- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01323452
Entecavir for Chronic Hepatitis B
The Antiviral Efficacy of Entecavir in Chronic Hepatitis B Within the European Network of Excellence (VIRGIL)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Chronic hepatitis B is a major health problem, affecting more than 350 million people worldwide. (1) First line treatment consists of pegylated IFN once weekly or oral nucleos(t)ide analogues (NA) once daily. (2) NA target the reverse transcriptase of hepatitis B virus (HBV), and are potent inhibitors of viral replication. In the absence of antiviral drug resistance, continued NA therapy is able to suppress viral replication over prolonged periods, and can prevent clinical progression to liver cirrhosis and hepatocellular carcinoma. (3) Currently approved agents include the nucleoside analogues lamivudine (LAM), telbivudine (LdT), and entecavir (ETV), and the nucleotide analogues adefovir dipivoxil (ADV), and tenofovir disiproxil fumarate (TDF).
Entecavir ETV is a cyclopentyl guanosine analogue, and a potent and selective inhibitor of HBV replication in vitro.(4) In the phase III registration trials it resulted in superior virologic, biochemical and histological efficacy after one year of therapy compared to LAM in both HBeAg-positive and HBeAg-negative chronic HBV patients. (5, 6) Moreover, ETV proved to have a high genetic barrier to resistance with only 1.2% of NA-naïve HBV patients demonstrating genotypic resistance to ETV after five years of ETV monotherapy.(7) In LAM-refractory chronic HBV patients ETV appeared to be less potent and the frequency of resistance was increased. (8, 9) After five years of treatment 51% of LAM-refractory patients showed genotypic ETV resistance, and in 43% a virologic breakthrough was observed as well. (7) Recently we presented the promising results of a large European cohort of patients treated with ETV for a median period of 12 months. We concluded that ETV should not be used in patients with a prior history of LAM-resistance. However, prior treatment with ADV did not influence the efficacy of ETV in these patients.(10)
HBeAg loss or seroconversion In HBeAg positive patients, HBeAg loss or seroconversion is the major objective of NA treatment regimes according to current guidelines. HBeAg loss or seroconversion is usually associated with sustained remission and a very low risk for the development of cirrhosis and hepatocellular carcinoma. (11-13) PEG-IFN induced HBeAg seroconversion was shown to be sustained in 70% after a 3 year follow up. (14) There are some contradictory results concerning NA induced durability of HBeAg loss or seroconversion. First reports on lamuvidine induced HBeAg loss or seroconversion were rather promising.(15-17) However, more recent and also larger studies report much higher relapse rates and predictors of sustainability were proposed. (18-21) The registration trial of entecavir showed a 82% durability after 24 weeks without consolidation therapy.(6) Recently we showed that the durability of HBeAg seroconversion was very poor with 42%, 58% and 74% seroreversion respectively 1,2 and 3 years after seroconversion on different NA treatment regimes. However, only a minority of these patients was treated with the newer and more potent NA. (22)
As the increasing number of patients who experienced treatment failure to different NA treatment regimens poses a growing problem for the clinician, data on the efficacy of ETV in these NA-experienced patient groups is warranted. Furthermore, current guidelines are subject of discussion as durability of NA induced HBeAg loss or seroconversion seems less sustained then expected, and prolonged or maybe infinite therapy may be necessary to prevent long term complications.
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
-
-
-
Rotterdam, Netherlands, 3015 CE
- Erasmus MC
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria:
- HBsAg positive for at least 6 months
- Entecavir therapy for at least 3 months
Exclusion Criteria:
- viral co infections
- concomitant antiviral therapy
Study Plan
How is the study designed?
Design Details
- Observational Models: Cohort
- Time Perspectives: Retrospective
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
Chronic HBV patients
Patients with chronic hepatitis B Treated for at least 3 months No HIV, HCV or HDV.
|
once daily
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Virological response
Time Frame: 144 weeks after starting Entecavir
|
Cumulative probability (%) of patients achieving HBV DNA negativity at week 144
|
144 weeks after starting Entecavir
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Harry LA Janssen, MD, PhD, Erasmus MC
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Digestive System Diseases
- RNA Virus Infections
- Virus Diseases
- Infections
- Blood-Borne Infections
- Communicable Diseases
- Liver Diseases
- Hepatitis, Viral, Human
- Hepadnaviridae Infections
- DNA Virus Infections
- Enterovirus Infections
- Picornaviridae Infections
- Hepatitis B
- Hepatitis
- Hepatitis A
- Hepatitis B, Chronic
- Hepatitis, Chronic
- Anti-Infective Agents
- Antiviral Agents
- Entecavir
Other Study ID Numbers
- VIRGIL
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Entecavir for Chronic Hepatitis B Patients
-
The 458 Hospital of Chinese PLAGuangzhou Baidi Biotechnology Co., Ltd; Guangzhou Pharmaceucal Company LimitedUnknownChronic Hepatitis B Patients With HBeAg-positiveChina
-
Beijing Friendship HospitalNot yet recruiting
-
Sohag UniversityRecruitingChronic Hepatitis b PatientsEgypt
-
Fuzhou General HospitalRecruitingChronic Hepatitis B Patients With a Normal ALT Level and Low ViremiaChina
-
Lai WeiActive, not recruitingTo Evaluate the Safety and Efficacy of Celecoxib Plus Nucleos(t)Ide Analogues in Nucleos(t)Ide-treated Patients With Chronic Hepatitis BChina
-
Uijeongbu St. Mary HospitalUnknownProportion of Patients With a Sustained Virological Response (Serum HBV DNA <20 IU/mL) at Week 48Korea, Republic of
-
Uijeongbu St. Mary HospitalUnknownProportion of Patients With a Sustained Virological Response (Serum HBV DNA <20 IU/mL) at Week 48
-
Tongji HospitalGilead SciencesRecruiting
-
Jiangsu HengRui Medicine Co., Ltd.Unknown
-
Changhai HospitalCompleted
Clinical Trials on Entecavir
-
Sunshine Lake Pharma Co., Ltd.Terminated
-
ShuGuang HospitalBeijing YouAn Hospital; Beijing Ditan Hospital; Shanghai Zhongshan Hospital; Tongji... and other collaboratorsUnknownLiver Cirrhosis Due to Hepatitis B VirusChina
-
Beijing Friendship HospitalPeking University; Peking University First Hospital; Peking University People... and other collaboratorsCompleted
-
Taipei Veterans General Hospital, TaiwanBristol-Myers SquibbCompletedProphylactic Use of Entecavir for Non-Hodgkin's Lymphoma Patients With Resolved Hepatitis B (HBVNHL)Hepatitis B | Non Hodgkin's LymphomaTaiwan
-
ShuGuang HospitalShanghai Zhongshan Hospital; Ruijin Hospital; Shanghai Public Health Clinical... and other collaboratorsUnknown
-
Beijing Friendship HospitalPeking University; Peking University First Hospital; Peking University People... and other collaboratorsCompleted
-
Peking UniversityUnknown
-
National Taiwan University HospitalUnknownHBV/HCV Co-infectionTaiwan
-
Beijing Continent Pharmaceutical Co, Ltd.Completed
-
Sun Yat-sen UniversityUnknown