Ignite Creation Date:
2024-05-06 @ 1:33 AM
Last Modification Date:
2024-10-26 @ 11:05 AM
Study NCT ID:
NCT01833611
Status:
UNKNOWN
Last Update Posted:
2013-04-17
First Post:
2012-04-27
Brief Title:
Entecavir for Chronic Hepatitis B Patients With Persistently Normal ALT
Sponsor:
National Cheng-Kung University Hospital
Organization:
National Cheng-Kung University Hospital
Study Overview
Official Title:
Phase IV Study of the Efficacy of Entecavir in Patients With Chronic Hepatitis B Virus Infection and Persistently Normal Alanine Aminotransferase
Status:
UNKNOWN
Status Verified Date:
2013-04
Last Known Status:
ACTIVE_NOT_RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Entecavir ETV has shown superior ability to suppress hepatitis B virus HBV replication histology improvement as well as low rate of emergence of resistant mutants Out of range of clinical recommendations for treatment of chronic hepatitis B CHB chronic HBV carriers with persistently normal ALT and viral load more than 105 copiesmL have progression of liver disease during long-term follow-up In addition certain proportions of these patients do have significant inflammation and fibrosis in liver histology This study will be able to identify who are at risk of liver disease progression and evaluate efficacy of ETV regarding improvement of liver histology during short-term 1-year and long-term ETV treatment 3-year
Detailed Description:
TITLE A Randomized Double-blind Placebo-control Study Evaluating the Efficacy of Entecavir in Patients with Chronic Hepatitis B Virus Infection and Persistently Normal Alanine Aminotransferase INDICATION Chronic hepatitis B virus infection with persistently normal ALT
OBJECTIVES
Primary objective To evaluate the efficacy of entecavir ETV in improving liver histology in patients with chronic hepatitis B virus infection and persistently normal ALT
The primary endpoint is to compare the proportion of subjects in each treatment group who achieve the histologic Endpoint defined as improvement in the necroinflammatory score 2 point decrease in Knodell HAI score and no worsening of fibrosis 1 point increase in the Knodell fibrosis score at the Week 52 compared to baseline
Secondary objectives
To compare the proportion of subjects in each treatment group with the following objectives at week 52 week 104 and week 156 and post-dosing 24 weeks
1 Undetectable HBV DNA by the Roche TaqMan HBV Test limit of detection 60 IUmL HBV DNA by PCR will also be evaluated as a continuous parameter
2 The reduction of HBV DNA from baseline
STUDY DESIGN This is a 3-year prospective randomized double-blind placebo-control study Enrolled subjects will be allocated according to HBeAg status HBeAg-positive and HBeAg-negative then randomized to ETV or placebo group
ETV group 1st year ETV 05mg qd then open with ETV 05mg qd for 2nd 3rd year Placebo gr 1st year placebo then open with ETV 05mg for 2nd 3rd year
Dose of ETV 05 mgday Screening period 6 weeks Timing of liver biopsy baseline 52th week 156th week NUMBER OF PATIENTS 130 11
STUDY PERIOD NOV 2007 MAY 2011 DRUG ADMINISTRAITON Route oral Dose ETV 05 mgday Comparable placebo
STATISTICAL ANALYSIS Sample size determination
An evaluation of the efficacy of entecavir compared to placebo is planned A test for superiority of entecavir to placebo will be conducted that has high power to demonstrate superiority if there are larger histologic improvements of clinical importance Histologic improvement after one year is estimated as 50 of entecavir treatment and 25 of placebo Thus a sample size of 47 will be required for 90 of confidence level with 5 of error Finally we estimate that it will be appropriate to enroll 65 patients in each arm due to probably patients withdrawal
Statistical Analyses The difference in response rates for the Histologic Endpoint entecavir-placebo along with its standard error and 95 confidence interval will be computed Subset analyses defined by prognostic variables eg gender and HBV DNA level for the Histologic Endpoint will be performed
Change from baseline at Week 52 and 156 in Knodell Scores will also be summarized as a continuous parameter The secondary efficacy variables will also be summarized and compared between the treatment groups
OBJECTIVES
Primary objective To evaluate the efficacy of entecavir ETV in improving liver histology in patients with chronic hepatitis B virus infection and persistently normal ALT
The primary endpoint is to compare the proportion of subjects in each treatment group who achieve the histologic Endpoint defined as improvement in the necroinflammatory score 2 point decrease in Knodell HAI score and no worsening of fibrosis 1 point increase in the Knodell fibrosis score at the Week 52 compared to baseline
Secondary objectives
To compare the proportion of subjects in each treatment group with the following objectives at week 52 week 104 and week 156 and post-dosing 24 weeks
1 Undetectable HBV DNA by the Roche TaqMan HBV Test limit of detection 60 IUmL HBV DNA by PCR will also be evaluated as a continuous parameter
2 The reduction of HBV DNA from baseline
STUDY DESIGN This is a 3-year prospective randomized double-blind placebo-control study Enrolled subjects will be allocated according to HBeAg status HBeAg-positive and HBeAg-negative then randomized to ETV or placebo group
ETV group 1st year ETV 05mg qd then open with ETV 05mg qd for 2nd 3rd year Placebo gr 1st year placebo then open with ETV 05mg for 2nd 3rd year
Dose of ETV 05 mgday Screening period 6 weeks Timing of liver biopsy baseline 52th week 156th week NUMBER OF PATIENTS 130 11
STUDY PERIOD NOV 2007 MAY 2011 DRUG ADMINISTRAITON Route oral Dose ETV 05 mgday Comparable placebo
STATISTICAL ANALYSIS Sample size determination
An evaluation of the efficacy of entecavir compared to placebo is planned A test for superiority of entecavir to placebo will be conducted that has high power to demonstrate superiority if there are larger histologic improvements of clinical importance Histologic improvement after one year is estimated as 50 of entecavir treatment and 25 of placebo Thus a sample size of 47 will be required for 90 of confidence level with 5 of error Finally we estimate that it will be appropriate to enroll 65 patients in each arm due to probably patients withdrawal
Statistical Analyses The difference in response rates for the Histologic Endpoint entecavir-placebo along with its standard error and 95 confidence interval will be computed Subset analyses defined by prognostic variables eg gender and HBV DNA level for the Histologic Endpoint will be performed
Change from baseline at Week 52 and 156 in Knodell Scores will also be summarized as a continuous parameter The secondary efficacy variables will also be summarized and compared between the treatment groups
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None