Clinical Trial Results:
Open-Label, Single-Arm Trial to Evaluate the Pharmacokinetics, Safety and Efficacy of Daclatasvir (DCV) in Combination with Sofosbuvir (SOF) in Children from 3 to less than 18 Years of Age with GT-1 to -6 Chronic Hepatitis C (CHC) Infection
|
Summary
|
|
EudraCT number |
2017-003338-94 |
Trial protocol |
DE ES PL Outside EU/EEA |
Global end of trial date |
17 Sep 2020
|
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
28 Mar 2021
|
First version publication date |
28 Mar 2021
|
Other versions |
|
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
|
Trial identification
|
|||
Sponsor protocol code |
AI444-423
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
|
Sponsors
|
|||
Sponsor organisation name |
Bristol-Myers Squibb
|
||
Sponsor organisation address |
Chaussée de la Hulpe 185, Brussels, Belgium, 1170
|
||
Public contact |
EU Study Start-Up Unit, Bristol-Myers Squibb International Corporation, Clinical.Trials@bms.com
|
||
Scientific contact |
Bristol-Myers Squibb Study Director, Bristol-Myers Squibb, Clinical.Trials@bms.com
|
||
|
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
|
||
EMA paediatric investigation plan number(s) |
EMEA-001191-PIP01-11 | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
|
||
|
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
12 Nov 2020
|
||
Is this the analysis of the primary completion data? |
No
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
17 Sep 2020
|
||
Was the trial ended prematurely? |
Yes
|
||
|
General information about the trial
|
|||
Main objective of the trial |
To Evaluate the Pharmacokinetics, Safety and Efficacy of Daclatasvir (DCV) in Combination with Sofosbuvir (SOF) in Children from 3 to less than 18 Years of Age with GT-1 to -6 Chronic Hepatitis C (CHC) Infection
|
||
Protection of trial subjects |
The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization Good Clinical Practice Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
25 Jun 2018
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
No
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Spain: 2
|
||
Country: Number of subjects enrolled |
Australia: 3
|
||
Worldwide total number of subjects |
5
|
||
EEA total number of subjects |
2
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
5
|
||
Adults (18-64 years) |
0
|
||
From 65 to 84 years |
0
|
||
85 years and over |
0
|
||
|
|||||||||||
|
Recruitment
|
|||||||||||
Recruitment details |
- | ||||||||||
|
Pre-assignment
|
|||||||||||
Screening details |
5 participants were enrolled and treated | ||||||||||
|
Period 1
|
|||||||||||
Period 1 title |
Overall Study (overall period)
|
||||||||||
Is this the baseline period? |
Yes | ||||||||||
Allocation method |
Non-randomised - controlled
|
||||||||||
Blinding used |
Not blinded | ||||||||||
|
Arms
|
|||||||||||
|
Arm title
|
Daclatasvir (DCV) + Sofosbuvir (SOF) | ||||||||||
Arm description |
DCV 60 mg QD + SOF 400 mg QD for 12 weeks | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
Sofosbuvir
|
||||||||||
Investigational medicinal product code |
|||||||||||
Other name |
|||||||||||
Pharmaceutical forms |
Film-coated tablet
|
||||||||||
Routes of administration |
Oral use
|
||||||||||
Dosage and administration details |
400 mg QD
|
||||||||||
Investigational medicinal product name |
Daclatasvir
|
||||||||||
Investigational medicinal product code |
|||||||||||
Other name |
|||||||||||
Pharmaceutical forms |
Film-coated tablet
|
||||||||||
Routes of administration |
Oral use
|
||||||||||
Dosage and administration details |
60 mg QD
|
||||||||||
|
|||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Daclatasvir (DCV) + Sofosbuvir (SOF)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
DCV 60 mg QD + SOF 400 mg QD for 12 weeks | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
Daclatasvir (DCV) + Sofosbuvir (SOF)
|
||
Reporting group description |
DCV 60 mg QD + SOF 400 mg QD for 12 weeks | ||
|
|||||||||
End point title |
Minimum (Trough) Observed Plasma Concentration (Cmin) for Daclatasvir [1] | ||||||||
End point description |
|||||||||
End point type |
Primary
|
||||||||
End point timeframe |
Day 10 after first 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: No statistical analysis was performed for this endpoint. |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Maximum Observed Plasma Concentration (Cmax) for Daclatasvir [2] | ||||||||
End point description |
|||||||||
End point type |
Primary
|
||||||||
End point timeframe |
Day 10 after first dose
|
||||||||
| Notes [2] - 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: No statistical analysis was performed for this endpoint. |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Time of Maximum Observed Plasma Concentration (Tmax) for Daclatasvir [3] | ||||||||
End point description |
|||||||||
End point type |
Primary
|
||||||||
End point timeframe |
Day 10 after first 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: No statistical analysis was performed for this endpoint. |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Area Under the Concentration-Time Curve (AUC(TAU)) for Daclatasvir [4] | ||||||||
End point description |
|||||||||
End point type |
Primary
|
||||||||
End point timeframe |
Day 10 after first dose
|
||||||||
| Notes [4] - 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: No statistical analysis was performed for this endpoint. |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Apparent Total Body Clearance (CLT/F) for Daclatasvir [5] | ||||||||
End point description |
|||||||||
End point type |
Primary
|
||||||||
End point timeframe |
Day 10 after first dose
|
||||||||
| Notes [5] - 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: No statistical analysis was performed for this endpoint. |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||||||
End point title |
Number of Participants Experiencing Adverse Events | ||||||||||||
End point description |
This outcome describes the number of participants experiencing different types of any grade adverse events.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From first dose to last dose (12 weeks)
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||
End point title |
Number of Participants Experiencing Laboratory Abnormalities - On-treatment analysis | ||||||||
End point description |
Laboratory tests abnormalities were analyzed in the following categories:
-Hematology (hemoglobin, platelets, international normalized ratio (INR), white blood cell count (WBC), lymphocytes (absolute), neutrophils + bands (absolute; ANC)).
-Hepatobiliary enzymes (ALT, AST, alkaline phosphatase, total bilirubin, albumin).
-Pancreatic enzymes (lipase, creatinine).
Tests results were reported by worst toxicity grade (0 to 4) based on the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events (2017).
Only laboratory abnormalities with a worst toxicity grade 3 or higher in any of the above-mentioned tests, experienced during the on-treatment period, are reported here.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
From the day after first dose to last dose (approximately 12 weeks)
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Number of Participants Experiencing Laboratory Abnormalities - Follow-up analysis | ||||||||
End point description |
Laboratory tests abnormalities were analyzed in the following categories:
-Hematology (hemoglobin, platelets, international normalized ratio (INR), white blood cell count (WBC), lymphocytes (absolute), neutrophils + bands (absolute; ANC)).
-Hepatobiliary enzymes (ALT, AST, alkaline phosphatase, total bilirubin, albumin).
-Pancreatic enzymes (lipase, creatinine).
Tests results were reported by worst toxicity grade (0 to 4) based on the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events (2017).
Only laboratory abnormalities with a worst toxicity grade 3 or higher in any of the above-mentioned tests, experienced during the follow-up period, are reported here.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
From the day after last dose to end of follow-up period (up to approximately 96 weeks)
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Percentage of Participants with Hepatitis C Virus (HCV) RNA Levels Below the Lower Limit of Quantitation (LLOQ) at Post-Treatment Follow-Up Week 12 | ||||||||
End point description |
HCV RNA levels were measured by using the Roche COBAS® AmpliPrep/COBAS® TaqMan® HCV Test v2.0. This assay has limit of detection = 15 IU/mL, LLOQ = 15 IU/mL.
The outcome includes both results where Target was Detected (TD) but below LLOQ and results were Target was Not Detected (TND)
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
12 weeks after last dose
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
From first dose to 30 days following last dose
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
23.0
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Daclatasvir (DCV) + Sofosbuvir (SOF)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
DCV 60 mg QD + SOF 400 mg QD for 12 weeks | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
18 Dec 2019 |
- Early termination of the study
- No participants enrolled in Cohorts 2 and 3
- Reduction of the Long-term follow-up period
- Removal of analysis for some secondary and exploratory endpoints
- Removal of interim analysis |
||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
