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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05319353




Registration number
NCT05319353
Ethics application status
Date submitted
1/04/2022
Date registered
8/04/2022
Date last updated
28/06/2024

Titles & IDs
Public title
A Study to Evaluate the Safety and Tolerability, Pharmacokinetics, and Antiviral Activity of Maribavir for the Treatment of Children and Teenage Transplant Recipients With CMV Infection
Scientific title
A Phase 3, Open-label, Single-arm, Repeated-dose 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)
Secondary ID [1] 0 0
2021-004279-15
Secondary ID [2] 0 0
TAK-620-2004
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cytomegalovirus (CMV) 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Infection 0 0 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Maribavir

Experimental: Cohort 1: Maribavir 400 or 200 mg - Participants with greater than or equal to (\>=) 12 to less than (\<) 18 years of age will receive maribavir 400 milligrams (mg) (2\*200 mg tablets) twice daily (BID) based on body weight \>= 25 kilogram (kg) or 200 mg tablet BID based on body weight 10 to \< 25 kg orally for up to 8 weeks treatment period (Day 0/Week 0 to Day 56/Week 8). The dosing regimen will be based on the participant's body weight and may be updated over the course of the study based on the internal interim analyses on PK, safety, and tolerability of at least 5 participants in each cohort.

Experimental: Cohort 2: Maribavir 400 or 200 mg - Participants with \>= 6 to \< 12 years of age will receive maribavir 400 mg (2\*200 mg tablets) BID based on body weight \>= 25 kg or 200 mg tablet BID based on body weight 10 to \< 25 kg orally for up to 8 weeks treatment period (Day 0/Week 0 to Day 56/Week 8). The dosing regimen will be based on the participant's body weight and may be updated over the course of the study based on the internal interim analyses on PK, safety, and tolerability of at least 5 participants in each cohort.

Experimental: Cohort 3: Maribavir - Participants with 0 to \< 6 years of age will receive maribavir based on PK modeling.


Treatment: Drugs: Maribavir
Participants will receive maribavir.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Maximum Observed Plasma Concentration (Cmax) of Maribavir
Timepoint [1] 0 0
Pre-dose, 0.5, 1.5, 3, 4, 6, and 8 hours post-dose on Day 7 (Week 1)
Primary outcome [2] 0 0
Time to Maximum Observed Concentration (Tmax) of Maribavir
Timepoint [2] 0 0
Pre-dose, 0.5, 1.5, 3, 4, 6, and 8 hours post-dose on Day 7 (Week 1)
Primary outcome [3] 0 0
Minimum Plasma Concentration (Cmin) of Maribavir
Timepoint [3] 0 0
Pre-dose, 0.5, 1.5, 3, 4, 6, and 8 hours post-dose on Day 7 (Week 1); Pre-dose on Day 28 (Week 4); Pre-dose and 2 to 4 hours post-dose on Day 56 (Week 8)
Primary outcome [4] 0 0
Area Under the Plasma Concentration-Time Curve Over the 1 Dosing Interval of 12 Hours at Steady State (AUC0-tau) of Maribavir
Timepoint [4] 0 0
Pre-dose, 0.5, 1.5, 3, 4, 6, and 8 hours post-dose on Day 7 (Week 1)
Primary outcome [5] 0 0
Half-Life (t1/2) of Maribavir
Timepoint [5] 0 0
Pre-dose, 0.5, 1.5, 3, 4, 6, and 8 hours post-dose on Day 7 (Week 1)
Primary outcome [6] 0 0
Terminal Elimination Rate Constant (lambdaz) of Maribavir
Timepoint [6] 0 0
Pre-dose, 0.5, 1.5, 3, 4, 6, and 8 hours post-dose on Day 7 (Week 1)
Primary outcome [7] 0 0
Apparent Volume of Distribution (Vz/F) of Maribavir
Timepoint [7] 0 0
Pre-dose, 0.5, 1.5, 3, 4, 6, and 8 hours post-dose on Day 7 (Week 1)
Primary outcome [8] 0 0
Apparent Oral Clearance (CL/F) of Maribavir
Timepoint [8] 0 0
Pre-dose, 0.5, 1.5, 3, 4, 6, and 8 hours post-dose on Day 7 (Week 1)
Primary outcome [9] 0 0
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
Timepoint [9] 0 0
From start of study drug administration up to follow-up (Week 20)
Secondary outcome [1] 0 0
Percentage of Participants With Confirmed CMV viremia Clearance at Week 8
Timepoint [1] 0 0
At Week 8
Secondary outcome [2] 0 0
Percentage of Participants who Achieve Maintenance of Confirmed CMV Viremia Clearance and Symptom Control at Week 8 Through Weeks 12, 16 and 20
Timepoint [2] 0 0
At Week 8 through Weeks 12, 16, and 20
Secondary outcome [3] 0 0
Percentage of Participants With Confirmed Recurrence of CMV Viremia on Study Treatment and Off Study Treatment
Timepoint [3] 0 0
Up to Week 20
Secondary outcome [4] 0 0
Time to First Confirmed Viremia Clearance
Timepoint [4] 0 0
Up to Week 20
Secondary outcome [5] 0 0
Percentage of Participants With Confirmed Recurrence of CMV Viremia Treated With Alternative Anti-CMV Treatment During 12-Week Follow-up Period in Participants With Confirmed Viremia Clearance at Week 8
Timepoint [5] 0 0
From Week 8 through Week 20
Secondary outcome [6] 0 0
Change From Baseline in Log10 Plasma CMV Deoxyribonucleic Acid (DNA) Load
Timepoint [6] 0 0
Baseline up to Week 20
Secondary outcome [7] 0 0
Number of Participants who Develop CMV Resistance to Maribavir
Timepoint [7] 0 0
Up to Week 12
Secondary outcome [8] 0 0
Summary Scores for Palatability Assessment of Maribavir
Timepoint [8] 0 0
At Weeks 1, 4, and 8

Eligibility
Key inclusion criteria
* Parent/both parents or legally authorized representative (LAR) must provide signature of informed consent and there must be documentation of assent by the participant, as age appropriate, 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 capabilities or an electronic face-to-face consent interview when these individuals are unable to travel to the site.
* Be a male or female child or adolescent < 18 years of age at the time of consent. For participants in Cohort 3 only, must have a gestational age of at least 38 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, with a CMV deoxyribonucleic acid (DNA) screening value of >= 1365 International Units per milliliter (IU/mL) in whole blood or >= 455 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 must be taken within 14 days of first dose of study drug, with the second sample obtained within 5 days prior to first dose of study drug. The same laboratory and same sample type (whole blood or plasma) must be used for both assessments.
* 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)
* Have an estimated glomerular filtration rate (creatinine-based Bedside Schwartz equation) >= 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 chorionic gonadotropin (ß-hCG) pregnancy test at screening. Males, or nonpregnant, nonlactating females who are sexually active must agree to comply with the applicable contraceptive requirements of this protocol during the study treatment administration 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 study procedures and restrictions defined in the protocol. For younger children, the parent/both parents or LAR must meet this criterion.
Minimum age
No limit
Maximum age
17 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Have CMV tissue invasive disease involving the central nervous system (CNS) or retina as assessed by the investigator at the time of screening.
* Have uncontrolled other type of infection as assessed by the investigator on the date of enrollment.
* Have a history of clinically relevant alcohol or drug abuse that may interfere with treatment compliance or assessments with the protocol as determined by the investigator.
* Be receiving valganciclovir, ganciclovir, cidofovir, foscarnet, leflunomide, letermovir, or artesunate when study treatment is initiated, or anticipated to require 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 abnormality that would preclude administration of oral medication.
* Require mechanical ventilation or vasopressors for hemodynamic support at baseline (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 initiation of study treatment (includes CMV specific T-cells). 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 the investigator's opinion, could interfere with interpretation of study results, contraindicate the administration of the study treatment, or compromise the safety or 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, or total bilirubin >= 3.0 times ULN at screening (except for documented Gilbert's syndrome), as analyzed by local laboratory.
* Have 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 or SOT was performed), as determined by the investigator, 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 strong cytochrome P450 3A (CYP3A) inducer.
* Have a low body weight where total blood volume (TBV) required during study participation will exceed 1 percent (%) TBV per study visit or 3% TBV over 30-day period.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
13/11/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
22/11/2026
Actual
Sample size
Target
80
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 0 0
Perth Children's Hospital - Nedlands
Recruitment postcode(s) [1] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Nebraska
Country [2] 0 0
United States of America
State/province [2] 0 0
Texas
Country [3] 0 0
Belgium
State/province [3] 0 0
Brussels
Country [4] 0 0
Belgium
State/province [4] 0 0
Oost-Vlaanderen
Country [5] 0 0
Brazil
State/province [5] 0 0
Rio Grande Do Sul
Country [6] 0 0
Brazil
State/province [6] 0 0
Sao Paulo
Country [7] 0 0
China
State/province [7] 0 0
Beijing
Country [8] 0 0
China
State/province [8] 0 0
Shanghai
Country [9] 0 0
China
State/province [9] 0 0
Tianjin
Country [10] 0 0
France
State/province [10] 0 0
Ille-et-Vilaine
Country [11] 0 0
France
State/province [11] 0 0
Isère
Country [12] 0 0
France
State/province [12] 0 0
Loire-Atlantique
Country [13] 0 0
France
State/province [13] 0 0
Paris
Country [14] 0 0
Germany
State/province [14] 0 0
Bayern
Country [15] 0 0
Germany
State/province [15] 0 0
Niedersachsen
Country [16] 0 0
Germany
State/province [16] 0 0
Nordrhein-Westfalen
Country [17] 0 0
Germany
State/province [17] 0 0
Thüringen
Country [18] 0 0
Germany
State/province [18] 0 0
Hamburg
Country [19] 0 0
Israel
State/province [19] 0 0
Tel-Aviv
Country [20] 0 0
Israel
State/province [20] 0 0
Haifa
Country [21] 0 0
Israel
State/province [21] 0 0
Jerusalem
Country [22] 0 0
Japan
State/province [22] 0 0
Kanagawa
Country [23] 0 0
Japan
State/province [23] 0 0
Aoi-ku
Country [24] 0 0
Japan
State/province [24] 0 0
Chiba-Shi
Country [25] 0 0
Japan
State/province [25] 0 0
Nagoya-Shi
Country [26] 0 0
Spain
State/province [26] 0 0
Barcelona
Country [27] 0 0
Spain
State/province [27] 0 0
Málaga
Country [28] 0 0
Spain
State/province [28] 0 0
Madrid
Country [29] 0 0
United Kingdom
State/province [29] 0 0
Lancashire
Country [30] 0 0
United Kingdom
State/province [30] 0 0
Nottinghamshire
Country [31] 0 0
United Kingdom
State/province [31] 0 0
West Midlands

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Takeda
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Takeda Development Center Americas, Inc.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief 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) adult tablet formulation or other formulation based on PK modeling.

The participants will be treated with maribavir for 8 weeks.

Participants need to visit their doctor during 12-week follow-up period.
Trial website
https://clinicaltrials.gov/study/NCT05319353
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Study Director
Address 0 0
Takeda
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Takeda Contact
Address 0 0
Country 0 0
Phone 0 0
+1-877-825-3327
Fax 0 0
Email 0 0
medinfoUS@takeda.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05319353