Clinical Trial Results:
Four weeks treatment for chronic hepatitis C in patients under 50 years of age with no significant liver fibrosis
Summary
|
|
EudraCT number |
2017-005179-21 |
Trial protocol |
DK |
Global end of trial date |
11 Aug 2021
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
17 Sep 2022
|
First version publication date |
17 Sep 2022
|
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 |
4RIBC-2018
|
||
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
|
|||
Sponsor organisation name |
Clinical Institute, University of Southern Denmark
|
||
Sponsor organisation address |
J.B. Winsløwsvej 4, Indgang 18, Penthous, Odense C, Denmark, 5000
|
||
Public contact |
Deparment of infectious Diseases, Odense University Hospital, 0045 28834681, lone.wulff.madsen@rsyd.dk
|
||
Scientific contact |
Deparment of infectious Diseases, Odense University Hospital, lone.wulff.madsen@rsyd.dk
|
||
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
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? |
No
|
||
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
22 Feb 2022
|
||
Is this the analysis of the primary completion data? |
Yes
|
||
Primary completion date |
11 Aug 2021
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
11 Aug 2021
|
||
Was the trial ended prematurely? |
Yes
|
||
General information about the trial
|
|||
Main objective of the trial |
To compare the percentage of subjects achieving a 12-week sustained virological response, SVR 12 (HCV RNA below lower limit of quantification at week 12 after end of treatment) after 4 weeks of treatment (including forward moving arm from phase 1) compared to 8 weeks of treatment in the intention to treat population including all subjects taking at least one dose of study medication.
|
||
Protection of trial subjects |
because of the study criteria, no one suffered from severe liver disease, and based on previous retreatment studies after
short treatment, the likelihood of cure after retreatment was high.
All patients who experienced treatment failure have been offered retreatment.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
03 May 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 |
Denmark: 61
|
||
Worldwide total number of subjects |
61
|
||
EEA total number of subjects |
61
|
||
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) |
0
|
||
Adults (18-64 years) |
61
|
||
From 65 to 84 years |
0
|
||
85 years and over |
0
|
|
|||||||||||||
Recruitment
|
|||||||||||||
Recruitment details |
The first 33 patients were all included at the outpatient clinic at Odense University hospital. The 28 last patients were included at outreach clinics at drug treatment centers and at the outpatient clinic at Odense University hospital. | ||||||||||||
Pre-assignment
|
|||||||||||||
Screening details |
- | ||||||||||||
Pre-assignment period milestones
|
|||||||||||||
Number of subjects started |
61 | ||||||||||||
Number of subjects completed |
53 | ||||||||||||
Pre-assignment subject non-completion reasons
|
|||||||||||||
Reason: Number of subjects |
Protocol deviation: 2 | ||||||||||||
Reason: Number of subjects |
Consent withdrawn by subject: 6 | ||||||||||||
Period 1
|
|||||||||||||
Period 1 title |
Overall trial (overall period)
|
||||||||||||
Is this the baseline period? |
Yes | ||||||||||||
Allocation method |
Randomised - controlled
|
||||||||||||
Blinding used |
Not blinded | ||||||||||||
Arms
|
|||||||||||||
Are arms mutually exclusive |
Yes
|
||||||||||||
Arm title
|
Intervention | ||||||||||||
Arm description |
Glecaprevir/Pibrentasvir was given with ribavirin for 4 weeks | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
Maviret
|
||||||||||||
Investigational medicinal product code |
|||||||||||||
Other name |
Glecaprevir/Pibrentasvir
|
||||||||||||
Pharmaceutical forms |
Coated tablet
|
||||||||||||
Routes of administration |
Oral use
|
||||||||||||
Dosage and administration details |
100mg glecaprevir and 40 mg pibrentasvir, 3 tablets once daily at the same time with food.
|
||||||||||||
Investigational medicinal product name |
Ribavirin
|
||||||||||||
Investigational medicinal product code |
|||||||||||||
Other name |
Moderiba/copegus/
|
||||||||||||
Pharmaceutical forms |
Tablet
|
||||||||||||
Routes of administration |
Oral use
|
||||||||||||
Dosage and administration details |
15mg/kg with a maximum of 1400mg. Dosed twice daily for the first 15 patients and for the rest in this intervention group once daily
|
||||||||||||
Arm title
|
Intervention 2 | ||||||||||||
Arm description |
Glecaprevir/pibrentasvir given for 4 weeks | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
Maviret
|
||||||||||||
Investigational medicinal product code |
|||||||||||||
Other name |
Glecaprevir/pibrentasvir
|
||||||||||||
Pharmaceutical forms |
Coated tablet
|
||||||||||||
Routes of administration |
Oral use
|
||||||||||||
Dosage and administration details |
100mg glecaprevir/40 mg pibrentasvir, 3 tablets once daily with food
|
||||||||||||
Arm title
|
GLE/PIB for 8 weeks | ||||||||||||
Arm description |
Standard of care with GLE/PIB for 8 weeks for treatment of chronic hepatitis C | ||||||||||||
Arm type |
standard of care | ||||||||||||
Investigational medicinal product name |
Maviret
|
||||||||||||
Investigational medicinal product code |
|||||||||||||
Other name |
Glecaprevir/Pibrentasvir
|
||||||||||||
Pharmaceutical forms |
Coated tablet
|
||||||||||||
Routes of administration |
Oral use
|
||||||||||||
Dosage and administration details |
100mg glecaprevir and 40 mg pibrentasvir, 3 tablets once daily at the same time with food.
|
||||||||||||
|
|||||||||||||
Notes [1] - 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: 61 patients were enrolled. A total of 53 patients started treatment divided at the three treatment arms. |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Intervention
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Glecaprevir/Pibrentasvir was given with ribavirin for 4 weeks | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Intervention 2
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Glecaprevir/pibrentasvir given for 4 weeks | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
GLE/PIB for 8 weeks
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Standard of care with GLE/PIB for 8 weeks for treatment of chronic hepatitis C | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
End points reporting groups
|
|||
Reporting group title |
Intervention
|
||
Reporting group description |
Glecaprevir/Pibrentasvir was given with ribavirin for 4 weeks | ||
Reporting group title |
Intervention 2
|
||
Reporting group description |
Glecaprevir/pibrentasvir given for 4 weeks | ||
Reporting group title |
GLE/PIB for 8 weeks
|
||
Reporting group description |
Standard of care with GLE/PIB for 8 weeks for treatment of chronic hepatitis C |
|
|||||||||||||
End point title |
SVR12 | ||||||||||||
End point description |
How many were cured of hepatitis C
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
12 weeks after end of treatment
|
||||||||||||
|
|||||||||||||
Notes [1] - one patient lost to follow up [2] - one patient lost to follow up |
|||||||||||||
Statistical analysis title |
percent | ||||||||||||
Comparison groups |
Intervention v Intervention 2 v GLE/PIB for 8 weeks
|
||||||||||||
Number of subjects included in analysis |
51
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other [3] | ||||||||||||
P-value |
= 0.749 [4] | ||||||||||||
Method |
Fisher exact | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Confidence interval |
|||||||||||||
Notes [3] - The study closed prematurely due to the low number of included patients due to the COVID-19 pandemic. [4] - 4 weeks treatment with maviret + ribavirin compared to maviret for 4 weeks |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
12 weeks after end of treatment
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
20
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
4 weeks maviret+ ribavirin
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
maviret 4 weeks
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
maviret 8 weeks
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? No | |||
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 | |||
Online references |
|||
http://www.ncbi.nlm.nih.gov/pubmed/34154034 http://www.ncbi.nlm.nih.gov/pubmed/35337021 |