Efficacy and Safety Study of Maribavir Treatment Compared to Investigator-assigned Treatment in Transplant Recipients With Cytomegalovirus (CMV) Infections That Are Refractory or Resistant to Treatment With Ganciclovir, Valganciclovir, Foscarnet, or Cidofovir
NCT ID: NCT02931539
Last Updated: 2021-11-03
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE3
352 participants
INTERVENTIONAL
2016-12-22
2020-08-17
Brief Summary
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Maribavir Treatment
Participants will receive 400 milligrams (mg) (2x200 mg tablets) maribavir twice daily orally (doses separated by a minimum of 8 hours) for 8 weeks.
Maribavir
Maribavir 400 milligrams (mg) (2x200 mg tablets) will be administered twice daily for 8 weeks.
Investigator-Assigned Treatment
Participants will receive anti-CMV agent best suited to treat the respective participant as per the investigator's prescribed dosing regimen for 8 weeks. Agents of choice include: ganciclovir, valganciclovir, foscarnet, or cidofovir.
Ganciclovir
Ganciclovir as per the investigator's prescribed dosing regimen will be administered for 8 weeks.
Valganciclovir
Valganciclovir as per the investigator's prescribed dosing regimen will be administered for 8 weeks.
Foscarnet
Foscarnet as per the investigator's prescribed dosing regimen will be administered for 8 weeks.
Cidofovir
Cidofovir as per the investigator's prescribed dosing regimen will be administered for 8 weeks.
Interventions
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Maribavir
Maribavir 400 milligrams (mg) (2x200 mg tablets) will be administered twice daily for 8 weeks.
Ganciclovir
Ganciclovir as per the investigator's prescribed dosing regimen will be administered for 8 weeks.
Valganciclovir
Valganciclovir as per the investigator's prescribed dosing regimen will be administered for 8 weeks.
Foscarnet
Foscarnet as per the investigator's prescribed dosing regimen will be administered for 8 weeks.
Cidofovir
Cidofovir as per the investigator's prescribed dosing regimen will be administered for 8 weeks.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
2. The participant must be a recipient of hematopoietic stem cell or solid organ transplant.
3. The participant must have a documented CMV infection in whole blood or plasma, with a screening value of greater than or equal to (\>=) 2730 international units per milliliter (IU/mL) in whole blood or \>= 910 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. The same laboratory and same sample type (whole blood or plasma) must be used for these assessments.
4. The participant must have a current CMV infection that is refractory to the most recently administered of the four anti-CMV treatment agents. Refractory is defined as documented failure to achieve greater than (\>) 1 log10 (common logarithm to base 10) decrease in CMV DNA level in whole blood or plasma after a 14 day or longer treatment period with intravenous (IV) ganciclovir/oral valganciclovir, IV foscarnet, or IV cidofovir.
a. Participants with documentation of 1 or more CMV genetic mutations associated with resistance to ganciclovir/valganciclovir, foscarnet, and/or cidofovir must also meet the definition of refractory CMV infection.
5. The Investigator must be willing to treat the participant with at least one of the available anti-CMV drugs (ganciclovir, valganciclovir, foscarnet, or cidofovir). Note: Combination therapy with foscarnet and cidofovir is not permitted in the investigator-assigned anti-CMV treatment (IAT) arm due to the potential for serious nephrotoxicity.
6. The participant must be \>= 12 years of age at the time of consent.
7. The participant must weigh \>= 35 kilogram (kg).
8. The participant must 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 (ANC) \>= 1000/ millimeter cube (mm\^3) (1.0 x 10\^9/liter \[L\])
2. Platelet count \>= 25,000/mm\^3 \[25 x 10\^9/L\],
3. Hemoglobin \>= 8 grams per deciliter (g/dL).
4. Estimated glomerular filtration rate (eGFR) \> 30 (milliliters per minute (mL/min) /1.73 square meter (m\^2) as assessed by Modification of Diet in Renal Disease (MDRD) formula for participants \>= 18 years of age or Schwartz formula for participants less than (\<) 18 years of age.
9. The participant must have a negative serum beta-human chorionic gonadotropin (beta-HCG) pregnancy test at screening, if a female of child bearing potential. Additional urine pregnancy tests may be done per institutional requirements. 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 if treated with maribavir, ganciclovir, valganciclovir, or cidofovir and for 180 days afterward if treated with foscarnet.
10. The participant must be able to swallow tablets, or receive tablets crushed and/or dispensed in water via nasogastric or orogastric tube.
11. The participant must be willing and have an understanding and ability to fully comply with study procedures and restrictions defined in the protocol.
12. The participant must be willing to provide necessary samples (example \[e.g,\] biopsy) for the diagnosis of tissue invasive CMV disease at baseline as determined by the Investigator.
13. The participant must have a life expectancy of \>= 8 weeks.
Exclusion Criteria
2. 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 coadministration with maribavir for CMV infection. NOTE: A participant who is not continuing with the same anti-CMV drug(s) (ganciclovir, valganciclovir or foscarnet) for the study treatment (if randomized to the investigator assigned anti-CMV treatment arm), must discontinue their use before the first dose of study drug. If participant is currently being treated with cidofovir and is assigned another anti-CMV therapy by the investigator, the participant must discontinue its use at least 14 days prior to randomization at Visit 2/Day 0 and the first dose of study treatment.
3. Be receiving leflunomide, letermovir, or artesunate when study treatment is initiated. NOTE: Participants 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 at least 3 days prior to the first dose of study treatment. Participants receiving artesunate must discontinue the use prior to the first dose of study treatment.
4. 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/enteral medication.
5. Have known hypersensitivity to the active substance or to an excipient for a study treatment.
6. Have tissue invasive CMV disease with central nervous system involvement including the retina (example, CMV retinitis).
7. 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), by local or central lab. Participants with biopsy confirmed CMV hepatitis will not be excluded from study participation despite AST or ALT \> 5 times ULN at screening.
8. Have known 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.
9. Require mechanical ventilation or vasopressors for hemodynamic support at the time of enrollment.
10. Be female and pregnant or breast feeding.
11. Have previously received maribavir.
12. Have received any investigational agent with known anti-CMV activity within 30 days before initiation of study treatment or investigational CMV vaccine at any time.
13. Have received any unapproved agent or device within 30 days before initiation of study treatment.
14. Have active malignancy with the exception of nonmelanoma skin cancer. Participants who have had a hematopoietic stem cell transplant (HSCT) and who experience relapse or progression of the malignancy as per investigator's opinion are not to be enrolled.
15. Be undergoing treatment for acute or chronic hepatitis C.
16. Have any clinically significant medical or surgical condition that, in the investigator's opinion, could interfere with the interpretation of study results, contraindicate the administration of the assigned study treatment, or compromise the safety or well-being of the participant.
12 Years
ALL
No
Sponsors
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Shire
INDUSTRY
Responsible Party
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Principal Investigators
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Study Director
Role: STUDY_DIRECTOR
Shire
Locations
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University of Alabama at Birmingham
Birmingham, Alabama, United States
University of Arizona
Tucson, Arizona, United States
City of Hope National Medical Center
Duarte, California, United States
University of Southern California
Los Angeles, California, United States
UCLA Medical Center
Los Angeles, California, United States
UC Davis Medical Center
Sacramento, California, United States
Stanford University
Stanford, California, United States
Yale University School of Medicine
New Haven, Connecticut, United States
AdventHealth
Orlando, Florida, United States
Emory University Hospital
Atlanta, Georgia, United States
Feinberg School of Medicine Northwestern University
Chicago, Illinois, United States
Loyola University Medical Center
Maywood, Illinois, United States
University of Chicago Medical Center
Maywood, Illinois, United States
University of Kentucky
Lexington, Kentucky, United States
Ochsner Clinic Foundation
New Orleans, Louisiana, United States
University of Maryland
Baltimore, Maryland, United States
Johns Hopkins Hospital
Baltimore, Maryland, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
Brigham and Womens Hospital
Boston, Massachusetts, United States
UMass Memorial Medical Center
Worcester, Massachusetts, United States
University of Michigan
Ann Arbor, Michigan, United States
Henry Ford Health System
Detroit, Michigan, United States
William Beaumont Hospital
Royal Oak, Michigan, United States
University of Minnesota
Minneapolis, Minnesota, United States
Mayo Clinic - PPDS
Rochester, Minnesota, United States
University of Nebraska Medical Center
Omaha, Nebraska, United States
Hackensack University Medical Center
Hackensack, New Jersey, United States
Columbia University Medical Center
New York, New York, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
New York Presbyterian Hospital - Weill-Cornell
New York, New York, United States
SUNY Upstate Medical Center
Syracuse, New York, United States
Duke University Medical Center
Durham, North Carolina, United States
The Christ Hospital
Cincinnati, Ohio, United States
University of Cincinnati
Cincinnati, Ohio, United States
Cincinnati Children's Hospital Medical Center - PIN
Cincinnati, Ohio, United States
University Hospitals Cleveland Medical Center
Cleveland, Ohio, United States
Nationwide Children's Hospital
Columbus, Ohio, United States
University of Pennsylvania
Philadelphia, Pennsylvania, United States
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States
Medical University of South Carolina - PPDS
Charleston, South Carolina, United States
St Jude Children's Research Hospital
Memphis, Tennessee, United States
University of Texas Southwestern Medical Center
Dallas, Texas, United States
Baylor All Saints Medical Center
Fort Worth, Texas, United States
Baylor College of Medicine
Houston, Texas, United States
MD Anderson Cancer Center
Houston, Texas, United States
University of Utah Health Sciences Center - PPDS
Salt Lake City, Utah, United States
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States
Westmead Hospital
Westmead, New South Wales, Australia
Monash Health, Monash Medical Centre
Clayton, Victoria, Australia
The Alfred Hospital
Melbourne, Victoria, Australia
Royal Melbourne Hospital
Parkville, Victoria, Australia
Sir Charles Gairdner Hospital
Nedlands, Washington, Australia
Princess Alexandra Hospital
Brisbane, , Australia
Tiroler Landeskrankenanstalten GmbH
Innsbruck, , Austria
Allgemeines Krankenhaus der Stadt Wien
Vienna, , Austria
UZ Antwerpen
Edegem, Antwerpen, Belgium
Institut Jules Bordet
Brussels, Brussels Capital, Belgium
UZ Gent
Ghent, Oost-Vlaanderen, Belgium
UZ Leuven
Leuven, Vlaams Brabant, Belgium
AZ Sint-Jan AV
Bruges, West-Vlaanderen, Belgium
ZNA Stuivenberg
Antwerp, , Belgium
Hôpital Erasme
Brussels, , Belgium
UZ Brussel
Brussels, , Belgium
University of Alberta
Edmonton, Alberta, Canada
Hamilton Health Sciences Corporation
Hamilton, Ontario, Canada
St. Joseph's Healthcare Hamilton
Hamilton, Ontario, Canada
Princess Margaret Hospital
Toronto, Ontario, Canada
University Health Network
Toronto, Ontario, Canada
Centre Hospitalier Universitaire Sainte-Justine
Montreal, Quebec, Canada
McGill University Health Center
Montreal, Quebec, Canada
University Hospital Center Zagreb
Zagreb, , Croatia
Copenhagen University Hospital
København Ø, Capital, Denmark
CHRU Brest - Hospital Cavale Blanche
Brest, Finistère, France
Hôpital de Rangueil
Toulouse, Haute-Garonne, France
Hopital Foch
Suresnes, Hauts-de-Seine, France
CHRU Rennes
Rennes, Ille-et-Vilaine, France
CHRU Bretonneau
Tours, Indre-et-Loire, France
CHRU Nantes
Nantes, Loire-Atlantique, France
Hôpital de La Croix Rousse
Lyon, Rhône, France
Centre Hospitalier Lyon Sud
Pierre-Bénite, Rhône, France
Hopital Henri Mondor
Créteil, Val-de-Marne, France
Hôpital Paul Brousse
Villejuif, Val-de-Marne, France
CHU Amiens Hôpital Sud
Amiens, , France
Hopital Gabriel Montpied
Clermont-Ferrand, , France
CHU de GRENOBLE
Grenoble, , France
CHRU Lille
Lille, , France
CHU Dupuytren
Limoges, , France
Groupement Hospitalier Edouard Herriot
Lyon, , France
Groupe Hospitalier Necker Enfants Malades
Paris, , France
Hôpital Saint Louis
Paris, , France
Hôpital Saint Antoine
Paris, , France
CHRU de Poitiers La Miletrie
Poitiers, , France
Institut de Cancerologie de la Loire
Saint-Priest-en-Jarez, , France
Hopital de Hautepierre
Strasbourg, , France
Hôpital Civil
Strasbourg, , France
University Clinic Heidelberg - PPDS
Heidelberg, Baden-Wurttemberg, Germany
Universitätsklinikum Erlangen
Erlangen, Bavaria, Germany
Universitätsklinikum Essen
Essen, North Rhine-Westphalia, Germany
Universitätsmedizin der Johannes Gutenberg-Universität Mainz
Mainz, Rhineland-Palatinate, Germany
Universitatsklinikum Leipzig
Leipzig, Saxony, Germany
Universitätsklinikum Erlangen
Erlangen, , Germany
University Clinic Heidelberg - PPDS
Heidelberg, , Germany
LMU Klinikum der Universität München
München, , Germany
Universitätsklinikum Tübingen
Tübingen, , Germany
Ospedale San Raffaele S.r.l. - PPDS
Milan, Lombardy, Italy
Istituto Europeo Di Oncologia
Milan, Lombardy, Italy
Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona-Umberto I G.M. Lancisi G. Salesi
Ancona, The Marches, Italy
Azienda Ospedaliero Universitaria di Parma
Parma, , Italy
Azienda Ospedaliero Universitaria Pisana
Pisa, , Italy
Fondazione Policlinico Universitario A Gemelli
Roma, , Italy
Azienda Sanitaria Universitaria Integrata di Udine
Udine, , Italy
Singapore General Hospital (SGH)
Singapore, , Singapore
Hospital Universitario Germans Trias i Pujol
Badalona, Barcelona, Spain
Hospital Universitario de Cruces
Barakaldo, , Spain
Fundacio Puigvert
Barcelona, , Spain
Hospital Universitario Vall d'Hebrón - PPDS
Barcelona, , Spain
Hospital de La Santa Creu i Sant Pau
Barcelona, , Spain
Hospital Universitario de Bellvitge
L'Hospitalet de Llobregat, , Spain
Hospital Universitario Puerta de Hierro - Majadahonda
Madrid, , Spain
Complejo Asistencial Universitario de Salamanca - H. Clinico
Salamanca, , Spain
Hospital Clinico Universitario de Valencia
Valencia, , Spain
Hospital Universitari i Politecnic La Fe de Valencia
Valencia, , Spain
Centre Hospitalier Universitaire Vaudois
Lausanne, Vaud (fr), Switzerland
University Hospital Coventry
Coventry, Birmingham, United Kingdom
Birmingham Heartlands Hospital
West Midlands, Birmingham, United Kingdom
Beatson West of Scotland Cancer Centre - PPDS
Glasgow, Glasgow City, United Kingdom
Imperial College Healthcare NHS Trust
London, London, City of, United Kingdom
Wythenshawe Hospital - PPDS
Wythenshawe, Manchester, United Kingdom
Sheffield Childrens Hospital
Sheffield, Yorkshire, United Kingdom
Royal Liverpool and Broadgreen University Hospitals NHS Trust
Liverpool, , United Kingdom
Guy's and St Thomas' NHS Foundation Trust - Guy's Hospital
London, , United Kingdom
Royal Free Hospital
London, , United Kingdom
Manchester Royal Infirmary - PPDS
Manchester, , United Kingdom
Churchill Hospital
Oxford, , United Kingdom
Countries
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References
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Rajagopalan K, Bullano M, Gelone D, Bo T, Taduka V, Syed SS. Real-world effectiveness and tolerability of post solid organ transplant patients with CMV switching from valganciclovir treatment to maribavir: analysis using lab-linked claims data in the United States. Expert Rev Anti Infect Ther. 2025 Aug;23(8):653-662. doi: 10.1080/14787210.2025.2517344. Epub 2025 Jun 27.
Blumberg EA, Witzke O, Harber M, Ison MG, Saliba F, Kamar N, Sundberg AK, Gu J, Kumar D, La Hoz RM. Maribavir for refractory cytomegalovirus infection (with or without resistance) in solid organ transplant recipients: Subgroup analysis of the phase 3 randomized SOLSTICE study. J Heart Lung Transplant. 2025 Jun;44(6):986-994. doi: 10.1016/j.healun.2024.11.026. Epub 2024 Nov 28.
Sun K, Fournier M, Sundberg AK, Song IH. Maribavir: Mechanism of action, clinical, and translational science. Clin Transl Sci. 2024 Jan;17(1):e13696. doi: 10.1111/cts.13696.
Chou S, Alain S, Cervera C, Chemaly RF, Kotton CN, Lundgren J, Papanicolaou GA, Pereira MR, Wu JJ, Murray RA, Buss NE, Fournier M. Drug Resistance Assessed in a Phase 3 Clinical Trial of Maribavir Therapy for Refractory or Resistant Cytomegalovirus Infection in Transplant Recipients. J Infect Dis. 2024 Feb 14;229(2):413-421. doi: 10.1093/infdis/jiad293.
Avery RK, Alain S, Alexander BD, Blumberg EA, Chemaly RF, Cordonnier C, Duarte RF, Florescu DF, Kamar N, Kumar D, Maertens J, Marty FM, Papanicolaou GA, Silveira FP, Witzke O, Wu J, Sundberg AK, Fournier M; SOLSTICE Trial Investigators. Maribavir for Refractory Cytomegalovirus Infections With or Without Resistance Post-Transplant: Results From a Phase 3 Randomized Clinical Trial. Clin Infect Dis. 2022 Sep 10;75(4):690-701. doi: 10.1093/cid/ciab988.
Del Pozo Martin Y. 47th Annual Meeting of the EBMT. Lancet Haematol. 2021 May;8(5):e317-e318. doi: 10.1016/S2352-3026(21)00104-6. Epub 2021 Mar 31. No abstract available.
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Related Links
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To obtain more information on the study, click here/on this link
Other Identifiers
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2015-004725-13
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
SHP620-303
Identifier Type: -
Identifier Source: org_study_id