Clinical Trial Results:
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)
Summary
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EudraCT number |
2018-001326-25 |
Trial protocol |
DE ES Outside EU/EEA FR PL |
Global end of trial date |
25 Aug 2023
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Results information
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Results version number |
v1(current) |
This version publication date |
15 Feb 2024
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First version publication date |
15 Feb 2024
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
8228-030
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03940586 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Merck Sharp & Dohme LLC
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Sponsor organisation address |
126 East Lincoln Avenue, Rahway, NJ, United States, P.O. Box 2000
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Public contact |
Clinical Trials Disclosure, Merck Sharp & Dohme LLC, ClinicalTrialsDisclosure@merck.com
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Scientific contact |
Clinical Trials Disclosure, Merck Sharp & Dohme LLC, ClinicalTrialsDisclosure@merck.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
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EMA paediatric investigation plan number(s) |
EMEA-001631-PIP01-14 | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Interim
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Date of interim/final analysis |
04 Jan 2023
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
04 Jan 2023
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Global end of trial reached? |
Yes
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Global end of trial date |
25 Aug 2023
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary objective of this study was to evaluate the pharmacokinetics (PK) of letermovir (LET) in pediatric participants. Participants were 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 received open label LET for 14 weeks (~100 days) post-transplant, with doses based on body weight and age.
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Protection of trial subjects |
This study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
08 Aug 2019
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Australia: 7
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Country: Number of subjects enrolled |
Colombia: 6
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Country: Number of subjects enrolled |
France: 2
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Country: Number of subjects enrolled |
Germany: 8
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Country: Number of subjects enrolled |
Israel: 9
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Country: Number of subjects enrolled |
Japan: 5
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Country: Number of subjects enrolled |
Mexico: 2
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Country: Number of subjects enrolled |
Poland: 5
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Country: Number of subjects enrolled |
Spain: 4
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Country: Number of subjects enrolled |
Türkiye: 6
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Country: Number of subjects enrolled |
United States: 11
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Worldwide total number of subjects |
65
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EEA total number of subjects |
19
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
8
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Children (2-11 years) |
29
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Adolescents (12-17 years) |
28
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||||||||||||||||||||
Pre-assignment
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Screening details |
Male and female recipients of a first allogeneic hematopoietic stem cell transplant (HSCT), between the ages of birth and <18 years of age, who were at risk for cytomegalovirus (CMV) infection and/or disease, and who had undetectable CMV deoxyribonucleic acid (DNA) collected within 5 days before enrollment. were enrolled in this study. | ||||||||||||||||||||||||||||
Period 1
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Period 1 title |
Randomized
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Is this the baseline period? |
No | ||||||||||||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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12 - <18 Years | ||||||||||||||||||||||||||||
Arm description |
Letermovir (LET) 480 mg without cyclosporin (CsA), or 240 mg with CsA, administered either orally as tablets or in granular form, or by intravenous (IV) infusion, once daily (QD) through week 14 (~ 100 days) post-transplant. | ||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||
Investigational medicinal product name |
Letermovir oral granules
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Investigational medicinal product code |
|||||||||||||||||||||||||||||
Other name |
MK-8228
AIC246
AIC001
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Pharmaceutical forms |
Granules
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Routes of administration |
Oral use
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Dosage and administration details |
Granules administered orally based on age, weight, and whether participant takes cyclosporin A as a concomitant medication.
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Investigational medicinal product name |
Letermovir intravenous
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Investigational medicinal product code |
|||||||||||||||||||||||||||||
Other name |
MK-8228 AIC246 AIC001
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Pharmaceutical forms |
Solution for injection/infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Letermovir administered intravenously based on age, weight, and whether participant takes cyclosporin A as a concomitant medication.
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Investigational medicinal product name |
Letermovir tablet
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Investigational medicinal product code |
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Other name |
MK-8228
AIC246
AIC001
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Tablet administered orally based on age, weight, and whether participant takes cyclosporin A as a concomitant medication.
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Arm title
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2 - <12 Years | ||||||||||||||||||||||||||||
Arm description |
Participants ≥30 kg body weight (BW): LET 480 mg orally without CsA, or 240 mg with CsA, in granular form, or 240 mg IV with or without CsA; 18 to <30 kg BW: LET 240 mg orally without CsA, or 120 mg with CsA, either in granular form, or 120 mg IV with or without CsA; 10 to <18 kg BW: LET 120 mg orally without CsA, or 60 mg with CsA, in granular form, or 60 mg IV with or without CsA, all QD through week 14 (~ 100 days) post-transplant. | ||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||
Investigational medicinal product name |
Letermovir intravenous
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Investigational medicinal product code |
|||||||||||||||||||||||||||||
Other name |
MK-8228 AIC246 AIC001
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Pharmaceutical forms |
Solution for injection/infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Letermovir administered intravenously based on age, weight, and whether participant takes cyclosporin A as a concomitant medication.
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Investigational medicinal product name |
Letermovir oral granules
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Investigational medicinal product code |
|||||||||||||||||||||||||||||
Other name |
MK-8228
AIC246
AIC001
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Pharmaceutical forms |
Granules
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Routes of administration |
Oral use
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Dosage and administration details |
Granules administered orally based on age, weight, and whether participant takes cyclosporin A as a concomitant medication.
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Arm title
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Birth - <2 Years | ||||||||||||||||||||||||||||
Arm description |
10 to ≤15 kg BW: LET 120 mg orally without CsA, or 60 mg with CsA, in granular form, or 60 mg IV with or without CsA; 7.5 to <10 kg BW: LET 80 mg orally without CsA, or 40 mg with CsA, either in granular form, or 40 mg IV with or without CsA; 5.0 to <7.5 kg BW: LET 40 mg orally without CsA, or 20 mg with CsA, in granular form, or 20 mg IV with or without CsA; 2.5 to <5.0 kg BW: LET 20 mg orally without CsA, or 10 mg with CsA, in granular form, or 10 mg IV with or without CsA, all QD through week 14 (~ 100 days) post-transplant. | ||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||
Investigational medicinal product name |
Letermovir intravenous
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Investigational medicinal product code |
|||||||||||||||||||||||||||||
Other name |
MK-8228 AIC246 AIC001
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Pharmaceutical forms |
Solution for injection/infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Letermovir administered intravenously based on age, weight, and whether participant takes cyclosporin A as a concomitant medication.
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Investigational medicinal product name |
Letermovir oral granules
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Investigational medicinal product code |
|||||||||||||||||||||||||||||
Other name |
MK-8228
AIC246
AIC001
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Pharmaceutical forms |
Granules
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Routes of administration |
Oral use
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Dosage and administration details |
Granules administered orally based on age, weight, and whether participant takes cyclosporin A as a concomitant medication.
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Period 2
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Period 2 title |
Treated
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Is this the baseline period? |
Yes [1] | ||||||||||||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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12 - <18 Years | ||||||||||||||||||||||||||||
Arm description |
Letermovir (LET) 480 mg without cyclosporin (CsA), or 240 mg with CsA, administered either orally as tablets or in granular form, or by intravenous (IV) infusion, once daily (QD) through week 14 (~ 100 days) post-transplant. | ||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||
Investigational medicinal product name |
Letermovir oral granules
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||||||||||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||||||||||
Other name |
MK-8228
AIC246
AIC001
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||||||||||||||||||||||||||||
Pharmaceutical forms |
Granules
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||||||||||||||||||||||||||||
Routes of administration |
Oral use
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Dosage and administration details |
Granules administered orally based on age, weight, and whether participant takes cyclosporin A as a concomitant medication.
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Investigational medicinal product name |
Letermovir intravenous
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||||||||||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||||||||||
Other name |
MK-8228 AIC246 AIC001
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Pharmaceutical forms |
Solution for injection/infusion
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||||||||||||||||||||||||||||
Routes of administration |
Intravenous use
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||||||||||||||||||||||||||||
Dosage and administration details |
Letermovir administered intravenously based on age, weight, and whether participant takes cyclosporin A as a concomitant medication.
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Investigational medicinal product name |
Letermovir tablet
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Investigational medicinal product code |
|||||||||||||||||||||||||||||
Other name |
MK-8228
AIC246
AIC001
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Tablet administered orally based on age, weight, and whether participant takes cyclosporin A as a concomitant medication.
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Arm title
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2 - <12 Years | ||||||||||||||||||||||||||||
Arm description |
Participants ≥30 kg body weight (BW): LET 480 mg orally without CsA, or 240 mg with CsA, in granular form, or 240 mg IV with or without CsA; 18 to <30 kg BW: LET 240 mg orally without CsA, or 120 mg with CsA, either in granular form, or 120 mg IV with or without CsA; 10 to <18 kg BW: LET 120 mg orally without CsA, or 60 mg with CsA, in granular form, or 60 mg IV with or without CsA, all QD through week 14 (~ 100 days) post-transplant. | ||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||
Investigational medicinal product name |
Letermovir intravenous
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Investigational medicinal product code |
|||||||||||||||||||||||||||||
Other name |
MK-8228 AIC246 AIC001
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Pharmaceutical forms |
Solution for injection/infusion
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||||||||||||||||||||||||||||
Routes of administration |
Intravenous use
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Dosage and administration details |
Letermovir administered intravenously based on age, weight, and whether participant takes cyclosporin A as a concomitant medication.
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Investigational medicinal product name |
Letermovir oral granules
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Investigational medicinal product code |
|||||||||||||||||||||||||||||
Other name |
MK-8228
AIC246
AIC001
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Pharmaceutical forms |
Granules
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Routes of administration |
Oral use
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Dosage and administration details |
Granules administered orally based on age, weight, and whether participant takes cyclosporin A as a concomitant medication.
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Arm title
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Birth - <2 Years | ||||||||||||||||||||||||||||
Arm description |
10 to ≤15 kg BW: LET 120 mg orally without CsA, or 60 mg with CsA, in granular form, or 60 mg IV with or without CsA; 7.5 to <10 kg BW: LET 80 mg orally without CsA, or 40 mg with CsA, either in granular form, or 40 mg IV with or without CsA; 5.0 to <7.5 kg BW: LET 40 mg orally without CsA, or 20 mg with CsA, in granular form, or 20 mg IV with or without CsA; 2.5 to <5.0 kg BW: LET 20 mg orally without CsA, or 10 mg with CsA, in granular form, or 10 mg IV with or without CsA, all QD through week 14 (~ 100 days) post-transplant. | ||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||
Investigational medicinal product name |
Letermovir oral granules
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||||||||||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||||||||||
Other name |
MK-8228
AIC246
AIC001
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||||||||||||||||||||||||||||
Pharmaceutical forms |
Granules
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||||||||||||||||||||||||||||
Routes of administration |
Oral use
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||||||||||||||||||||||||||||
Dosage and administration details |
Granules administered orally based on age, weight, and whether participant takes cyclosporin A as a concomitant medication.
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||||||||||||||||||||||||||||
Investigational medicinal product name |
Letermovir intravenous
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||||||||||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||||||||||
Other name |
MK-8228 AIC246 AIC001
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||||||||||||||||||||||||||||
Pharmaceutical forms |
Solution for injection/infusion
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||||||||||||||||||||||||||||
Routes of administration |
Intravenous use
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||||||||||||||||||||||||||||
Dosage and administration details |
Letermovir administered intravenously based on age, weight, and whether participant takes cyclosporin A as a concomitant medication.
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Notes [1] - Period 1 is not the baseline period. It is expected that period 1 will be the baseline period. Justification: Period 1, the number of participants randomized, is not the baseline period. Rather Period 2, the number of participants treated is the baseline period. |
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Notes [2] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: The number of participants reported to in the baseline period are not the same as the worldwide number enrolled in the trial because the number of participants in the baseline period are instead the number of participants treated. |
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Baseline characteristics reporting groups
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Reporting group title |
12 - <18 Years
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Reporting group description |
Letermovir (LET) 480 mg without cyclosporin (CsA), or 240 mg with CsA, administered either orally as tablets or in granular form, or by intravenous (IV) infusion, once daily (QD) through week 14 (~ 100 days) post-transplant. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
2 - <12 Years
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Reporting group description |
Participants ≥30 kg body weight (BW): LET 480 mg orally without CsA, or 240 mg with CsA, in granular form, or 240 mg IV with or without CsA; 18 to <30 kg BW: LET 240 mg orally without CsA, or 120 mg with CsA, either in granular form, or 120 mg IV with or without CsA; 10 to <18 kg BW: LET 120 mg orally without CsA, or 60 mg with CsA, in granular form, or 60 mg IV with or without CsA, all QD through week 14 (~ 100 days) post-transplant. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Birth - <2 Years
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Reporting group description |
10 to ≤15 kg BW: LET 120 mg orally without CsA, or 60 mg with CsA, in granular form, or 60 mg IV with or without CsA; 7.5 to <10 kg BW: LET 80 mg orally without CsA, or 40 mg with CsA, either in granular form, or 40 mg IV with or without CsA; 5.0 to <7.5 kg BW: LET 40 mg orally without CsA, or 20 mg with CsA, in granular form, or 20 mg IV with or without CsA; 2.5 to <5.0 kg BW: LET 20 mg orally without CsA, or 10 mg with CsA, in granular form, or 10 mg IV with or without CsA, all QD through week 14 (~ 100 days) post-transplant. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
12 - <18 Years
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Reporting group description |
Letermovir (LET) 480 mg without cyclosporin (CsA), or 240 mg with CsA, administered either orally as tablets or in granular form, or by intravenous (IV) infusion, once daily (QD) through week 14 (~ 100 days) post-transplant. | ||
Reporting group title |
2 - <12 Years
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Reporting group description |
Participants ≥30 kg body weight (BW): LET 480 mg orally without CsA, or 240 mg with CsA, in granular form, or 240 mg IV with or without CsA; 18 to <30 kg BW: LET 240 mg orally without CsA, or 120 mg with CsA, either in granular form, or 120 mg IV with or without CsA; 10 to <18 kg BW: LET 120 mg orally without CsA, or 60 mg with CsA, in granular form, or 60 mg IV with or without CsA, all QD through week 14 (~ 100 days) post-transplant. | ||
Reporting group title |
Birth - <2 Years
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Reporting group description |
10 to ≤15 kg BW: LET 120 mg orally without CsA, or 60 mg with CsA, in granular form, or 60 mg IV with or without CsA; 7.5 to <10 kg BW: LET 80 mg orally without CsA, or 40 mg with CsA, either in granular form, or 40 mg IV with or without CsA; 5.0 to <7.5 kg BW: LET 40 mg orally without CsA, or 20 mg with CsA, in granular form, or 20 mg IV with or without CsA; 2.5 to <5.0 kg BW: LET 20 mg orally without CsA, or 10 mg with CsA, in granular form, or 10 mg IV with or without CsA, all QD through week 14 (~ 100 days) post-transplant. | ||
Reporting group title |
12 - <18 Years
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||
Reporting group description |
Letermovir (LET) 480 mg without cyclosporin (CsA), or 240 mg with CsA, administered either orally as tablets or in granular form, or by intravenous (IV) infusion, once daily (QD) through week 14 (~ 100 days) post-transplant. | ||
Reporting group title |
2 - <12 Years
|
||
Reporting group description |
Participants ≥30 kg body weight (BW): LET 480 mg orally without CsA, or 240 mg with CsA, in granular form, or 240 mg IV with or without CsA; 18 to <30 kg BW: LET 240 mg orally without CsA, or 120 mg with CsA, either in granular form, or 120 mg IV with or without CsA; 10 to <18 kg BW: LET 120 mg orally without CsA, or 60 mg with CsA, in granular form, or 60 mg IV with or without CsA, all QD through week 14 (~ 100 days) post-transplant. | ||
Reporting group title |
Birth - <2 Years
|
||
Reporting group description |
10 to ≤15 kg BW: LET 120 mg orally without CsA, or 60 mg with CsA, in granular form, or 60 mg IV with or without CsA; 7.5 to <10 kg BW: LET 80 mg orally without CsA, or 40 mg with CsA, either in granular form, or 40 mg IV with or without CsA; 5.0 to <7.5 kg BW: LET 40 mg orally without CsA, or 20 mg with CsA, in granular form, or 20 mg IV with or without CsA; 2.5 to <5.0 kg BW: LET 20 mg orally without CsA, or 10 mg with CsA, in granular form, or 10 mg IV with or without CsA, all QD through week 14 (~ 100 days) post-transplant. | ||
Subject analysis set title |
12 - <18 Years
|
||
Subject analysis set type |
Per protocol | ||
Subject analysis set description |
LET 480 mg without CsA as tablets or in granular form, was administered orally, QD through week 14 (~ 100 days) post-transplant.
|
||
Subject analysis set title |
2 - <12 Years
|
||
Subject analysis set type |
Per protocol | ||
Subject analysis set description |
LET administered orally in granular form without CsA within 28 days post-transplant, QD through week 14 (approximately 100 days). Dosing varied based on weight.
|
||
Subject analysis set title |
Birth - <2 Years
|
||
Subject analysis set type |
Per protocol | ||
Subject analysis set description |
LET administered orally in granular form without CsA within 28 days post-transplant, QD through week 14 (approximately 100 days). Dosing varied based on weight.
|
||
Subject analysis set title |
2 - <12 Years, 18 to <30 kg BW
|
||
Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Participants 18 to <30 kg BW)received LET 240 mg without CsA orally in granular form QD through week 14 (~ 100 days) post-transplant.
|
||
Subject analysis set title |
Birth - <2 Years, 5 to <7.5 kg BW
|
||
Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Participants 5 to <7.5 kg BW received LET 60 mg orally without CsA, in granular form, QD through week 14 (~ 100 days) post-transplant.
|
||
Subject analysis set title |
2 - <12 Years, 10 to <18 kg BW
|
||
Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Participants 10 to <18 kg BW received LET 120 mg without CsA orally in granular form QD through week 14 (~ 100 days) post-transplant.
|
||
Subject analysis set title |
Birth - <2 Years, 7.5 to <10 kg BW
|
||
Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Participants 7.5 to <10 kg BW received LET 40 mg orally without CsA, in granular form, QD through week 14 (~ 100 days) post-transplant.
|
||
Subject analysis set title |
Birth - <2 Years, 5 to <7.5 kg BW
|
||
Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Participants 5 to <7.5 kg BW received LET 60 mg orally without CsA, in granular form, QD through week 14 (~ 100 days) post-transplant.
|
||
Subject analysis set title |
12 - <18 Years
|
||
Subject analysis set type |
Per protocol | ||
Subject analysis set description |
LET 480 mg without CsA was administered by IV, QD through week 14 (~ 100 days) post-transplant.
|
||
Subject analysis set title |
2 - <12 Years, ≥30 kg BW
|
||
Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Participants ≥30 kg BW received LET 240 mg without CsA orally by IV QD through week 14 (~ 100 days) post-transplant.
|
||
Subject analysis set title |
2 - <12 Years, 18 to <30 kg BW
|
||
Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Participants 18 to <30 kg BW received LET 120 mg without CsA, by IV QD through week 14 (~ 100 days) post-transplant.
|
||
Subject analysis set title |
2 - <12 Years, 18 to <30 kg BW
|
||
Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Participants 18 to <30 kg BW received LET 240 mg without CsA by IV QD through week 14 (~ 100 days) post-transplant.
|
||
Subject analysis set title |
2 - <12 Years, 10 to <18 kg BW
|
||
Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Participants 10 to <18 kg BW received LET 60 mg without CsA by IV QD through week 14 (~ 100 days) post-transplant.
|
||
Subject analysis set title |
Birth - <2 Years, 5 to <7.5 kg BW
|
||
Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Participants 5.0 to <7.5 kg BW received LET 40 mg without CsA, by IV QD through week 14 (~ 100 days) post-transplant.
|
||
Subject analysis set title |
Birth - <2 Years, 7.5 to <10 kg BW
|
||
Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Participants 7.5 to <10 kg BW received LET 40 mg without CsA, by IV, QD through week 14 (~ 100 days) post-transplant.
|
||
Subject analysis set title |
2 - <12 Years
|
||
Subject analysis set type |
Per protocol | ||
Subject analysis set description |
LET administered by IV within 28 days post-transplant, QD without CsA through week 14 (approximately 100 days). Dosing varied based on weight.
|
||
Subject analysis set title |
Birth - <2 Years
|
||
Subject analysis set type |
Per protocol | ||
Subject analysis set description |
LET administered by IV without CsA within 28 days post-transplant, QD through week 14 (approximately 100 days). Dosing varied based on weight.
|
|
|||||||||||||||||
End point title |
Area under the concentration-time curve from time 0 to 24 hours post-dose (AUC0-24) of plasma letermovir taken as oral formulation by ages 2 - <18 years [1] | ||||||||||||||||
End point description |
Blood was collected on treatment Day 7 from participants aged 2 - <18 years in order to determine the AUC0-24 of plasma letermovir for participants receiving oral formulation. Individual values were natural log transformed and evaluated separately with a linear mixed effects model containing a fixed effect for treatment and a random effect for participant. The population analyzed was all participants with at least one measurable PK sample who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
|
||||||||||||||||
Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical comparisons between treatment groups were neither planned or performed for this primary endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [2] - Data analysis resulted in a different measure type and method of dispersion. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
AUC0-24 of plasma letermovir taken as oral formulation by ages 2 to <12 years [3] | ||||||||||||||||
End point description |
Blood was collected on treatment Day 7 from participants aged 2 to <12 years in order to determine the AUC0-24 of plasma letermovir for participants receiving oral formulation. Individual values were natural log transformed and evaluated separately with a linear mixed effects model containing a fixed effect for treatment and a random effect for participant. The population analyzed was all participants with at least one measurable PK sample who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
|
||||||||||||||||
Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical comparisons between treatment groups were neither planned or performed for this primary endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [4] - data analysis resulted in a different measure type and method of dispersion. [5] - Data analysis resulted in a different measure type and method of dispersion. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
AUC0-24 of plasma letermovir taken as oral formulation by ages <2 years [6] | ||||||||||||||||
End point description |
Blood was collected on treatment Day 7 from participants aged <2 years in order to determine the AUC0-24 of plasma letermovir for participants receiving oral formulation. Individual values were natural log transformed and evaluated separately with a linear mixed effects model containing a fixed effect for treatment and a random effect for participant. The measure of dispersion is not determined when N <2. The population analyzed was all participants with at least one measurable PK sample who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
|
||||||||||||||||
Notes [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical comparisons between treatment groups were neither planned or performed for this primary endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [7] - Data analysis resulted in a different measure type and method of dispersion. [8] - Data analysis resulted in a different measure type and method of dispersion. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Maximal concentration (Cmax) of plasma letermovir taken as oral formulation by ages 2 - <18 years [9] | ||||||||||||||||
End point description |
Blood was collected on treatment Day 7 from participants aged 2 - <18 years in order to determine the Cmax of plasma letermovir for participants receiving oral formulation. Individual values were natural log transformed and evaluated separately with a linear mixed effects model containing a fixed effect for treatment and a random effect for participant. The measure type is geometric least squares mean. Participants aged < 2 years were not presented as their data analysis resulted in a different measure type and method of dispersion. The population analyzed was all participants with at least one measurable PK sample who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
|
||||||||||||||||
Notes [9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical comparisons between treatment groups were neither planned or performed for this primary endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [10] - Data analysis resulted in a different measure type and method of dispersion. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Cmax of plasma letermovir taken as oral formulation by ages 2 to <12 years [11] | ||||||||||||||||
End point description |
Blood was collected on treatment Day 7 from participants aged 2 to <12 years in order to determine Cmax of plasma letermovir for participants receiving oral formulation. Individual values were natural log transformed and evaluated separately with a linear mixed effects model containing a fixed effect for treatment and a random effect for participant. Participants aged <2 and >12 years were not presented as their data analysis resulted in a different measure type and method of dispersion. The population analyzed was all participants with at least one measurable PK sample who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
|
||||||||||||||||
Notes [11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical comparisons between treatment groups were neither planned or performed for this primary endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [12] - Data analysis resulted in a different measure type and method of dispersion. [13] - Data analysis resulted in a different measure type and method of dispersion. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Cmax of plasma letermovir taken as oral formulation by ages < 2 years [14] | ||||||||||||||||
End point description |
Blood was collected on treatment Day 7 from participants aged <2 years in order to determine the Cmax of plasma letermovir for participants receiving oral formulation. Individual values were natural log transformed and evaluated separately with a linear mixed effects model containing a fixed effect for treatment and a random effect for participant. Participants aged 2 - <18 years were not presented as their data analysis resulted in a different measure type and method of dispersion. The measure of dispersion is not determined when N <2. The population analyzed was all participants with at least one measurable PK sample who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
|
||||||||||||||||
Notes [14] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical comparisons between treatment groups were neither planned or performed for this primary endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [15] - Data analysis resulted in a different measure type and method of dispersion. [16] - Data analysis resulted in a different measure type and method of dispersion. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Minimum concentration of plasma letermovir observed before next dose (Ctrough) taken as oral formulation by ages 2 - <18 years [17] | ||||||||||||||||
End point description |
Blood was collected on treatment Day 7 from participants aged 2 - <18 years in order to determine the Ctrough of plasma letermovir for participants receiving oral formulation. Individual values were natural log transformed and evaluated separately with a linear mixed effects model containing a fixed effect for treatment and a random effect for participant. Participants aged < 2 years were not presented as their data analysis resulted in a different measure type and method of dispersion. The measure type is geometric least squares mean. The population analyzed was all participants with at least one measurable PK sample who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Day 7: 24 hours post-dose
|
||||||||||||||||
Notes [17] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical comparisons between treatment groups were neither planned or performed for this primary endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [18] - Data analysis resulted in a different measure type and method of dispersion. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Ctrough of plasma letermovir taken as oral formulation by ages 2 to <12 years [19] | ||||||||||||||||
End point description |
Blood was collected on treatment Day 7 from participants aged 2 to <12 years in order to determine Ctrough of plasma letermovir for participants receiving oral formulation. Individual values were natural log transformed and evaluated separately with a linear mixed effects model containing a fixed effect for treatment and a random effect for participant. Participants aged <2 and >12 years were not presented as their data analysis resulted in a different measure type and method of dispersion. The population analyzed was all participants with at least one measurable PK sample who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
|
||||||||||||||||
Notes [19] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical comparisons between treatment groups were neither planned or performed for this primary endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [20] - Data analysis resulted in a different measure type and method of dispersion. [21] - Data analysis resulted in a different measure type and method of dispersion. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Ctrough of plasma letermovir taken as oral formulation by ages < 2 years [22] | ||||||||||||||||
End point description |
Blood was collected on treatment Day 7 from participants aged <2 years in order to determine the Ctrough of plasma letermovir for participants receiving oral formulation. Individual values were natural log transformed and evaluated separately with a linear mixed effects model containing a fixed effect for treatment and a random effect for participant. Participants aged 2 - <18 years were not presented as their data analysis resulted in a different measure type and method of dispersion. The measure of dispersion is not determined when N <2. The population analyzed was all participants with at least one measurable PK sample who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Day 7: 24 hours post-dose
|
||||||||||||||||
Notes [22] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical comparisons between treatment groups were neither planned or performed for this primary endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [23] - Data analysis resulted in a different measure type and method of dispersion. [24] - Data analysis resulted in a different measure type and method of dispersion. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
AUC0-24 of plasma letermovir taken as intravenous (IV) formulation by ages 12 - <18 years [25] | ||||||||||||||||
End point description |
Blood was collected on treatment Day 7 from participants aged 12 - <18 years in order to determine the AUC0-24 of plasma letermovir for participants receiving IV formulation. Individual values were natural log transformed and evaluated separately with a linear mixed effects model containing a fixed effect for treatment and a random effect for participant. The population analyzed was all participants with at least one measurable PK sample who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
|
||||||||||||||||
Notes [25] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical comparisons between treatment groups were neither planned or performed for this primary endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [26] - Data analysis resulted in a different measure type and method of dispersion [27] - Data analysis resulted in a different measure type and method of dispersion |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
AUC0-24 of plasma letermovir taken as IV formulation by ages 2 to <12 years [28] | ||||||||||||||||||||
End point description |
Blood was collected on treatment Day 7 from participants aged 2 to <12 years in order to determine the AUC0-24 of plasma letermovir for participants receiving IV formulation. Individual values were natural log transformed and evaluated separately with a linear mixed effects model containing a fixed effect for treatment and a random effect for participant. The population analyzed was all participants with at least one measurable PK sample who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.
|
||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||
End point timeframe |
Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
|
||||||||||||||||||||
Notes [28] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical comparisons between treatment groups were neither planned or performed for this primary endpoint. |
|||||||||||||||||||||
|
|||||||||||||||||||||
Notes [29] - Data analysis resulted in a different measure type and method of dispersion [30] - Data analysis resulted in a different measure type and method of dispersion |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
AUC0-24 of plasma letermovir taken as IV formulation by ages 2 to <12 years [31] | ||||||||||||||||
End point description |
Blood was collected on treatment Day 7 from participants aged 2 to <12 years in order to determine the AUC0-24 of plasma letermovir for participants receiving IV formulation. Individual values were natural log transformed and evaluated separately with a linear mixed effects model containing a fixed effect for treatment and a random effect for participant. The measure of dispersion is not determined when N <2. The population analyzed was all participants with at least one measurable PK sample who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
|
||||||||||||||||
Notes [31] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical comparisons between treatment groups were neither planned or performed for this primary endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [32] - Data analysis resulted in a different measure type and method of dispersion [33] - Data analysis resulted in a different measure type and method of dispersion |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
AUC0-24 of plasma letermovir taken as IV formulation by ages <2 years [34] | ||||||||||||||||
End point description |
Blood was collected on treatment Day 7 from participants aged <2 years in order to determine the AUC0-24 of plasma letermovir for participants receiving IV formulation. Individual values were natural log transformed and evaluated separately with a linear mixed effects model containing a fixed effect for treatment and a random effect for participant. The measure of dispersion is not determined when N <2. The population analyzed was all participants with at least one measurable PK sample who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
|
||||||||||||||||
Notes [34] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical comparisons between treatment groups were neither planned or performed for this primary endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [35] - Data analysis resulted in a different measure type and method of dispersion [36] - Data analysis resulted in a different measure type and method of dispersion |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Concentration at the end of infusion (Ceoi) of plasma letermovir taken as IV formulation by ages 12 - <18 years [37] | ||||||||||||||||
End point description |
Blood was collected on treatment Day 7 from participants aged 12 - <18 years in order to determine the Ceoi of plasma letermovir for participants receiving IV formulation. As samples were collected outside the collection window Ceoi for these samples were predicted by using a log linear model .The population analyzed was all participants with at least one measurable PK sample who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
|
||||||||||||||||
Notes [37] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical comparisons between treatment groups were neither planned or performed for this primary endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [38] - Data analysis resulted in a different measure type and method of dispersion [39] - Data analysis resulted in a different measure type and method of dispersion |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Ceoi of plasma letermovir taken as IV formulation by ages 2 to <12 years [40] | ||||||||||||||||||||
End point description |
Blood was collected on treatment Day 7 from participants aged 2 to <12 years in order to determine the Ceoi of plasma letermovir for participants receiving IV formulation. As samples were collected outside the collection window Ceoi for these samples were predicted by using a log linear model. The population analyzed was all participants with at least one measurable PK sample who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.
|
||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||
End point timeframe |
Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
|
||||||||||||||||||||
Notes [40] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical comparisons between treatment groups were neither planned or performed for this primary endpoint. |
|||||||||||||||||||||
|
|||||||||||||||||||||
Notes [41] - Data analysis resulted in a different measure type and method of dispersion [42] - Data analysis resulted in a different measure type and method of dispersion |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Ceoi of plasma letermovir taken as IV formulation by ages s 2 to <12 years [43] | ||||||||||||||||
End point description |
Blood was collected on treatment Day 7 from participants aged 2 to <12 years in order to determine the Ceoi of plasma letermovir for participants receiving IV formulation. As samples were collected outside the collection window Ceoi for these samples were predicted by using a log linear model. A measure of dispersion is not determined when N <2. The population analyzed was all participants with at least one measurable PK sample who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
|
||||||||||||||||
Notes [43] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical comparisons between treatment groups were neither planned or performed for this primary endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [44] - Data analysis resulted in a different measure type and method of dispersion [45] - Data analysis resulted in a different measure type and method of dispersion |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Ceoi of plasma letermovir taken as IV formulation by ages <2 years [46] | ||||||||||||||||
End point description |
Blood was collected on treatment Day 7 from participants aged <2 years in order to determine the Ceoi of plasma letermovir for participants receiving IV formulation. As samples were collected outside the collection window Ceoi for these samples were predicted by using a log linear modelA measure of dispersion is not determined when N <2. The population analyzed was all participants with at least one measurable PK sample who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
|
||||||||||||||||
Notes [46] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical comparisons between treatment groups were neither planned or performed for this primary endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [47] - Data analysis resulted in a different measure type and method of dispersion [48] - Data analysis resulted in a different measure type and method of dispersion |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Ctrough of plasma letermovir taken as IV formulation by ages 12 - <18 years [49] | ||||||||||||||||
End point description |
Blood was collected on treatment Day 7 from participants aged 12 - <18 years in order to determine the Ctrough of plasma letermovir for participants receiving IV formulation. Individual values were natural log transformed and evaluated separately with a linear mixed effects model containing a fixed effect for treatment and a random effect for participant. The population analyzed was all participants with at least one measurable PK sample who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Day 7: 24 hours post-dose
|
||||||||||||||||
Notes [49] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical comparisons between treatment groups were neither planned or performed for this primary endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [50] - Data analysis resulted in a different measure type and method of dispersion [51] - Data analysis resulted in a different measure type and method of dispersion |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Ctrough of plasma letermovir taken as IV formulation by ages 2 to <12 years [52] | ||||||||||||||||||||
End point description |
Blood was collected on treatment Day 7 from participants aged 2 to <12 years in order to determine the Ctrough of plasma letermovir for participants receiving IV formulation. Individual values were natural log transformed and evaluated separately with a linear mixed effects model containing a fixed effect for treatment and a random effect for participant. The population analyzed was all participants with at least one measurable PK sample who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.
|
||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||
End point timeframe |
Day 7: 24 hours post-dose
|
||||||||||||||||||||
Notes [52] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical comparisons between treatment groups were neither planned or performed for this primary endpoint. |
|||||||||||||||||||||
|
|||||||||||||||||||||
Notes [53] - Data analysis resulted in a different measure type and method of dispersion [54] - Data analysis resulted in a different measure type and method of dispersion |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Ctrough of plasma letermovir taken as IV formulation by ages 2 to <12 years [55] | ||||||||||||||||
End point description |
Blood was collected on treatment Day 7 from participants aged <2 years in order to determine the Ctrough of plasma letermovir for participants receiving IV formulation. Individual values were natural log transformed and evaluated separately with a linear mixed effects model containing a fixed effect for treatment and a random effect for participant. The measure of dispersion is not determined when N <2. The population analyzed was all participants with at least one measurable PK sample who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
|
||||||||||||||||
Notes [55] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical comparisons between treatment groups were neither planned or performed for this primary endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [56] - Data analysis resulted in a different measure type and method of dispersion [57] - Data analysis resulted in a different measure type and method of dispersion |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Ctrough of plasma letermovir taken as IV formulation by ages <2 years [58] | ||||||||||||||||
End point description |
Blood was collected on treatment Day 7 from participants aged <2 years in order to determine the Ctrough of plasma letermovir for participants receiving IV formulation. Individual values were natural log transformed and evaluated separately with a linear mixed effects model containing a fixed effect for treatment and a random effect for participant. The measure type is Geometric Mean, and a measure of dispersion is not determined when N <2. The population analyzed was all participants with at least one measurable PK sample who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Day 7: Pre-dose, 1, 2.5, 8, and 24 hours post-dose
|
||||||||||||||||
Notes [58] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical comparisons between treatment groups were neither planned or performed for this primary endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [59] - Data analysis resulted in a different measure type and method of dispersion [60] - Data analysis resulted in a different measure type and method of dispersion |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Ctrough of plasma letermovir taken during sparse PK for oral formulation [61] | ||||||||||||||||
End point description |
Blood was collected on treatment Day 7 in order to determine the Ctrough of plasma letermovir during sparse PK for participants receiving oral formulation. Individual values were natural log transformed and evaluated separately with a linear mixed effects model containing a fixed effect for treatment and a random effect for participant.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Day 7: 24 hours post-dose
|
||||||||||||||||
Notes [61] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical comparisons between treatment groups were neither planned or performed for this primary endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [62] - As sparse PK data were instead used in population PK model development, they were not summarized [63] - As sparse PK data were instead used in population PK model development, they were not summarized [64] - As sparse PK data were instead used in population PK model development, they were not summarized |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Ctrough of plasma letermovir taken during sparse PK as IV formulation [65] | ||||||||||||||||
End point description |
Blood was collected on treatment Day 7 in order to determine the Ctrough of plasma letermovir for participants receiving IV formulation during sparse PK. Individual values were natural log transformed and evaluated separately with a linear mixed effects model containing a fixed effect for treatment and a random effect for participant.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Day 7: 24 hours post-dose
|
||||||||||||||||
Notes [65] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical comparisons between treatment groups were neither planned or performed for this primary endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [66] - As sparse PK data were instead used in population PK model development, they were not summarized [67] - As sparse PK data were instead used in population PK model development, they were not summarized [68] - As sparse PK data were instead used in population PK model development, they were not summarized |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Percentage of participants who discontinued study medication due to an AE. | ||||||||||||||||
End point description |
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The 95% CI is based on the exact binomial method proposed by Clopper and Pearson. The population analyzed was all participants who received ≥1 dose of study intervention.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Up to Week 14 post-transplant (up to 18 weeks)
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Percentage of participants with one or more adverse event (AE) | ||||||||||||||||
End point description |
.An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The 95% confidence interval (CI) is based on the exact binomial method proposed by Clopper and Pearson. The population analyzed was all participants who received ≥1 dose of study intervention.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Up to Week 48 post-transplant (up to 52 weeks)
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Percentage of participants with clinically significant CMV infection through Week 14 post-transplant | ||||||||||||||||
End point description |
Clinically significant cytomegalovirus (CMV) infection is defined as CMV end organ disease (proven or probable) or initiation of pre-emptive therapy (PET) based on documented CMV viremia and the clinical condition of the participant. The 95% confidence interval (CI) was based on the exact binomial method proposed by Clopper and Pearson. Missing values: were handled by the Non-Completer=Failure (NC=F) approach. where failure was defined as all participants who developed clinically significant CMV infection or prematurely discontinued from the study or had a missing outcome through week 14 post-transplant visit window. The population analyzed was participants who received ≥1 dose of study intervention, had no detectable CMV viral DNA on the day study intervention was initiated, had not prematurely discontinued from the study and had an outcome through week 14 post-transplant.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Up to Week 14 post-transplant (up to 18 weeks)
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||
End point title |
Number of participants receiving oral granules with palatability response, based on taste of medication on the first day of administration of oral formulation | ||||||||||||||||||||||||||||||||
End point description |
Palatability was measured by response to a questionnaire on the taste of medication , with responses from very good, good, neither good nor bad, bad or very bad. The population analyzed was participants who received ≥1 dose of study intervention, and completed palatability questionnaire.
|
||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||
End point timeframe |
Day 1 of administration of oral formulation up to Week 14 post-transplant (up to 18 weeks)
|
||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Percentage of participants with clinically significant CMV infection through Week 24 post-transplant | ||||||||||||||||
End point description |
Clinically significant CMV infection is defined as CMV end organ disease (proven or probable) or initiation of PET based on documented CMV viremia and the clinical condition of the participant. The 95% confidence interval (CI) was based on the exact binomial method proposed by Clopper and Pearson. Missing values: were handled by the Non-Completer=Failure (NC=F) approach. where failure was defined as all participants who developed clinically significant CMV infection or prematurely discontinued from the study or had a missing outcome through week 24 post-transplant visit window. The population analyzed was participants who received ≥1 dose of study intervention, had no detectable CMV viral DNA on the day study intervention was initiated, had not prematurely discontinued from the study and had an outcome through week 14 post-transplant.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Up to Week 24 post-transplant (up to 28 weeks)
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||
End point title |
Number of participants receiving oral granules with palatability response, based on taste of medication on the eighth day of administration of oral formulation | ||||||||||||||||||||||||||||||||
End point description |
Palatability was measured by response to a questionnaire on the taste of medication , with responses from very good, good, neither good nor bad, bad or very bad. The population analyzed was participants who received ≥1 dose of study intervention, and completed palatability questionnaire.
|
||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||
End point timeframe |
Day 8 of administration of oral formulation up to Week 14 post-transplant (up to 18 weeks)
|
||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
All-cause mortality (ACM): from allocation/randomization (i.e. prior to treatment) up to Week 48 post-transplant (up to 52 weeks). AEs: From first treatment up to Week 48 post-transplant (up to 52 weeks)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
ACMs: the population analyzed was all allocated/randomized participants.
AEs: the population analyzed was all allocated/randomized participants who received ≥1 dose of study intervention.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
26.0
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Reporting groups
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Reporting group title |
12 - <18 Years
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Reporting group description |
LET 480 mg without CsA, or 240 mg with CsA, administered either orally as tablets or in granular form, or by iIV infusion, QD through week 14 (~ 100 days) post-transplant. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
<2 Years
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Reporting group description |
10 to ≤15 kg BW: LET 120 mg orally without CsA, or 60 mg with CsA, in granular form, or 60 mg IV with or without CsA; 7.5 to <10 kg BW: LET 80 mg orally without CsA, or 40 mg with CsA, either in granular form, or 40 mg IV with or without CsA; 5.0 to <7.5 kg BW: LET 40 mg orally without CsA, or 20 mg with CsA, in granular form, or 20 mg IV with or without CsA; 2.5 to <5.0 kg BW: LET 20 mg orally without CsA, or 10 mg with CsA, in granular form, or 10 mg IV with or without CsA, all QD through week 14 (~ 100 days) post-transplant. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
2 - <12 Years
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Reporting group description |
Participants ≥30 kg BW: LET 480 mg orally without CsA, or 240 mg with CsA, in granular form, or 240 mg IV with or without CsA; 18 to <30 kg BW: LET 240 mg orally without CsA, or 120 mg with CsA, either in granular form, or 120 mg IV with or without CsA; 10 to <18 kg BW: LET 120 mg orally without CsA, or 60 mg with CsA, in granular form, or 60 mg IV with or without CsA, all QD through week 14 (~ 100 days) post-transplant. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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14 Mar 2019 |
Amendment 01: Testicular toxicity testing was removed, and creatinine clearance monitoring every 2 weeks was added to the protocol. |
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03 Apr 2019 |
Amendment 02: The description of the coating of the oral granule formulation to be used in this study provided in Section 2.2.4 was incorrect in the original protocol. This amendment provides the correct description of the coating of the oral granule formulation being used (Opadry coating without Surelease) and provides the rationale for selection of this oral granule formulation. Additional minor changes have been made to incorporate changes communicated in prior protocol clarification letters. |
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27 Sep 2019 |
Amendment 03: To add the requirement that the IV formulation of LET supplied by the Sponsor to sites as study medication must be administered through a sterile 0.2-micron or 0.22-micron polyethersulfone (PES) in-line filter and using diethylhexyl phthalate (DEHP)-free IV bags and infusion set materials. This requirement is being added to prevent the possible administration of product-related particulate matter. The presence of visible product-related particulate matter is an expected characteristic of new clinical supplies of the IV formulation of LET. This requirement is being implemented to allow for the release of new clinical supplies of IV LET, and, as a precaution, it must be applied regardless of whether the clinical
site considers its current clinical supply to be impacted. |
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01 Oct 2021 |
Amendment 07: To provide the initial dose of oral and IV LET for Age Group 3, which has been determined by interim pharmacokinetics (PK) analyses using data from participants in Age Group 1 and Age Group 2 of this study. To add a requirement for PK sampling of hydroxypropyl-beta-cyclodextrin (HPCD), an excipient in the IV LET formulation, for Age Group 3 participants receiving the IV formulation for at least 4 consecutive days. In addition, the 10-mg oral capsule of LET is now available for use in Spain. |
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21 Oct 2022 |
Amendment 08:The primary reason was Sponsor underwent entity name change and update to the address. |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |