- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01597934
Antiviral Efficacy of Switching to ETV Plus TDF
A Randomized, Multicenter, Prospective Study to Compare Antiviral Efficacy and Safety of Switching to ETV Plus TDF Versus Maintaining LAM/LDT Plus ADF Combination in CHC With PVR to LAM/LDF Plus ADF Combination Rescue Therapy for YMDD Mutation
Switching to Entecavir(ETV) plus Tenofovir Disoproxil Fumarate(TDF) combination will result in faster and greater antiviral activity and lower rates of resistance emergence over maintaining Lamivudine(LAM)/Telbivudine(LdT)+Adefovir(ADV) combination in partial responders to LAM/LdT+ADV rescue therapy.
Earlier switching to combination with the most potent regimen will be more effective to achieve virologic response(VR) and prevent further resistance emergence.
All subjects will orally take assigned drugs once daily for 48 weeks. All subjects will be assessed at baseline and every three months thereafter. Evaluations at each visit will include vital signs, physical examinations, laboratory tests, HBV DNA levels and adverse events. At baseline and every six months thereafter, serum will be assayed for HBV serology. Genotypic analysis will be performed at baseline and 48 weeks.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
- As TDF has not been approved yet in Korea, current KASL practice guideline generally recommends to add ADV in LAM-resistant or LdT-resistant patients.
- However, several local literatures reported a substantial proportion of patients treated with LAM plus ADV combination therapy showed a persistently inadequate or partial virologic response('VR') and YMDDm still maintained in spite of under rescue combination therapy.
- Due to the unavailability of TDF in Korea, ETV plus ADV combination has being considered a better salvage therapy with non-overlapping cross-resistance profiles in pts who fail to LAM plus ADV rescue therapy and local report demonstrated that the rate of VR was significantly higher with ETV+ADV switching group than LAM+ADV continuation group in partial responder to LAM plus ADV combination rescue therapy for LAM resistance.
- Hence, more earlier combination therapy with the most potent Nucleoside and Nucleotide analogue would be a promising salvage treatment for previous NA treatment failures but comparative prospective trials are limited.
- Therefore, this study will investigate the greater effectiveness and safety of switching to the most potent combination versus maintaining LAM(or LdT) plus ADV and also compare the rate of VR based on the HBV DNA cut-off level at switching - more than and less than 20,000 IU/mL.
All subjects will orally take assigned drugs once daily for 48 weeks. All subjects will be assessed at baseline and every three months thereafter. Evaluations at each visit will include vital signs, physical examinations, laboratory tests, HBV DNA levels and adverse events. At baseline and every six months thereafter, serum will be assayed for HBV serology. Genotypic analysis will be performed at baseline and 48 weeks.
Study Type
Enrollment (Anticipated)
Phase
- Phase 4
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- ≥ 20 years of age
- History of HBsAg positive for more than 6 months
- History of genotypic resistance to LAM or LdT (YMDDm)
- Partial responder (HBV DNA ≥ 60 IU/mL) currently receiving antiviral combination rescue therapy for at least 24 weeks of treatment with LAM+ADV or LdT+ADV
- Hepatitis B e Antigen(HBeAg)-positive and -negative
- Compensated liver disease (Child-Pugh A)
- Signed written informed consent after being instructed about the objective and procedure of the clinical study
Exclusion Criteria:
- History of genotypic resistance to ADV
- Most previous treatment of other than LAM+ADV and LdT+ADV
- Subjects with Alanine Aminotransferase(ALT) > 10xUpper Limit of normal(ULN)
- Co-infected with hepatitis C virus(HCV) or HIV
- Pregnant or lactating woman
- Subject who needs long-term administration of drugs including immunosuppressive agents, agents related to high risk in the hepatic/renal toxicity, agents influencing renal excretion
- History of liver transplantation or planned for liver transplantation
- Subject who was diagnosed malignant tumor and has been receiving chemotherapy
- Subject who has HCC history or who shows potential hepatocellular carcinoma (HCC) finding such as suspicious region in the radiologic exam(abdominal US or CT) or serum Alpha Feto Protein(AFP) elevation
- Renal Insufficiency (CLcr < 50ml/min based on Cockcroft-Gault equation considering weight, ages and serum creatinine)
- Subject who has a liver disease other than chronic hepatitis B (e.g. hemochromatosis, Wilson's disease, alcoholic liver disease, nonalcoholic fatty liver disease, alpha 1-antitrypsin deficiency etc.)
- Subject who has a history of hypersensitivity to study drug or its ingredients
- Subject who is involved in other clinical trial within 60 days prior to study entry
- Subject who the investigator deems inappropriate to participate in this study
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Group A:
Maintaining LAM/LdT+ADV combination Lamivudine 100mg / Telbivudine 600mg +Adefovir 10mg
|
Maintaining LAM/LdT+ADV combination Lamivudine 100mg / Telbivudine 600mg +Adefovir 10mg
Other Names:
|
Experimental: Group B
Switching to ETV plus TDF combination Entecavir 1.0mg + Tenofovir 300mg
|
Switching to ETV plus TDF combination Entecavir 1.0mg + Tenofovir 300mg
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The proportion of subjects who achieve virologic response(HBV DNA < 60 IU/mL, approximately 300 copies/mL) by real-time PCR at Week 48
Time Frame: at Week 48
|
To compare the proportion of subjects who achieve virologic response(HBV DNA < 60 IU/mL, approximately 300 copies/mL) in switching group(Entecavir plus Tenofovir) with that in maintaining group(Lamivudine/Telbivudine plus Adefovir) by real-time Polymerase chain reaction(PCR) at Week 48
|
at Week 48
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Virologic efficacy
Time Frame: Week 12, 24, 36, and 48
|
To compare virologic response in switching group(Entecavir plus Tenofovir) with those in maintaining group (Lamivudine/Telbivudine plus Adefovir) at Week 48
|
Week 12, 24, 36, and 48
|
serologic efficacy
Time Frame: Week 12, 24, 36, and 48
|
To compare serologic response in switching group(Entecavir plus Tenofovir) with those in maintaining group (Lamivudine/Telbivudine plus Adefovir) at Week 48
|
Week 12, 24, 36, and 48
|
biochemical efficacy
Time Frame: Week 12, 24, 36, and 48
|
To compare biochemical response in switching group(Entecavir plus Tenofovir) with those in maintaining group (Lamivudine/Telbivudine plus Adefovir) at Week 48
|
Week 12, 24, 36, and 48
|
Safety issue
Time Frame: Week 12, 24, 36, and 48
|
To compare safety issue in switching group(Entecavir plus Tenofovir) with those in maintaining group (Lamivudine/Telbivudine plus Adefovir) at Week 48 - severity of adverse event
|
Week 12, 24, 36, and 48
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Sang Hoon Ahn, MD, PhD, Yonsei University
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Anticipated)
Study Completion (Anticipated)
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
Additional Relevant MeSH Terms
- Digestive System Diseases
- Virus Diseases
- Infections
- Blood-Borne Infections
- Communicable Diseases
- Liver Diseases
- Hepatitis, Viral, Human
- Hepadnaviridae Infections
- DNA Virus Infections
- Hepatitis B
- Hepatitis
- Hepatitis B, Chronic
- Hepatitis, Chronic
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Reverse Transcriptase Inhibitors
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Anti-HIV Agents
- Anti-Retroviral Agents
- Tenofovir
- Entecavir
- Lamivudine
- Telbivudine
- Adefovir
- Adefovir dipivoxil
Other Study ID Numbers
- AI463-274
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 Chronic Hepatitis B
-
The Affiliated Nanjing Drum Tower Hospital of Nanjing...Gilead SciencesNot yet recruiting
-
Tongji HospitalGilead SciencesRecruiting
-
Jiangsu HengRui Medicine Co., Ltd.Unknown
-
Changhai HospitalCompleted
-
Zhongshan Hospital Xiamen UniversityUnknownHealthy | Chronic Hepatitis B InfectionChina
-
Tongji HospitalChia Tai Tianqing Pharmaceutical Group Co., Ltd.UnknownChronic Hepatitis b
-
Brii Biosciences LimitedVir Biotechnology, Inc.Active, not recruitingChronic Hepatitis B Virus InfectionSingapore, Thailand, Australia, China, Korea, Republic of
-
Nanfang Hospital of Southern Medical UniversityRecruiting
-
IlDong Pharmaceutical Co LtdRecruitingChronic Hepatitis bKorea, Republic of
-
Antios Therapeutics, IncTerminatedChronic Hepatitis bUnited States
Clinical Trials on Group A (Zeffix, Sebivo, Hepsera)
-
National Taiwan University HospitalTerminatedHBsAg-positive Renal Allograft Recipients
-
Novartis PharmaceuticalsCompleted
-
Taipei Veterans General Hospital, TaiwanChina Medical University Hospital; Kaohsiung Medical University Chung-Ho Memorial... and other collaboratorsUnknown
-
Inje UniversityBukwang PharmaceuticalTerminatedChronic Hepatitis BKorea, Republic of
-
National Health Research Institutes, TaiwanNational Taiwan University Hospital; Mackay Memorial Hospital; Chang Gung Memorial... and other collaboratorsTerminatedHepatocellular CarcinomaTaiwan
-
Keimyung University Dongsan Medical CenterPusan National University Hospital; Daegu Catholic University Medical Center; Kyungpook National University Hospital and other collaboratorsCompletedChronic Hepatitis BKorea, Republic of
-
Asan Medical CenterCompletedHepatitis B, ChronicKorea, Republic of
-
Korea UniversityGlaxoSmithKlineCompletedChronic Hepatitis BKorea, Republic of
-
University of UlmNovartisWithdrawn
-
Riphah International UniversityRecruitingHemiplegic Cerebral PalsyPakistan