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Trial record 7 of 12 for:    CMV | Berlin, Germany

Letermovir Treatment in Pediatric Participants Following Allogeneic Haematopoietic Stem Cell Transplantation (HSCT) (MK-8228-030)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03940586
Recruitment Status : Recruiting
First Posted : May 7, 2019
Last Update Posted : June 23, 2022
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme LLC

Tracking Information
First Submitted Date  ICMJE May 6, 2019
First Posted Date  ICMJE May 7, 2019
Last Update Posted Date June 23, 2022
Actual Study Start Date  ICMJE August 8, 2019
Estimated Primary Completion Date February 21, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 6, 2019)
  • Area under the concentration-time curve of plasma letermovir for oral formulation [ Time Frame: Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose ]
    Area under the curve from time 0 to 24 hours post-dose (AUC0-24) of plasma letermovir during intensive pharmacokinetics (PK), for participants receiving oral formulation.
  • Maximal concentration of plasma letermovir for oral formulation [ Time Frame: Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose ]
    Maximal concentration (Cmax) of plasma letermovir during intensive PK, for participants receiving oral formulation.
  • Minimum concentration of plasma letermovir observed before next dose for oral formulation [ Time Frame: Day 7: Pre-dose ]
    Minimum concentration of plasma letermovir observed before next dose (Ctrough) during intensive PK, for participants receiving oral formulation.
  • Area under the concentration-time curve of plasma letermovir for intravenous formulation [ Time Frame: After 5 consecutive days of administration of intravenous formulation: Pre-dose, 1, 2.5, 8, and 24 hours post-dose (up to 14 weeks) ]
    Area under the curve from time 0 to 24 hours post-dose (AUC0-24) of plasma letermovir, for participants receiving intravenous (IV) formulation.
  • Concentration at the end of infusion of plasma letermovir for IV formulation [ Time Frame: After 5 consecutive days of administration of IV formulation: 1 hour post-dose (up to 14 weeks) ]
    Concentration of plasma letermovir at the end of infusion (Ceoi), for participants receiving IV formulation.
  • Minimum concentration of plasma letermovir observed before next dose for IV formulation [ Time Frame: After 5 consecutive days of administration of IV formulation: Pre-dose (up to 14 weeks) ]
    Minimum concentration of plasma letermovir observed before next dose (Ctrough) during intensive PK, for participants receiving IV formulation.
  • Minimum concentration of plasma letermovir observed before next dose during sparse PK for oral formulation [ Time Frame: Pre-dose on Weeks 2, 4, 6, 8, 12, 14 ]
    Minimum concentration of plasma letermovir observed before next dose (Ctrough) during sparse PK, for participants receiving oral formulation.
  • Minimum concentration of plasma letermovir observed before next dose during sparse PK for IV formulation [ Time Frame: Pre-dose on Weeks 2, 4, 6, 8, 12, 14 ]
    Minimum concentration of plasma letermovir observed before next dose (Ctrough) during sparse PK, for participants receiving IV formulation.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 6, 2019)
  • Participants with an adverse event [ Time Frame: Up to Week 48 post-transplant (up to 52 weeks) ]
    Percentage of participants with one or more adverse event (AE).
  • Participants who discontinued study medication [ Time Frame: Up to Week 14 post-transplant (up to 18 weeks) ]
    Percentage of participants who discontinued study medication due to an AE.
  • Participants with clinically significant CMV infection through Week 14 post-transplant [ Time Frame: Up to Week 14 post-transplant (up to 18 weeks) ]
    Percentage of participants with clinically significant CMV infection (CS-CMVi) through Week 14 post-transplant
  • Participants with clinically significant CMV infection through Week 24 post-transplant [ Time Frame: Up to Week 24 post-transplant (up to 28 weeks) ]
    Percentage of participants with clinically significant CMV infection (CS-CMVi) through Week 24 post-transplant
  • Score on a palatability scale for participants receiving oral granules. [ Time Frame: On the first and eighth day of administration of oral formulation up to Week 14 post-transplant (up to 18 weeks) ]
    Palatability was measured by a facial hedonic scale (FHS), a five point facial expression scale depicting various degrees of pleasure, where a score of 1 indicated disliked very much; ranging to a score of 5 which indicated liked very much.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Letermovir Treatment in Pediatric Participants Following Allogeneic Haematopoietic Stem Cell Transplantation (HSCT) (MK-8228-030)
Official Title  ICMJE A Phase 2b Open-label, Single-arm Study to Evaluate Pharmacokinetics, Efficacy, Safety and Tolerability of Letermovir in Pediatric Participants From Birth to Less Than 18 Years of Age at Risk of Developing CMV Infection and/or Disease Following Allogeneic Haematopoietic Stem Cell Transplantation (HSCT)
Brief Summary The primary objective of this study is to evaluate the pharmacokinetics (PK) of letermovir (LET) in pediatric participants. Participants will be enrolled in the following 3 age groups: Age Group 1: From 12 to <18 years of age (adolescents); Age Group 2: From 2 to <12 years of age (children); and Age Group 3: From birth to <2 years of age (neonates, infants and toddlers). All participants will receive open label LET for 14 weeks (~100 days) post-transplant, with doses based on body weight and age.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE Cytomegalovirus (CMV) Infection
Intervention  ICMJE
  • Drug: Letermovir oral granules
    Granules administered orally based on age, weight, and whether participant takes cyclosporin A as a concomitant medication.
    Other Names:
    • MK-8228
    • AIC246
    • AIC001
  • Drug: Letermovir tablet
    Tablet administered orally based on age, weight, and whether participant takes cyclosporin A as a concomitant medication.
    Other Names:
    • MK-8228
    • AIC246
    • AIC001
  • Drug: Letermovir intravenous
    Letermovir administered intravenously based on age, weight, and whether participant takes cyclosporin A as a concomitant medication.
    Other Names:
    • MK-8228
    • AIC246
    • AIC001
Study Arms  ICMJE Experimental: Letermovir
Letermovir administered either orally or intravenously within 28 days post-transplant, once daily through week 14 (approximately 100 days). Dosing will vary based on age, weight, and whether participant takes cyclosporin A as a concomitant medication.
Interventions:
  • Drug: Letermovir oral granules
  • Drug: Letermovir tablet
  • Drug: Letermovir intravenous
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 6, 2019)
60
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 18, 2023
Estimated Primary Completion Date February 21, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion 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.

Exclusion 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 17 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Toll Free Number 1-888-577-8839 Trialsites@merck.com
Listed Location Countries  ICMJE Germany,   Australia,   Colombia,   France,   Israel,   Japan,   Mexico,   Poland,   Spain,   Turkey,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03940586
Other Study ID Numbers  ICMJE 8228-030
MK-8228-030 ( Other Identifier: Merck Protocol Number )
205242 ( Registry Identifier: JAPIC-CTI )
2018-001326-25 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php
Current Responsible Party Merck Sharp & Dohme LLC
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Merck Sharp & Dohme LLC
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Merck Sharp & Dohme LLC
PRS Account Merck Sharp & Dohme LLC
Verification Date June 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP