Chronic Hepatitis BPhase 4NCT01595633
Switch From Adefovir to Tenofovir in Chronic Hepatitis B for Suboptimal Response to Adefovir-based Combination Therapy
A Phase 4 study testing Switching from adefovir (10mg/day) to tenofovir (300mg/day) in people with Chronic Hepatitis B, run by Yonsei University at 1 site in South Korea.
Trial summary
In Korea, the number of suboptimal responders to rescue combination therapy is also increasing. As a matter of fact, according to the investigations in Korea, HBV DNA undetectability at 48 weeks of adefovir and lamivudine combination rescue therapy for patients with lamivudine resistance was reported to be only 32.4%… 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?
- Switching from adefovir (10mg/day) to tenofovir (300mg/day)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 124 participants
- Where
- 1 siteSouth Korea
- Study dates
- Mar 2012to Feb 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
- subjects with age >= 20 years
- subjects with chronic hepatitis B
- subjects treated with nucleoside analogues plus adefovir for at least 6 months due to resistance to nucleoside analogues (Lamivudine, Telbivudine, Entecavir, or Clevudine)
- subjects with partial virologic response to nucleoside analogues plus adefovir HBV DNA ≥ 60 IU/mL)
- subjects with ALT less than 5 times of upper limit of normal
- subjects who agreed to participate in the clinical trials and signed the informed consents
Who cannot join
- subjects with decompensate liver cirrhosis Child-Pugh B, C)
- subjects with Adefovir mutation
- subjects with HCV, HDV, or HIV infection
- pregnant or lactating women
- women of childbearing age who do not use the appropriate contraception method
- subjects who have the abnormal lesion suspected of hepatocellular carcinoma on imaging modalities
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- subjects with other liver diseases such as hemochromatosis, Wilson's disease, alcoholic liver disease, nonalcoholic liver disease, alpha-1 antitrypsin deficiency
- subjects with hypersensitivity for study drugs
- subjects who participated in other clinical trials 60 days before the current recruitment
- subjects who are judged as inappropriate by investigators
Trial locations and contacts
1 site in 1 country.
South Korea1 site, 1 recruiting
- Recruiting
Department of Internal Medicine, Yonsei University College of Medicine
Seoul, 120-752
BeomKyung Kim, Dr, +82-2-2228-1930, beomkkim@yuhs.ac
Jun Yong Park, Dr, +82-2-2228-1994, DRPJY@yuhs.ac
About this study
Official title: Randomized Study Comparing Nucleoside Analogues Plus Tenofovir and Nucleoside Analogues Plus Adefovir in Chronic Hepatitis B Patients With Suboptimal Response to Adefovir-based Combination Therapy Due to Nucleoside Analogues Resistance
In Korea, the number of suboptimal responders to rescue combination therapy is also increasing. As a matter of fact, according to the investigations in Korea, HBV DNA undetectability at 48 weeks of adefovir and lamivudine combination rescue therapy for patients with lamivudine resistance was reported to be only 32.4%, which suggested that the appropriate another rescue therapy might be urgently required. However, there is no promising oral antiviral agents to control these patients in Asia-Pacific region, where tenofovir is not widely available. Tenofovir has a higher potent antiviral efficacy and a negligible drug resistance rate. The switch from adefovir to tenofovir in patients who have insufficient hepatitis B virus (HBV) suppression (HBV DNA ≥ 60 IU/mL by PCR) may lead to increased viral suppression or more HBeAg loss/seroconversion.
Here, the investigators aimed to conduct a randomized study on evaluating the antiviral efficacy, safety, and tolerability of switching from adefovir to tenofovir in chronic hepatitis B patients who have suboptimal response to adefovir-based combination rescue therapy due to nucleoside analogues Resistance (SATIS study).
Read the detailed description
The major goal of antiviral therapy against chronic hepatitis B is to suppress viral replications successfully, ultimately preventing the chronic liver damage, development of liver cirrhosis and hepatocellular carcinoma. In Korea, the number of multi-drug resistant CHB has been rapidly increased last few years. It is because that the national health insurance coverage is very limited for the patients who experienced primary treatment failure. The only switch to adefovir has been allowed in lamivudine resistant patients and thus this sequential rescue therapy generated multi-drug resistance to both adefovir and another drugs. Thus, nowadays, add-on therapy rather than switch therapy might be preferred from major guidelines in this point.
However, the number of suboptimal responders to rescue combination therapy is also increasing. As a matter of fact, according to the investigations in Korea, HBV DNA undetectability at 48 weeks of adefovir and lamivudine combination rescue therapy for patients with lamivudine resistance was reported to be only 32.4%, which suggested that the appropriate another rescue therapy might be urgently required. However, there is no promising oral antiviral agents to control these patients in Asia-Pacific region, where tenofovir is not widely available. Tenofovir has a higher potent antiviral efficacy and a negligible drug resistance rate. It belongs to the different class compared to other oral nucleoside analogues (NAs) such as lamivudine, telbivudine, clevudine and entecavir. The switch from adefovir to tenofovir in patients who have insufficient hepatitis B virus (HBV) suppression (HBV DNA ≥ 60 IU/mL by PCR) may lead to increased viral suppression or more HBeAg loss/seroconversion. The results of this study will provide a rationale for switch from adefovir to tenofovir in combination to another drug continued (lamivudine, telbivudine, clevudine and entecavir).
Here, the investigators aimed to conduct a randomized study on evaluating the antiviral efficacy, safety, and tolerability of switching from adefovir to tenofovir in chronic hepatitis B patients who have suboptimal response to adefovir-based combination rescue therapy due to nucleoside analogues Resistance (SATIS study).
- Conditions
- Chronic Hepatitis B
- Being tested
- Switching from adefovir (10mg/day) to tenofovir (300mg/day)
- Keywords
- nucleoside analogue, adefovir, tenofovir, hepatitis B
- Medical subject headings
- Hepatitis B, Chronic, Hepatitis B
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Switching from adefovir (10mg/day) to tenofovir (300mg/day)Drug
active comparator: Nucleoside analogues (Lamivudine 100mg, Telbivudine 600mg, Entecavir 1mg, or Clevudine 30mg/day) + Adefovir 10mg/day Experimental: Nucleoside analogues (Lamivudine 100mg, Telbivudine 600mg, Entecavir 1mg, or Clevudine 30mg/day) + Tenofovir 300mg/day
| Study group | Role | What they receive |
|---|---|---|
| Adefovir, nucleoside analogues | Active comparator | Nucleoside analogues (Lamivudine 100mg, Telbivudine 600mg, Entecavir 1mg, or Clevudine 30mg) + Adefovir 10mg Receives: Drug: Switching from adefovir (10mg/day) to tenofovir (300mg/day) |
| Tenofovir, nucleoside analogues | Experimental | Nucleoside analogues (Lamivudine 100mg, Telbivudine 600mg, Entecavir 1mg, or Clevudine 30mg) + Tenofovir 300mg Receives: Drug: Switching from adefovir (10mg/day) to tenofovir (300mg/day) |
What is being measured
The primary outcome is the main question the study is designed to answer.
number of patients with complete virologic response (HBV DNA < 60 IU/mL, approximately 300 copies/mL) at 48 weeks treatment
Complete virologic response (HBV DNA < 60 IU/mL, approximately 300 copies/mL) at 48 weeks treatment
Measured: 48 weeks
Secondary outcomes (5)
number of patients with antiviral response at 48 weeks therapy
number of patients with antiviral response (defined as decrement of HBV DNA level with 2 Log from baseline) at 48 weeks therapy
Measured: 48 weeks
number of patients with biochemical response at 48 weeks therapy
number of patients with biochemical response (defined as ALT normalization) at 48 weeks therapy
Measured: 48 weeks
number of patients with serologic response at 48 weeks therapy
number of patients with serologic response (defined as HBeAg seroconversion in case of HBeAg-positive hepatitis) at 48 weeks therapy
Measured: 48 weeks
number of patients with appearance of resistant mutant strain at 48 weeks
number of patients with appearance of resistant mutant strain at 48 weeks
Measured: 48 weeks
Number of Participants with Adverse Events
Number of Participants with Adverse Events during treatments (Adverse effects will be monitored every visit using physical examination and routine blood chemistry tests.)
Measured: 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 May 2012 (estimated)
- Study startMar 2012
- Primary completionFeb 2014 (estimated)
- Study completionFeb 2014 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- 124 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Yonsei University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Sang Hoon Ahn, Yonsei University
- Investigators
- Sang Hoon Ahn, MD, PhD., Principal investigator, Department of Internal Medicine, Yonsei University College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01595633
- Sponsor's protocol ID
- 4-2011-0937
- Status last verified
- May 2012
- First submitted
- 11 Mar 2012
- Last updated
- 10 May 2012
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 10 May 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Study Comparing Nucleoside Analogues Plus Tenofovir and Nucleoside Analogues Plus Adefovir in Chronic Hepatitis B Patients With Suboptimal Response to Adefovir-based Combination Therapy Due to Nucleoside Analogues Resistance
- ClinicalTrials.gov ID
- NCT01595633
- Acronym / sponsor ID
- 4-2011-0937
- Conditions
- Chronic Hepatitis B
- Keywords
- nucleoside analogue, adefovir, tenofovir, hepatitis B
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 124 participants (estimated)
- Lead sponsor
- Yonsei UniversityUniversity, hospital or other
- Study start
- Mar 2012
- Primary completion
- Feb 2014 (estimated)
- Study completion
- Feb 2014 (estimated)
- First posted
- 10 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.
In Korea, the number of suboptimal responders to rescue combination therapy is also increasing. As a matter of fact, according to the investigations in Korea, HBV DNA undetectability at 48 weeks of adefovir and lamivudine combination rescue therapy for patients with lamivudine resistance was reported to be only 32.4%, which suggested that the appropriate another rescue therapy might be urgently required. However, there is no promising oral antiviral agents to control these patients in Asia-Pacific region, where tenofovir is not widely available. Tenofovir has a higher potent antiviral efficacy and a negligible drug resistance rate. The switch from adefovir to tenofovir in patients who have insufficient hepatitis B virus (HBV) suppression (HBV DNA ≥ 60 IU/mL by PCR) may lead to increased viral suppression or more HBeAg loss/seroconversion.
Here, the investigators aimed to conduct a randomized study on evaluating the antiviral efficacy, safety, and tolerability of switching from adefovir to tenofovir in chronic hepatitis B patients who have suboptimal response to adefovir-based combination rescue therapy due to nucleoside analogues Resistance (SATIS study).
Detailed description
The major goal of antiviral therapy against chronic hepatitis B is to suppress viral replications successfully, ultimately preventing the chronic liver damage, development of liver cirrhosis and hepatocellular carcinoma. In Korea, the number of multi-drug resistant CHB has been rapidly increased last few years. It is because that the national health insurance coverage is very limited for the patients who experienced primary treatment failure. The only switch to adefovir has been allowed in lamivudine resistant patients and thus this sequential rescue therapy generated multi-drug resistance to both adefovir and another drugs. Thus, nowadays, add-on therapy rather than switch therapy might be preferred from major guidelines in this point.
However, the number of suboptimal responders to rescue combination therapy is also increasing. As a matter of fact, according to the investigations in Korea, HBV DNA undetectability at 48 weeks of adefovir and lamivudine combination rescue therapy for patients with lamivudine resistance was reported to be only 32.4%, which suggested that the appropriate another rescue therapy might be urgently required. However, there is no promising oral antiviral agents to control these patients in Asia-Pacific region, where tenofovir is not widely available. Tenofovir has a higher potent antiviral efficacy and a negligible drug resistance rate. It belongs to the different class compared to other oral nucleoside analogues (NAs) such as lamivudine, telbivudine, clevudine and entecavir. The switch from adefovir to tenofovir in patients who have insufficient hepatitis B virus (HBV) suppression (HBV DNA ≥ 60 IU/mL by PCR) may lead to increased viral suppression or more HBeAg loss/seroconversion. The results of this study will provide a rationale for switch from adefovir to tenofovir in combination to another drug continued (lamivudine, telbivudine, clevudine and entecavir).
Here, the investigators aimed to conduct a randomized study on evaluating the antiviral efficacy, safety, and tolerability of switching from adefovir to tenofovir in chronic hepatitis B patients who have suboptimal response to adefovir-based combination rescue therapy due to nucleoside analogues Resistance (SATIS study).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Adefovir, nucleoside analogues | Active comparator | Drug: Switching from adefovir (10mg/day) to tenofovir (300mg/day)Nucleoside analogues (Lamivudine 100mg, Telbivudine 600mg, Entecavir 1mg, or Clevudine 30mg) + Adefovir 10mg |
| Tenofovir, nucleoside analogues | Experimental | Drug: Switching from adefovir (10mg/day) to tenofovir (300mg/day)Nucleoside analogues (Lamivudine 100mg, Telbivudine 600mg, Entecavir 1mg, or Clevudine 30mg) + Tenofovir 300mg |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- subjects with age >= 20 years
- subjects with chronic hepatitis B
- subjects treated with nucleoside analogues plus adefovir for at least 6 months due to resistance to nucleoside analogues (Lamivudine, Telbivudine, Entecavir, or Clevudine)
- subjects with partial virologic response to nucleoside analogues plus adefovir HBV DNA ≥ 60 IU/mL)
- subjects with ALT less than 5 times of upper limit of normal
Key exclusion criteria (10 listed)
- subjects with decompensate liver cirrhosis Child-Pugh B, C)
- subjects with Adefovir mutation
- subjects with HCV, HDV, or HIV infection
- pregnant or lactating women
- women of childbearing age who do not use the appropriate contraception method
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 |
|---|---|---|
| Switching from adefovir (10mg/day) to tenofovir (300mg/day)active comparator: Nucleoside analogues (Lamivudine 100mg, Telbivudine 600mg, Entecavir 1mg, or Clevudine 30mg/day) + Adefovir 10mg/day Experimental: Nucleoside analogues (Lamivudine 100mg, Telbivudine 600mg, Entecavir 1mg, or Clevudine 30mg/day) + Tenofovir 300mg/day | Drug | Adefovir, nucleoside analogues, Tenofovir, nucleoside analogues |
Primary outcome
number of patients with complete virologic response (HBV DNA < 60 IU/mL, approximately 300 copies/mL) at 48 weeks treatment
Time frame: 48 weeks
Complete virologic response (HBV DNA < 60 IU/mL, approximately 300 copies/mL) at 48 weeks treatment
5 secondary outcomes
number of patients with antiviral response at 48 weeks therapy
Time frame: 48 weeks
number of patients with biochemical response at 48 weeks therapy
Time frame: 48 weeks
number of patients with serologic response at 48 weeks therapy
Time frame: 48 weeks
number of patients with appearance of resistant mutant strain at 48 weeks
Time frame: 48 weeks
Number of Participants with Adverse Events
Time frame: 48 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 May 2012.
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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
Department of Internal Medicine, Yonsei University College of Medicine
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 Switching from adefovir (10mg/day) to tenofovir (300mg/day) in people with Chronic Hepatitis B, run by Yonsei University 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 6 inclusion and 10 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 10 May 2012. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact BeomKyung Kim, Dr. (82-2-2228-1930, beomkkim@yuhs.ac), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
number of patients with complete virologic response (HBV DNA < 60 IU/mL, approximately 300 copies/mL) at 48 weeks treatment (time frame: 48 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 May 2012.