A Study to Evaluate the Safety and Tolerability, Pharmacokinetics, and Antiviral Activity of Maribavir for the Treatment of Cytomegalovirus (CMV) Infection in Children and Adolescents Who Have Received a Hematopoietic Stem Cell Transplant (HSCT) or a Solid Organ Transplant (SOT)

Last updated: December 9, 2024
Sponsor: Takeda
Overall Status: Active - Not Recruiting

Phase

3

Condition

Cytomegalovirus Infections

Treatment

Maribavir

Clinical Study ID

NCT05319353
TAK-620-2004
2023-508988-73-00
2021-004279-15
jRCT2031230753
  • Ages < 17
  • All Genders

Study Summary

The main aim of this study is to find out the safety, tolerability and pharmacokinetics (PK) of maribavir for the treatment of CMV infection in children and teenagers after HSCT or SOT and to identify the optimal dose of maribavir using a 200 milligrams (mg) tablet formulation or powder for oral suspension.

The participants will be treated with maribavir for 8 weeks.

Participants need to visit their doctor during 12-week follow-up period.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Parent/both parents or legally authorized representative (LAR) must providesignature of informed consent and there must be documentation of assent by theparticipant, as age appropriate, before completing any study-related procedures.

  • Be a male or female child or adolescent < 18 years of age at the time of consent.For participants in Cohort 3 only (0 to <6 years) must have a gestational age of atleast 39 weeks and a minimum weight of 5 kg.

  • Be a recipient of an SOT or an HSCT that is functioning at the time of screening.

  • Have a documented CMV infection which may be a first episode of post-transplant CMVviremia (primary or reactivation) or refractory to other anti-CMV treatments, with aCMV DNA screening value of >= 1365 International Units per milliliter (IU/mL) inwhole blood or >= 455 IU/mL in plasma in 2 consecutive assessments separated by atleast 1 day, as determined by local laboratory quantitative polymerase chainreaction (qPCR) or comparable quantitative nucleic acid amplification test (qNAAT)results. Quantitative assays must be standardized to the World Health Organization (WHO) CMV International Standard. Both samples must be taken within 14 days of firstdose of study drug, with the second sample obtained within 5 days prior to firstdose of study drug. The same laboratory and same sample type (whole blood or plasma)must be used for both assessments. If documented and verified values are availablein medical history that fulfill this criterion entirely, they may be used instead.

  • Have all the following results as part of screening laboratory assessments:

  • Absolute neutrophil count >= 500 per cubic millimeter (/mm^3) (0.5 × 10^9 per liter [/L])

  • Platelet count >= 15,000/mm^3 (15 × 10^9/L)

  • Hemoglobin >= 8 grams per deciliter (g/dL) (>=80 grams per liter [g/L]).

  • Have an estimated glomerular filtration rate (creatinine-based Bedside Schwartzequation) >= 30 milliliters per minute (mL/min) /1.73 meter square (m^2).

  • Be a female of nonchildbearing potential. If a female of childbearing potential,have a negative serum human chorionic gonadotropin (hCG) or beta-human chorionicgonadotropin (β-hCG) pregnancy test at screening. Males, or nonpregnant,nonlactating females who are sexually active must agree to comply with theapplicable contraceptive requirements of this protocol during the study treatmentadministration period and for 90 days after the last dose of study treatment.

  • Have life expectancy of >= 8 weeks.

  • Be willing and have an understanding and ability to fully comply with the studyprocedures and restrictions defined in the protocol. For younger children, theparent/both parents or LAR must meet this criterion.

  • Participants must have a confirmed negative human immunodeficiency virus (HIV) testresult within 3 months of first dose of study drug or, if unavailable, be tested bya local laboratory during the screening period.

Exclusion

Exclusion Criteria:

  • Have CMV tissue invasive disease involving the central nervous system (CNS) orretina as assessed by the investigator at the time of screening.

  • Have uncontrolled other type of infection as assessed by the investigator on thedate of enrollment.

  • Have a history of clinically relevant alcohol or drug abuse that may interfere withtreatment compliance or assessments with the protocol as determined by theinvestigator.

  • Be receiving valganciclovir, ganciclovir, cidofovir, foscarnet, leflunomide,letermovir, or artesunate when study treatment is initiated, or anticipated torequire one of these agents during the 8-week treatment period.

  • Have a known hypersensitivity to maribavir or to any excipients.

  • Have severe vomiting, diarrhea, or other severe gastrointestinal (GI) illness within 24 hours prior to the first dose of study treatment or a GI absorption abnormalitythat would preclude administration of oral medication.

  • Require mechanical ventilation or vasopressors for hemodynamic support at baseline (Visit 2/Day 1/Week 0).

  • Be pregnant (or expecting to conceive) or nursing.

  • Have previously completed, discontinued, or have been withdrawn from this study.

  • Have received any investigational agent or device within 30 days before initiationof study treatment (includes CMV specific T-cells) or plan to receive aninvestigational agent or device during the study.

Previously approved agents under investigation for additional indications are not exclusionary.

  • Have previously received maribavir or CMV vaccine at any time.

  • Have any clinically significant medical or surgical condition that, in theinvestigator's opinion, could interfere with interpretation of study results,contraindicate the administration of the study treatment, or compromise the safetyor well-being of the participant.

  • Have severe liver disease (Child-Pugh score of >= 10).

  • Have serum aspartate aminotransferase greater than (>) 5 times upper limit of normal (ULN) at screening, or serum alanine aminotransferase > 5 times ULN at screening, ortotal bilirubin >= 3.0 times ULN at screening (except for documented Gilbert'ssyndrome), as analyzed by local laboratory.

  • Have positive results for HIV.

  • Have active malignancy with the exception of nonmelanoma skin cancer, as determinedby the investigator. Participants who experience relapse or progression of theirunderlying malignancy (for which HSCT or SOT was performed), as determined by theinvestigator, are not to be enrolled.

  • Be undergoing treatment for acute or chronic hepatitis B or hepatitis C.

  • Requiring ongoing treatment with or an anticipated need for treatment with a strongcytochrome P450 3A (CYP3A) inducer.

  • Have a low body weight where total blood volume (TBV) required during studyparticipation will exceed 1 percent (%) TBV per study visit or 3% TBV over a 4-weekperiod.

Study Design

Total Participants: 80
Treatment Group(s): 1
Primary Treatment: Maribavir
Phase: 3
Study Start date:
November 13, 2023
Estimated Completion Date:
January 18, 2027

Connect with a study center

  • Sydney Children's Hospital

    Randwick, New South Wales 2031
    Australia

    Site Not Available

  • Queensland Children's Hospital

    South Brisbane, Queensland 4101
    Australia

    Site Not Available

  • Queensland Children's Hospital

    Woollangabba, Queensland 4101
    Australia

    Site Not Available

  • Royal Children's Hospital Melbourne - PIN

    Parkville, Victoria 3052
    Australia

    Site Not Available

  • Perth Children's Hospital

    Nedlands, Western Australia 6009
    Australia

    Site Not Available

  • Hôpital Universitaire des Enfants Reine Fabiola (HUDERF)

    Bruxelles, Brussels 1020
    Belgium

    Site Not Available

  • Cliniques Universitaires Saint-Luc

    Sint-Lambrechts-Woluwe, Brussels 1200
    Belgium

    Site Not Available

  • UZ Gent

    Gent, Oost-Vlaanderen 9000
    Belgium

    Site Not Available

  • Hôpital Universitaire des Enfants Reine Fabiola

    Brussels, 1020
    Belgium

    Active - Recruiting

  • Hôpital Universitaire des Enfants Reine Fabiola (HUDERF)

    Brussels, 1020
    Belgium

    Site Not Available

  • Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo

    Porto Alegre, Rio Grande Do Sul 90160-093
    Brazil

    Site Not Available

  • Hospital de Clinicas de Porto Alegre (HCPA) - PPDS

    Porto Alegre, Rio Grande Do Sul 90035-903
    Brazil

    Site Not Available

  • Irmandade Da Santa Casa de Misericordia de Porto Alegre

    Porto Alegre, Rio Grande Do Sul 90020-090
    Brazil

    Site Not Available

  • Hospital Do Rim E Hipertensão

    Sao Paulo, 04038-002
    Brazil

    Site Not Available

  • Hospital Do Rim E Hipertensão

    São Paulo, 04038-002
    Brazil

    Site Not Available

  • Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo

    São Paulo, 05403-000
    Brazil

    Site Not Available

  • Beijing Children's Hospital, Capital Medical University - PIN

    Beijing, Beijing 100045
    China

    Site Not Available

  • Children's Hospital Capital Institute of Pediatrics

    Beijing, Beijing 100020
    China

    Site Not Available

  • Shanghai Children's Medical Center

    Shanghai, Shanghai 200127
    China

    Site Not Available

  • Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences - PPDS

    Tianjin, Tianjin 300020
    China

    Site Not Available

  • CHRU Rennes

    Rennes, Ille-et-Vilaine 35000
    France

    Active - Recruiting

  • CHU de Rennes - Hôpital Pontchaillou

    Rennes, Ille-et-Vilaine 35200
    France

    Site Not Available

  • CHU de Grenoble

    La Tronche, Isère 38700
    France

    Active - Recruiting

  • CHU de Grenoble Alpes - Hôpital Michallon

    La Tronche, Isère 38700
    France

    Site Not Available

  • CHRU Nantes

    Nantes, Loire-Atlantique 44000
    France

    Site Not Available

  • Hopital Necker

    Paris, 75015
    France

    Site Not Available

  • Universitätsklinikum Würzburg

    Würzburg, Bayern 97080
    Germany

    Site Not Available

  • Universitätsklinikum Münster

    Münster, Nordrhein-Westfalen 48149
    Germany

    Site Not Available

  • Universitatsklinikum Jena - Am Klinikum 1-Erlanger Allee 101

    Jena, Thüringen 07745
    Germany

    Site Not Available

  • Universitätsklinikum Hamburg Eppendorf

    Hamburg, 20246
    Germany

    Site Not Available

  • Medizinische Hochschule Hannover

    Hannover, 30625
    Germany

    Site Not Available

  • Sheba Medical Center - PPDS

    Ramat Gan, Tel-Aviv 52394
    Israel

    Active - Recruiting

  • The Chaim Sheba Medical Center - PPDS

    Ramat Gan, Tel-Aviv 52394
    Israel

    Site Not Available

  • Tel Aviv Sourasky Medical Center - PPDS

    Tel Aviv-Yafo, Tel-Aviv 64239
    Israel

    Active - Recruiting

  • Tel Aviv Sourasky Medical Center Ichilov - PPDS

    Tel Aviv-Yafo, Tel-Aviv 64239
    Israel

    Site Not Available

  • Rambam Health Care Campus - PPDS

    Haifa, 31096
    Israel

    Site Not Available

  • Rambam Medical Center - PPDS

    Haifa, 31096
    Israel

    Active - Recruiting

  • Hadassah Medical Center - PPDS

    Jerusalem, 911
    Israel

    Active - Recruiting

  • Hadassah Medical Center- Ein Kerem - PPDS

    Jerusalem, 911
    Israel

    Site Not Available

  • Hadassah Medical Center- Ein Kerem - PPDS

    Petah Tiqva, 4920235
    Israel

    Site Not Available

  • National Center for Child Health and Development

    Nagoya-Shi, Aiti 453-0046
    Japan

    Site Not Available

  • Saitama Children's Medical Center

    Isehara-Shi, Kanagawa 259-1143
    Japan

    Site Not Available

  • Shizuoka Children's Hospital

    Aoi-ku, Sizuoka 420-8660
    Japan

    Site Not Available

  • Osaka Women's and Children's Hospital

    Izumi-Shi, Ôsaka 594-1101
    Japan

    Site Not Available

  • Hyogo Prefectural Kobe Children's Hospital

    Chiba-Shi, 650-0047
    Japan

    Site Not Available

  • Hospital Sant Joan de Deu - PIN

    Espluges De Llobregat, Barcelona 08950
    Spain

    Site Not Available

  • Hospital Universitario La Paz - PPDS

    Horcajo de la Sierra, Madrid 28755
    Spain

    Site Not Available

  • Hospital Regional Universitario de Malaga - Hospital Materno-Infantil

    Malaga, Málaga 29011
    Spain

    Site Not Available

  • Hospital Sant Joan de Deu - PIN

    Barcelona, 08950
    Spain

    Site Not Available

  • Hospital Universitario Vall d´Hebron

    Barcelona, 08035
    Spain

    Site Not Available

  • Hospital Universitario Vall d´Hebron- PPDS

    Barcelona, 08035
    Spain

    Site Not Available

  • Hospital Infantil Universitario Niño Jesus - PIN

    Madrid, 28009
    Spain

    Site Not Available

  • Hospital Universitario La Paz - PPDS

    Madrid, 28046
    Spain

    Site Not Available

  • King's College Hospital

    London, Lambeth SE5 9RS
    United Kingdom

    Site Not Available

  • Royal Manchester Children's Hospital

    Manchester, Lancashire M13 9WL
    United Kingdom

    Site Not Available

  • Royal Manchester Children's Hospital - PIN

    Manchester, Lancashire M13 9WL
    United Kingdom

    Site Not Available

  • Nottingham University Hospitals NHS Trust

    Nottingham, Nottinghamshire NG5 1PB
    United Kingdom

    Site Not Available

  • Birmingham Women's and Children's NHS Foundation Trust

    Birmingham, West Midlands B4 6NH
    United Kingdom

    Site Not Available

  • Great Ormond Street Hospital

    London, WC1N 3JH
    United Kingdom

    Site Not Available

  • University of Nebraska Medical Center

    Omaha, Nebraska 68198-7680
    United States

    Site Not Available

  • University of Nebraska Medical Center -985400 Nebraska Medical Center

    Omaha, Nebraska 68114-4113
    United States

    Site Not Available

  • University of Nebraska Medical Center-985400 Nebraska Medical

    Omaha, Nebraska 68198-7680
    United States

    Active - Recruiting

  • Cincinnati Children's Hospital Medical Center - PIN

    Cincinnati, Ohio 45229-3026
    United States

    Site Not Available

  • Cook Children's Health Care System

    Fort Worth, Texas 76104-2733
    United States

    Site Not Available

  • University of Texas MD Anderson Cancer Center - 1515 Holcombe Blvd

    Houston, Texas 77030-4000
    United States

    Site Not Available

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