorionic gonadotropin (β-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.
  9. Be able to swallow tablets.
  10. Have life expectancy of >=8 weeks.
  11. Weigh >=40 kg.
  12. Be willing and have an understanding and ability to fully comply with study procedures and restrictions defined in the protocol.

Exclusion Criteria:

  1. Have CMV tissue invasive disease as assessed by the investigator at the time of screening and randomization at Visit 2/Day 0.
  2. Have a CMV infection that is known to be genotypically resistant to ganciclovir, valganciclovir, foscarnet, or cidofovir based on documented evidence.
  3. Be presenting with recurrent CMV infection (defined as a new detection of CMV infection in a subject who had at least one previously documented episode of CMV infection posttransplant, 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 subject 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.
  4. Require ganciclovir, valganciclovir, foscarnet, or cidofovir administration for conditions other than CMV when study treatment is initiated (example: herpes simplex virus [HSV] coinfection requiring use of any of these agents after the randomization) or would need a co-administration with maribavir for CMV infection.
  5. Be receiving leflunomide, or artesunate when study treatment is initiated. Note: Subjects 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. Subjects receiving artesunate must discontinue the use prior to the first dose of study treatment.
  6. Be on treatment with anti-CMV agents (ganciclovir, valganciclovir, foscarnet or cidofovir) for the current CMV infection for longer than 72 hours.

    Note: A subject who is receiving these anti-CMV agents must discontinue their use before the first dose of study treatment. A subjects who may be receiving cidofovir must discontinue this antiviral at least 14 days prior to randomization at Visit 2/Day 0 and the first dose of study treatment.

    Note: Subjects who were administered these anti-CMV agents for prophylaxis, should have these treatments completed at least 2 weeks prior to the study entry or start of the treatment for current infection, whichever comes first and have undetectable CMV DNA (based on local laboratory) for at least two weeks between the completion of this treatment and onset of the current infection.

  7. Have known hypersensitivity to the active substance or to an excipient of the study treatments.
  8. 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.
  9. Require mechanical ventilation or vasopressors for hemodynamic support at the time of randomization.
  10. Be female and pregnant or nursing.
  11. Have previously completed, discontinued, or have been withdrawn from this study.
  12. Have received any investigational agent with known anti-CMV activity within 30 days before initiation of study treatment or CMV vaccine at any time.
  13. Have received any unapproved agent or device within 30 days before initiation of study treatment.
  14. 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 subject.
  15. Have previously received maribavir.
  16. Have serum aspartate aminotransferase (AST) >5 times upper limit of normal (ULN) at screening, or serum alanine aminotransferase (ALT) >5 times ULN at screening, or total bilirubin >=3.0 x ULN at screening (except for documented Gilbert's syndrome), as analyzed by local or central lab.
  17. Have known (previously documented) positive results for human immunodeficiency virus (HIV).
  18. Have active malignancy with the exception of nonmelanoma skin cancer, as determined by the investigator. Subjects who experience relapse or progression of their underlying malignancy (for which HSCT was performed), as determined by the investigator, are not to be enrolled.
  19. Be undergoing treatment for acute or chronic hepatitis C.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02927067


Contacts
Contact: Shire Contact 866-842-5335 ClinicalTransparency@shire.com

  Show 89 Study Locations
Sponsors and Collaborators
Shire
Investigators
Study Director: Shire Director Shire

Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT02927067     History of Changes
Other Study ID Numbers: SHP620-302
2015-004726-34 ( EudraCT Number )
First Posted: October 6, 2016    Key Record Dates
Last Update Posted: July 17, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Valganciclovir
Ganciclovir
Antiviral Agents
Anti-Infective Agents