Chronic Hepatitis BPhase 4NCT01597934
Antiviral Efficacy of Switching to ETV Plus TDF
A Phase 4 study testing Group A (Zeffix, Sebivo, Hepsera) and Group B (Baraclude, Viread) in people with Chronic Hepatitis B, run by Yonsei University.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Chronic Hepatitis B
- What is being tested?
- Group A (Zeffix, Sebivo, Hepsera) and Group B (Baraclude, Viread)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 104 participants
- Where
- No sites listed yet
- Study dates
- Aug 2012to May 2014
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ≥ 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
Who cannot join
- 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
Show all 14Show fewer
- 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
About this study
Official title: 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.
Read the 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.
- Conditions
- Chronic Hepatitis B
- Being tested
- Group A (Zeffix, Sebivo, Hepsera), Group B (Baraclude, Viread)
- Keywords
- Chronic hepatitis B, Partial virologic response, YMDD mutation
- Medical subject headings
- Hepatitis B, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Group A (Zeffix, Sebivo, Hepsera)Drug
Also called Zeffix, Sebivo, Hepsera
Maintaining LAM/LdT+ADV combination Lamivudine 100mg / Telbivudine 600mg +Adefovir 10mg
Group B (Baraclude, Viread)Drug
Also called Baraclude, Viread
Switching to ETV plus TDF combination Entecavir 1.0mg + Tenofovir 300mg
| Study group | Role | What they receive |
|---|---|---|
| Group A: | Active comparator | Maintaining LAM/LdT+ADV combination Lamivudine 100mg / Telbivudine 600mg +Adefovir 10mg Receives: Drug: Group A (Zeffix, Sebivo, Hepsera) |
| Group B | Experimental | Switching to ETV plus TDF combination Entecavir 1.0mg + Tenofovir 300mg Receives: Drug: Group B (Baraclude, Viread) |
What is being measured
The primary outcome is the main question the study is designed to answer.
The proportion of subjects who achieve virologic response(HBV DNA < 60 IU/mL, approximately 300 copies/mL) by real-time PCR 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
Measured: at Week 48
Secondary outcomes (4)
Virologic efficacy
To compare virologic response in switching group(Entecavir plus Tenofovir) with those in maintaining group (Lamivudine/Telbivudine plus Adefovir) at Week 48
Measured: Week 12, 24, 36, and 48
serologic efficacy
To compare serologic response in switching group(Entecavir plus Tenofovir) with those in maintaining group (Lamivudine/Telbivudine plus Adefovir) at Week 48
Measured: Week 12, 24, 36, and 48
biochemical efficacy
To compare biochemical response in switching group(Entecavir plus Tenofovir) with those in maintaining group (Lamivudine/Telbivudine plus Adefovir) at Week 48
Measured: Week 12, 24, 36, and 48
Safety issue
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
Measured: Week 12, 24, 36, and 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 May 2012 (estimated)
- Study startAug 2012
- Primary completionMay 2014 (estimated)
- Study completionMay 2014 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic Hepatitis BStudies of the same condition, open and under way.
- More trials run by Yonsei UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 104 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Yonsei University
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb, Seoul St. Mary's Hospital, The Catholic University of Korea, Soonchunhyang University Hospital, Pusan National University Hospital, Kyungpook National University Hospital, Hallym University Medical Center, Chonbuk National University Hospital
- Responsible party
- Principal investigator, Sang Hoon Ahn, Yonsei University
- Investigators
- Sang Hoon Ahn, MD, PhD, Principal investigator, Yonsei University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01597934
- Sponsor's protocol ID
- AI463-274
- Status last verified
- Jan 2014
- First submitted
- 8 May 2012
- Last updated
- 31 Jan 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Woo HY, Park JY, Bae SH, Kim CW, Jang JY, Tak WY, Kim DJ, Kim IH, Heo J, Ahn SH. Entecavir+tenofovir vs. lamivudine/telbivudine+adefovir in chronic hepatitis B patients with prior suboptimal response. Clin Mol Hepatol. 2020 Jul;26(3):352-363. doi: 10.3350/cmh.2019.0044n. Epub 2020 May 28.
PubMed 32460460
Study at a glance
From the registry record, last updated by the sponsor on 31 Jan 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT01597934
- Acronym / sponsor ID
- AI463-274
- Conditions
- Chronic Hepatitis B
- Keywords
- Chronic hepatitis B, Partial virologic response, YMDD mutation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 104 participants (estimated)
- Lead sponsor
- Yonsei UniversityUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb, Seoul St. Mary's Hospital, The Catholic University of Korea, Soonchunhyang University Hospital, Pusan National University Hospital, Kyungpook National University Hospital, Hallym University Medical Center, Chonbuk National University Hospital
- Study start
- Aug 2012
- Primary completion
- May 2014 (estimated)
- Study completion
- May 2014 (estimated)
- First posted
- 15 May 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group A: | Active comparator | Drug: Group A (Zeffix, Sebivo, Hepsera)Maintaining LAM/LdT+ADV combination Lamivudine 100mg / Telbivudine 600mg +Adefovir 10mg |
| Group B | Experimental | Drug: Group B (Baraclude, Viread)Switching to ETV plus TDF combination Entecavir 1.0mg + Tenofovir 300mg |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- ≥ 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
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Group A (Zeffix, Sebivo, Hepsera)Also: Zeffix, Sebivo, HepseraMaintaining LAM/LdT+ADV combination Lamivudine 100mg / Telbivudine 600mg +Adefovir 10mg | Drug | Group A: |
| Group B (Baraclude, Viread)Also: Baraclude, VireadSwitching to ETV plus TDF combination Entecavir 1.0mg + Tenofovir 300mg | Drug | Group B |
Primary outcome
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
4 secondary outcomes
Virologic efficacy
Time frame: Week 12, 24, 36, and 48
serologic efficacy
Time frame: Week 12, 24, 36, and 48
biochemical efficacy
Time frame: Week 12, 24, 36, and 48
Safety issue
Time frame: Week 12, 24, 36, and 48
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jan 2014.
- Derived from this study: PubMed 32460460Woo HY, Park JY, Bae SH, Kim CW, Jang JY, Tak WY, Kim DJ, Kim IH, Heo J, Ahn SH. Entecavir+tenofovir vs. lamivudine/telbivudine+adefovir in chronic hepatitis B patients with prior suboptimal response. Clin Mol Hepatol. 2020 Jul;26(3):352-363. doi: 10.3350/cmh.2019.0044n. Epub 2020 May 28.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sang Hoon Ahn, MD, PhD principal investigator
Yonsei University
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Group A (Zeffix, Sebivo, Hepsera) and Group B (Baraclude, Viread) in people with Chronic Hepatitis B, run by Yonsei University.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 31 Jan 2014. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01597934, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jan 2014.