Hepatitis B, ChronicPhase 4CAESARNCT01023217
Entecavir Plus Adefovir in Lamivudine-Resistant Chronic Hepatitis B Patients Who Fail Lamivudine Plus Adefovir
A Phase 4 study testing Adefovir, Entecavir and Lamivudine in people with Hepatitis B, Chronic, run by Asan Medical Center at 1 site in South Korea.
Trial summary
The presence of persistent inadequate or suboptimal virologic response is a strong risk factor for viral resistance and breakthrough and also for disease progression of chronic hepatitis B, and thus, a change in therapy is required. Read more about this study
- Who is it for?
- Ages 16 to 75 years
- Conditions the study is for
- Hepatitis B, Chronic
- What is being tested?
- Adefovir, Entecavir and Lamivudine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 1 siteSouth Korea
- Study dates
- Nov 2009to Sep 2012
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 16 to 75 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Male or female, 16 to 75 years of age
- Compensated liver disease(Child-Pugh class A)
- HBsAg positive at least 6 months or more
- HBeAg positive or negative
- Confirmation of Lamivudine-resistance HBV mutation anytime before the study
- Patients with suboptimal response (HBV DNA > 2000 IU/mL despite combination of Adefovir [10 mg/day] plus Lamivudine [100 mg/day] for 6 months or more). Serum HBV DNA should be determined by the PCR assay at the local laboratory at screening for this study
Show all 9Show fewer
- Patient is ambulatory.
- Patient is willing and able to comply with the study drug regimen and all other study requirements.
- The patient is willing and able to provide written informed consent to participate in the study.
Who cannot join
- Patient has a history of hepatocellular carcinoma (HCC) or findings suggestive of possible HCC, such as suspicious foci on imaging studies or elevated serum alpha fetoprotein (AFP) levels. In patients with such findings, HCC should be ruled-out prior to randomizing the patient for the present study.
- Patient previously received oral antiviral agent other than Lamivudine or Adefovir
- Patient has received interferon or other immunomodulatory treatment for HBV infection within 12 months before screening for this study.
- Patient has concomitant other chronic viral infection (HCV or HIV)
- Patient has evidence of renal insufficiency defined as serum creatinine > 1.5 mg/dL
- Patient has medical condition that requires use of systemic prednisolone or other immunosuppressive agent (including chemotherapeutic agent)
Show all 16Show fewer
- Patient is currently abusing alcohol or illicit drugs, or has a history of alcohol abuse or illicit substance abuse within the preceding two years.
- Patient is pregnant or breastfeeding or willing to be pregnant
- Patient has one or more additional known primary or secondary causes of liver disease, other than hepatitis B (e.g., alcoholism, autoimmune hepatitis, malignancy with hepatic involvement, hemochromatosis, alpha-1 antitrypsin deficiency, Wilson's Disease, other congenital or metabolic conditions affecting the liver, congestive heart failure or other severe cardiopulmonary disease, etc.).
- A history of treated malignancy (other than hepatocellular carcinoma) is allowable if the patient's malignancy has been in complete remission, off chemotherapy and without additional surgical intervention, during the preceding three years.
- Clinical signs of decompensated liver disease as indicated by any one of the following:
- serum bilirubin > 3 mg/dL
- prothrombin time > 6 seconds prolonged or INR >1.6
- serum albumin < 2.8 g/dL
- History of ascites, variceal hemorrhage, or hepatic encephalopathy
- Child-Pugh score ≥7
Trial locations and contacts
1 site in 1 country.
South Korea1 site
Asan Medical Center
Seoul, The Meteropolis of Seoul, 138-736
About this study
Official title: Continuation of Lamivudine Plus Adefovir Versus Switching to Entecavir Plus Adefovir in Adults With Chronic Hepatitis B Who Have Resistant Mutants to Lamivudine and Show Suboptimal Response to Combination of Lamivudine Plus Adefovir
The presence of persistent inadequate or suboptimal virologic response is a strong risk factor for viral resistance and breakthrough and also for disease progression of chronic hepatitis B, and thus, a change in therapy is required. The combination of entecavir (ETV) and adefovir (ADV) is a promising treatment for patients with lamivudine (LAM)-resistance who show suboptimal response to the combination of LAM and ADV.
In this randomized, open labeled trial,the investigators will compare the efficacy of continuation of ADV plus LAM versus switch to ADV plus ETV in adults with LAM-resistant chronic hepatitis B who shows suboptimal response to the combination treatment of ADV and LAM.
Read the detailed description
In this randomized, open label, two-arm, single center phase IV trial, the investigators will assess and compare the efficacy and safety of continuation of ADV plus LAM versus switching to ADV plus ETV up to 52-weeks in Korean adults with chronic hepatitis B who have resistant mutants to LAM and show suboptimal response to combination of ADV plus LAM.
All study subjects who complete the initial treatments of 52-weeks will be thereafter treated with the combination of ADV plus ETV for 52 more weeks.
Study period: Nov 2009 - October 2012 Patient enrollment period: November 2009 - December 2010
Study protocol
- Group A (ADV+LAM group): Adefovir (10 mg/day) + Lamivudine (100 mg/day) for 52 weeks, and thereafter, Adefovir (10 mg/day) + Entecavir (1 mg/day) for 52 more weeks
- Group B (ADV+ETV group): Adefovir (10 mg/day) + Entecavir (1 mg/day) for 104 weeks
- Conditions
- Hepatitis B, Chronic
- Being tested
- Adefovir, Entecavir, Lamivudine
- Keywords
- Chronic hepatitis B, lamivudine, adefovir, entecavir
- 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.
AdefovirDrug
Also called Adefovir dipivoxil (Hepsera)
Adefovir dipivoxil (Hepsera) 10 mg/day orally for 104 weeks
EntecavirDrug
Also called Entecavir (Baraclude)
Entecavir 1 mg/day orally
LamivudineDrug
Also called Lamivudine (Zeffix)
Lamivudine (Zeffix) 100 mg/day orally
| Study group | Role | What they receive |
|---|---|---|
| Adefovir plus Entecavir | Experimental | Adefovir + Entecavir for 104 weeks Receives: Drug: Adefovir; Drug: Entecavir |
| Adefovir plus Lamivudine | Active comparator | Adefovir + Lamivudine for 52 weeks, and thereafter, Adefovir + Entecavir for 52 more weeks Receives: Drug: Adefovir; Drug: Entecavir; Drug: Lamivudine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete Virologic Response (CVR, Serum HBV DNA Undetectable by PCR or Less Than 60 IU/mL)
Measured: at week 52 from randomization
Secondary outcomes (4)
Reduction in Serum HBV DNA Levels
Measured: at week 52 and at week 104 from randomization
Genotypic Resistance to ADV or ETV
Measured: at week 52 and at week 104 from randomization
Normalization of ALT Level
Measured: at week 52 and at week 104 from randomization
Complete Virologic Response (CVR, Serum HBV DNA Undetectable by PCR or Less Than 60 IU/mL)
Measured: at week 104 from randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Dec 2009 (estimated)
- Study startNov 2009
- Primary completionJul 2012
- Study completionSep 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hepatitis B, ChronicStudies of the same condition, open and under way.
- More trials run by Asan Medical CenterThe 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
- 90 participants (actual)
Sponsor and investigators
- Lead sponsor
- Asan Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Young-Suk Lim, Asan Medical Center
- Investigators
- Young-suk Lim, M.D.,Ph.D., Principal investigator, Asan Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01023217
- Sponsor's protocol ID
- AMC-2009-0536
- Acronym
- CAESAR
- Status last verified
- Jan 2014
- First submitted
- 1 Dec 2009
- Last updated
- 10 Feb 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Lim YS, Lee JY, Lee D, Shim JH, Lee HC, Lee YS, Suh DJ. Randomized trial of the virologic response during up to two years of entecavir-adefovir combination therapy in multiple-drug-refractory chronic hepatitis B virus patients. Antimicrob Agents Chemother. 2013 Jul;57(7):3369-74. doi: 10.1128/AAC.00587-13. Epub 2013 May 6.
PubMed 23650172
Study at a glance
From the registry record, last updated by the sponsor on 10 Feb 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Continuation of Lamivudine Plus Adefovir Versus Switching to Entecavir Plus Adefovir in Adults With Chronic Hepatitis B Who Have Resistant Mutants to Lamivudine and Show Suboptimal Response to Combination of Lamivudine Plus Adefovir
- ClinicalTrials.gov ID
- NCT01023217
- Acronym / sponsor ID
- CAESAR / AMC-2009-0536
- Conditions
- Hepatitis B, Chronic
- Keywords
- Chronic hepatitis B, lamivudine, adefovir, entecavir
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 90 participants (actual)
- Lead sponsor
- Asan Medical CenterUniversity, hospital or other
- Study start
- Nov 2009
- Primary completion
- Jul 2012 (actual)
- Study completion
- Sep 2012 (actual)
- First posted
- 2 Dec 2009 (estimated)
- Results
- Posted 13 Jan 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The presence of persistent inadequate or suboptimal virologic response is a strong risk factor for viral resistance and breakthrough and also for disease progression of chronic hepatitis B, and thus, a change in therapy is required. The combination of entecavir (ETV) and adefovir (ADV) is a promising treatment for patients with lamivudine (LAM)-resistance who show suboptimal response to the combination of LAM and ADV.
In this randomized, open labeled trial,the investigators will compare the efficacy of continuation of ADV plus LAM versus switch to ADV plus ETV in adults with LAM-resistant chronic hepatitis B who shows suboptimal response to the combination treatment of ADV and LAM.
Detailed description
In this randomized, open label, two-arm, single center phase IV trial, the investigators will assess and compare the efficacy and safety of continuation of ADV plus LAM versus switching to ADV plus ETV up to 52-weeks in Korean adults with chronic hepatitis B who have resistant mutants to LAM and show suboptimal response to combination of ADV plus LAM.
All study subjects who complete the initial treatments of 52-weeks will be thereafter treated with the combination of ADV plus ETV for 52 more weeks.
Study period: Nov 2009 - October 2012 Patient enrollment period: November 2009 - December 2010
Study protocol
- Group A (ADV+LAM group): Adefovir (10 mg/day) + Lamivudine (100 mg/day) for 52 weeks, and thereafter, Adefovir (10 mg/day) + Entecavir (1 mg/day) for 52 more weeks
- Group B (ADV+ETV group): Adefovir (10 mg/day) + Entecavir (1 mg/day) for 104 weeks
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Adefovir plus Entecavir | Experimental | Drug: Adefovir, Drug: EntecavirAdefovir + Entecavir for 104 weeks |
| Adefovir plus Lamivudine | Active comparator | Drug: Adefovir, Drug: Entecavir, Drug: LamivudineAdefovir + Lamivudine for 52 weeks, and thereafter, Adefovir + Entecavir for 52 more weeks |
Who may qualify
- Ages
- 16 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- Male or female, 16 to 75 years of age
- Compensated liver disease(Child-Pugh class A)
- HBsAg positive at least 6 months or more
- HBeAg positive or negative
- Confirmation of Lamivudine-resistance HBV mutation anytime before the study
Key exclusion criteria (16 listed)
- Patient has a history of hepatocellular carcinoma (HCC) or findings suggestive of possible HCC, such as suspicious foci on imaging studies or elevated serum alpha fetoprotein (AFP) levels. In patients with such findings, HCC should be ruled-out prior to randomizing the patient for the present study.
- Patient previously received oral antiviral agent other than Lamivudine or Adefovir
- Patient has received interferon or other immunomodulatory treatment for HBV infection within 12 months before screening for this study.
- Patient has concomitant other chronic viral infection (HCV or HIV)
- Patient has evidence of renal insufficiency defined as serum creatinine > 1.5 mg/dL
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 |
|---|---|---|
| AdefovirAlso: Adefovir dipivoxil (Hepsera)Adefovir dipivoxil (Hepsera) 10 mg/day orally for 104 weeks | Drug | Adefovir plus Entecavir, Adefovir plus Lamivudine |
| EntecavirAlso: Entecavir (Baraclude)Entecavir 1 mg/day orally | Drug | Adefovir plus Entecavir, Adefovir plus Lamivudine |
| LamivudineAlso: Lamivudine (Zeffix)Lamivudine (Zeffix) 100 mg/day orally | Drug | Adefovir plus Lamivudine |
Primary outcome
Complete Virologic Response (CVR, Serum HBV DNA Undetectable by PCR or Less Than 60 IU/mL)
Time frame: at week 52 from randomization
4 secondary outcomes
Reduction in Serum HBV DNA Levels
Time frame: at week 52 and at week 104 from randomization
Genotypic Resistance to ADV or ETV
Time frame: at week 52 and at week 104 from randomization
Normalization of ALT Level
Time frame: at week 52 and at week 104 from randomization
Complete Virologic Response (CVR, Serum HBV DNA Undetectable by PCR or Less Than 60 IU/mL)
Time frame: at week 104 from randomization
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Feb 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 23650172Lim YS, Lee JY, Lee D, Shim JH, Lee HC, Lee YS, Suh DJ. Randomized trial of the virologic response during up to two years of entecavir-adefovir combination therapy in multiple-drug-refractory chronic hepatitis B virus patients. Antimicrob Agents Chemother. 2013 Jul;57(7):3369-74. doi: 10.1128/AAC.00587-13. Epub 2013 May 6.
Related trials for Hepatitis B, Chronic
Active, not recruitingPhase 2
A Study of Sequential Therapy With Daplusiran/Tomligisiran (DAP/TOM) Followed by Bepirovirsen in Participants Living With Chronic Hepatitis B (CHB)
Chronic Hepatitis B Virus Infection, Hepatitis B
RecruitingObservational study
Evaluation of Patients With Liver Disease
Hepatitis D, Hepatitis C
Active, not recruitingPhase 2
Study of Bepirovirsen in Participants Living With Human Immunodeficiency Virus and Chronic Hepatitis B Virus Infection (B-Focus)
Hepatitis B
Active, not recruitingPhase 2
Long-term Follow-up Study to Evaluate Durability of Treatment Response in Previous Bepirovirsen Study Participants (B-Sure)
Hepatitis B
Enrolling by invitationPhase 1
A Phase I Clinical Trial of CPU-YL01 Injection in Patients With Chronic Hepatitis B.
Chronic Hepatitis B
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.
Young-suk Lim, M.D.,Ph.D. principal investigator
Asan Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Adefovir, Entecavir and Lamivudine in people with Hepatitis B, Chronic, run by Asan Medical Center at 1 site in South Korea.
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 9 inclusion and 16 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: finished, as of the sponsor's last update on 10 Feb 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
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?
Yes. Results are posted in the registry (first posted 13 Jan 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Complete Virologic Response (CVR, Serum HBV DNA Undetectable by PCR or Less Than 60 IU/mL) (time frame: at week 52 from randomization). 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 NCT01023217, 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 10 Feb 2014.