LET for the prevention of CMV infection/disease in pediatric HSCT recipients

JRCT ID: jRCT2080225146

Registered date:30/03/2020

Basic Information

• Recruitment status: completed
• Health condition(s) or Problem(s) studied: Pediatric participants receiving HSCT at risk for CMV infection and/or disease
• Date of first enrollment: 08/05/2020
• Target sample size: 5
• Countries of recruitment: United States,Turkiye,Spain,Poland,Mexico,Israel,Germany,France,Colombia,Australia
• Study type: Interventional
• Intervention(s): Receive LET once a day from the day of enrollment (Day 1, within 28 days post-transplant) through 14 weeks (~100 days) post-transplant

Outcome(s)

• Primary Outcome: AUC0-24, Cmax (for participants receiving oral formulation), Ceoi (for participants receiving IV formulation), and Ctrough

Secondary Outcome

Adverse Events (AEs)
AEs Resulting in Study Medication
Discontinuation
Clinically significant CMV infection through Week 14 (~100 days) post-transplant and through Week 24 (~6 months) post-transplant
Score on a palatability scale.

Key inclusion & exclusion criteria

• Age minimum: >=
• Age maximum: < 18age old
• Gender: Both

Include criteria

- All participants 12 to <18 years old must have documented positive CMV serostatus(CMV IgG seropositive)for the recipient(R+)within 90 days prior to enrollment. Participants from birth to <12 years old must have documented positive CMV serostatus(CMV IgG seropositive)for the recipient(R+)within 90 days prior to enrollment and/or the donor(D+); the donor serostatus should be documented within 1 year prior to enrollment.
- Is the recipient of a first allogeneic HSCT(bone marrow, peripheral blood stem cell, or cord blood transplant).
- Has undetectable CMV DNA from a plasma or whole blood sample collected within 5 days prior to enrollment.
- Is within 28 days post-HSCT at the time of enrollment.
- Females are not pregnant, not breastfeeding, and is not a woman of childbearing potential(WOCBP); or is a WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 28 days after the last dose of study intervention.
- Participants from 2 to <18 years of age must not be on concomitant Cyclosporin A(CsA), and must be able to take LET tablets or the oral granules(either by mouth or via G tube/NG tube), provided the participant does not have a condition that may interfere with the absorption of oral medication(e.g. vomiting, diarrhea, or a malabsorptive condition)from the day of enrollment until the intensive PK sampling is completed in these participants.
- For participants 2 <12 years old their weight should be at least 10 kg; for participants from birth to <2 years old their weight should be at least 2.5 kg and less than or equal to 15 kg at the time of enrollment.

Exclude criteria

- Has received a previous allogeneic HSCT(Note: receipt of a previous autologous HSCT is acceptable).
- Has a history of CMV end-organ disease within 6 months prior to enrollment.
- Has evidence of CMV viremia at any time from either signing of the ICF or the HSCT procedure, whichever is earlier, until the time of enrollment.
- Has suspected or known hypersensitivity to active or inactive ingredients of LET formulations.
- Has severe hepatic insufficiency within 5 days prior to enrollment.
- Is a)on renal replacement therapy(eg, hemodialysis, peritoneal dialysis)OR b)has end-stage renal impairment.
- Has both moderate hepatic insufficiency and moderate-to-severe renal insufficiency.
- Has an uncontrolled infection on the day of enrollment.
- Requires mechanical ventilation or is hemodynamically unstable at the time of enrollment.
- Has a documented positive result for a human immunodeficiency virus antibody(HIVAb)test at any time prior to enrollment, or for hepatitis C virus antibody(HCV-Ab)with detectable HCV RNA, or hepatitis B surface antigen(HBsAg)within 90 days prior to enrollment.
- Has active solid tumor malignancies with the exception of localized basal cell or squamous cell skin cancer or the condition under treatment(e.g. lymphomas).
- Has a preexisting cardiac condition a)for which the patient is currently being treated or b)which required hospitalization within the last 6 months or c)that may be expected to recur during the course of the trial.
- Has received within 7 days prior to screening any of the following: ganciclovir; valganciclovir; foscarnet; acyclovir; valacyclovir; famciclovir.
- Has received within 30 days prior to screening of any of the following: cidofovir; CMV immunoglobulin; any investigational CMV antiviral agent/biologic therapy; Rifampin and other strong inducers(such as phenytoin, carbamazepine, St John's wort(Hypericum perforatum), rifabutin and phenobarbital)and moderate inducers such as nafcillin, thioridazine, modafinil and bosentan.
- Has received LET at any time prior to enrollment in this study.
- Is currently participating or has participated in a study with an unapproved investigational compound or device within 28 days, or 5X half-life of the investigational compound(excluding monoclonal antibodies), whichever is longer, of initial dosing in this study.
- Has previously participated in this study or any other study involving LET.
- Has previously participated or is currently participating in any study involving administration of a CMV vaccine or another CMV investigational agent, or is planning to participate in a study of a CMV vaccine or another CMV investigational agent during the course of this study.
- Is pregnant or expecting to conceive, is breastfeeding, or plans to breastfeed from the time of consent through 28 days after the last dose of study intervention.
- Is expecting to donate eggs starting from the time of consent through 28 days after the last dose of study intervention.
- Has clinically relevant drug or alcohol abuse within 12 months of screening that may interfere with participant treatment, assessment, or compliance with the protocol, as assessed by the investigator.

Related Information

• Primary Sponsor: MSD K.K.
• Secondary ID(s): NCT03940586,JapicCTI-205242