Clinical Trial Results:
An Open, Multicentre, Phase IV Study, Evaluating the Effect of a Drop In Hemoglobin Level on the Rate of Sustained Virologic Response In Chronic Hepatitis C Patients Treated With Ribavirin (Copegus®) in Combination With Standard Treatment (ANECO)
|
Summary
|
|
EudraCT number |
2011-001256-10 |
Trial protocol |
CZ |
Global end of trial date |
22 Jan 2014
|
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
14 Jul 2016
|
First version publication date |
06 Aug 2015
|
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 |
ML25186
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT01585324 | ||
WHO universal trial number (UTN) |
- | ||
|
Sponsors
|
|||
Sponsor organisation name |
F. Hoffmann-La Roche AG
|
||
Sponsor organisation address |
Grenzacherstrasse 124, Basel, Switzerland, CH-4070
|
||
Public contact |
Roche Trial Information Hotline, F. Hoffmann-La Roche AG, 41 616878333, global.trial_information@roche.com
|
||
Scientific contact |
Roche Trial Information Hotline, F. Hoffmann-La Roche AG, 41 616878333, global.trial_information@roche.com
|
||
|
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 Jan 2014
|
||
Is this the analysis of the primary completion data? |
No
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
22 Jan 2014
|
||
Was the trial ended prematurely? |
No
|
||
|
General information about the trial
|
|||
Main objective of the trial |
The main objective of this clinical study was the determination of a possible coincidence between the drop in hemoglobin concentration and the number of achieved sustained virologic response (SVR) in participants with chronic hepatitis C, infected by genotype 1, treated with ribavirin (Copegus®) in a combination with standard treatment of chronic hepatitis C (peginterferon alpha-2a).
|
||
Protection of trial subjects |
The clinical study was performed in accordance with ICH-GCP and Declaration of Helsinki.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
04 Jan 2012
|
||
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 |
Czech Republic: 30
|
||
Worldwide total number of subjects |
30
|
||
EEA total number of subjects |
30
|
||
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) |
30
|
||
From 65 to 84 years |
0
|
||
85 years and over |
0
|
||
|
|||||||
|
Recruitment
|
|||||||
Recruitment details |
- | ||||||
|
Pre-assignment
|
|||||||
Screening details |
This clinical trial was originally planned in 4 clinical trial centers in the Czech Republic. However, due to a failure in manufacturing of the drug Pegasys, three of the previously approved study centers withdrew from participation. Consequently the sponsor decided to conduct the clinical trial in one of the four originally planned centers. | ||||||
|
Period 1
|
|||||||
Period 1 title |
Overall Study Period (overall period)
|
||||||
Is this the baseline period? |
Yes | ||||||
Allocation method |
Non-randomised - controlled
|
||||||
Blinding used |
Not blinded | ||||||
|
Arms
|
|||||||
|
Arm title
|
Peginterferon Alpha-2a + Ribavirin | ||||||
Arm description |
Participants infected with hepatitis C virus (HCV) genotype 1, who were either treatment naïve or failed to respond to previous combination therapy with interferon and ribavirin, were included in the study. These participants were treated with a combination therapy of peginterferon alpha-2a injection at a dose of 180 micrograms (mcg) subcutaneously once a week and ribavirin tablet, 1000-1200 milligrams (mg) by body weight (1000 mg if weight less than [<] 75 kilogram [kg]; 1200 mg if weight greater than or equal to [≥] 75 kg) orally split into 2 daily divided doses, for a total of 48 weeks . | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
Ribavirin
|
||||||
Investigational medicinal product code |
|||||||
Other name |
Copegus
|
||||||
Pharmaceutical forms |
Coated tablet
|
||||||
Routes of administration |
Oral use
|
||||||
Dosage and administration details |
Ribavirin 1000-1200 mg by body weight (1000 mg if weight <75 kg; 1200 mg if weight ≥75 kg) tablet orally once daily in 2 divided doses, for a total of 48 weeks.
|
||||||
Investigational medicinal product name |
Peginterferon alpha-2a
|
||||||
Investigational medicinal product code |
|||||||
Other name |
Pegasys
|
||||||
Pharmaceutical forms |
Solution for injection in pre-filled syringe
|
||||||
Routes of administration |
Subcutaneous use
|
||||||
Dosage and administration details |
Peginterferon alpha-2a at a dose of 180 mcg subcutaneously once a week, for a total of 48 weeks.
|
||||||
|
|||||||
|
||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
||||||||||||||||||||||||||||||||||
Reporting group title |
Overall Study Period
|
|||||||||||||||||||||||||||||||||
Reporting group description |
All participants who received at least 1 dose of study drug were included. | |||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
Peginterferon Alpha-2a + Ribavirin
|
||
Reporting group description |
Participants infected with hepatitis C virus (HCV) genotype 1, who were either treatment naïve or failed to respond to previous combination therapy with interferon and ribavirin, were included in the study. These participants were treated with a combination therapy of peginterferon alpha-2a injection at a dose of 180 micrograms (mcg) subcutaneously once a week and ribavirin tablet, 1000-1200 milligrams (mg) by body weight (1000 mg if weight less than [<] 75 kilogram [kg]; 1200 mg if weight greater than or equal to [≥] 75 kg) orally split into 2 daily divided doses, for a total of 48 weeks . | ||
Subject analysis set title |
Participants With SVR
|
||
Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Included all participants infected with HCV genotype 1, who were either treatment naïve or failed to respond to previous combination therapy with interferon and ribavirin, but achieved SVR after treatment with a combination therapy of peginterferon alpha-2a at a dose of 180 mcg subcutaneously once a week and ribavirin 1000-1200 mg by body weight (1000 mg if weight <75 kg; 1200 mg if weight ≥75 kg) orally once daily in 2 divided doses, for a total of 48 weeks. SVR response was defined as a disappearance of HCV viral load 24 weeks after the end of the treatment.
|
||
Subject analysis set title |
Participants Without SVR
|
||
Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Included all participants infected with HCV genotype 1, who were either treatment naïve or failed to respond to previous combination therapy with interferon and ribavirin, and did not achieve SVR after treatment with a combination therapy of peginterferon alpha-2a at a dose of 180 mcg subcutaneously once a week and ribavirin 1000-1200 mg by body weight (1000 mg if weight <75 kg; 1200 mg if weight ≥75 kg) orally once daily in 2 divided doses, for a total of 48 weeks. SVR response was defined as a disappearance of HCV viral load 24 weeks after the end of the treatment.
|
||
|
|||||||||
End point title |
Percentage of Participants With SVR 24 Weeks After end of Treatment [1] | ||||||||
End point description |
SVR was defined as a disappearance of HCV viral load 24 weeks after the end of the treatment. Intention-to-treat (ITT) Population defined as all enrolled participants who received at least 1 dose of study drug.
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
24 weeks after the end of treatment (72 weeks)
|
||||||||
| 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: Due to EudraCT limitation, it is not possible to provide statistical analysis for single arm. |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||||||
End point title |
Change From Baseline in Hemoglobin Level at Week 12 of Treatment Among Participants With or Without SVR [2] | ||||||||||||
End point description |
ITT Population.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Baseline and Week 12
|
||||||||||||
| 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 planned for this endpoint. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||||||||
End point title |
Number of Participants With Decrease in Hemoglobin | ||||||||||||||||||
End point description |
The drop in Hb level at Week 12 compared to level at baseline was assessed and categorized in pre-defined categories (up to 20, 20-40, >40 g/L) for the group of participants who achieved SVR and in the group of participants without SVR. ITT Population.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Week 12
|
||||||||||||||||||
|
|||||||||||||||||||
Statistical analysis title |
Number of Participants With Decrease in Hemoglobin | ||||||||||||||||||
Comparison groups |
Participants With SVR v Participants Without SVR
|
||||||||||||||||||
Number of subjects included in analysis |
30
|
||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||
P-value |
= 0.0867 | ||||||||||||||||||
Method |
Fisher exact | ||||||||||||||||||
Confidence interval |
|||||||||||||||||||
|
|||||||||||||
End point title |
Lowest Hemoglobin Level During Treatment Among Participants With or Without SVR | ||||||||||||
End point description |
The mean minimum hemoglobin value achieved during the treatment was assessed in the group of participants who achieved SVR and in the group of participants without SVR. ITT Population.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 12
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
||||||||||
End point title |
Number of Participants With Reduction in Ribavirin Dose Due to Drop in Hemoglobin Among Participants With or Without SVR | |||||||||
End point description |
Number of participants with reduction in ribavirin dose due to decrease in Hb level was assessed in the group of participants who achieved SVR and in the group of participants without SVR. ITT Population.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
Week 12
|
|||||||||
|
||||||||||
Statistical analysis title |
Participants With Reduction in Ribavirin Dose | |||||||||
Comparison groups |
Participants Without SVR v Participants With SVR
|
|||||||||
Number of subjects included in analysis |
30
|
|||||||||
Analysis specification |
Pre-specified
|
|||||||||
Analysis type |
superiority | |||||||||
P-value |
= 0.6492 | |||||||||
Method |
ANCOVA | |||||||||
Confidence interval |
||||||||||
|
||||||||||
End point title |
Number of Participants With Neutropenia Among Participants With or Without SVR | |||||||||
End point description |
ITT Population.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
Week 12
|
|||||||||
|
||||||||||
| No statistical analyses for this end point | ||||||||||
|
||||||||||
End point title |
Number of Participants With Thrombocytopenia Among Participants With or Without SVR | |||||||||
End point description |
ITT Population.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
Week 12
|
|||||||||
|
||||||||||
Statistical analysis title |
Participants With Thrombocytopenia by SVR Status | |||||||||
Comparison groups |
Participants With SVR v Participants Without SVR
|
|||||||||
Number of subjects included in analysis |
30
|
|||||||||
Analysis specification |
Pre-specified
|
|||||||||
Analysis type |
superiority | |||||||||
P-value |
= 0.0333 | |||||||||
Method |
Wilcoxon (Mann-Whitney) | |||||||||
Confidence interval |
||||||||||
|
|||||||||||||||||||||
|
Adverse events information
|
|||||||||||||||||||||
Timeframe for reporting adverse events |
From baseline up to 24 weeks after end of treatment (up to 72 weeks)
|
||||||||||||||||||||
Assessment type |
Non-systematic | ||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||
Dictionary version |
14.0
|
||||||||||||||||||||
|
Reporting groups
|
|||||||||||||||||||||
Reporting group title |
peginterferon alpha-2a + Ribavirin
|
||||||||||||||||||||
Reporting group description |
Participants infected with HCV genotype 1, who were either treatment naïve or failed to respond to previous combination therapy with interferon and ribavirin, were included in the study. These participants were treated with a combination therapy of peginterferon alpha-2a at a dose of 180 mcg subcutaneously once a week and ribavirin 1000-1200 mg by body weight (1000 mg if weight <75 kg; 1200 mg if weight >=75 kg) orally once daily in 2 divided doses, for a total of 48 weeks. | ||||||||||||||||||||
|
|||||||||||||||||||||
| 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 | |||
