Chronic Hepatitis BPhase 4STEEPNCT01711567
Tenofovir Disoproxil Fumarate vs. Entecavir in Chronic Hepatitis B Patients With Partial Virologic Response to Entecavir
A Phase 4 study testing tenofovir and entecavir in people with Chronic Hepatitis B, run by Korea University at 1 site in South Korea.
Trial summary
Entecavir, a potent antiviral agent, has been widely used for treatment-naïve chronic hepatitis B patients. However, about 20% of patients showed partial virologic response after 2 year of entecavir therapy (33% in HBeAg positive, 10% in HBeAg negative patients). Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Chronic Hepatitis B
- What is being tested?
- tenofovir and entecavir
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteSouth Korea
- Study dates
- Apr 2013to Nov 2016
- 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 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- CHB patients (positive HBsAg more than 6 months)
- Age 19 years old
- HBeAg positive or negative patients
- Patients receiving entecavir 0.5 mg more than 12 months
- Detectable HBV DNA by real time PCR (HBV > 60 IU/mL)
- Compensated liver function (Child-Pugh-Turcotte score ≤7, prothrombin time 3 sec above ULN or INR ≤1.5, serum albumin >3 g/dL, total bilirubin <2.5 mg/dL, no history of variceal bleeding, diuretics or ascites requiring paracentesis, hepatic encephalopathy)
Who cannot join
- History of treatment with nucleotide analogue other than 0.5 mg of ETV
- Serum creatinine level > 1.5 mg/dL or creatinine clearance < 50 mL/min
- Absolute neutrophil count ≤ 1000 cell/mL
- Hemoglobin level ≤ 10 g/dL in men or ≤ 9 g/dL in women
- Antiviral resistance mutations on rtT184, rtS202, or rtM250 + rtM204V/I
- A positive antibody test for human immunodeficiency virus, hepatitis C virus, or hepatitis D virus
Show all 9Show fewer
- Pregnancy or lactation
- HCC (in cases where alfa-fetoprotein levels were over 100 ng/mL, abdominal computed tomography or magnetic resonance image was performed to exclude HCC)
- Untreated malignancy other than HCC.
Trial locations and contacts
1 site in 1 country.
South Korea1 site
Korea University Ansan Hospital
Ansan, Gyeonggi-do, 425-707
About this study
Official title: Switching to Tenofovir Disoproxil Fumarate vs. Continuing Entecavir in Chronic Hepatitis B Patients With Partial Virologic Response During Entecavir Therapy: STEEP Study
Entecavir, a potent antiviral agent, has been widely used for treatment-naïve chronic hepatitis B patients. However, about 20% of patients showed partial virologic response after 2 year of entecavir therapy (33% in HBeAg positive, 10% in HBeAg negative patients). Tenofovir is a nucleotide analogue with more potent antiviral activity. In addition, there is no cross resistance between the two drugs. Therefore it is assumed that tenofovir would be effective in the treatment of chronic hepatitis B patients who shows partial virologic response (detectable HBV DNA by real time PCR after 12 months of treatment) despite treatment with entecavir. In this study, we will compare the efficacy of switching to tenofovir with continuing entecavir in patients who shows partial virologic response to entecavir.
Read the detailed description
The number of patients needed was calculated using PASS 2008. We hypothesized that two-thirds (65%) of the patients receiving TDF, and one-fifth (20%) of the patients receiving ETV, would achieve virologic response. We also assumed a 15% drop-out rate; thus, 22 patients were needed in each group to achieve 80% power to demonstrate a difference between the groups with a 5% level of significance.
The primary efficacy end point will be analyzed on a per-protocol basis, including only those patients who had completed the treatment schedule of study. In contrast, the intention-to-treat analysis will include all randomized subjects, even those dropped-out from the study before 12 months, as cases of treatment failure.
- Conditions
- Chronic Hepatitis B
- Being tested
- tenofovir, entecavir
- Keywords
- Chronic Hepatitis B, TENOFOVIR, ENTECAVIR, PARTIAL RESPONDER
- 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.
tenofovirDrug
Also called tenofovir (viread)
tenofovir 300 mg qd
entecavirDrug
Also called entecavir(baraclude) 0.5 mg qd
entecavir 0.5 mg qd
| Study group | Role | What they receive |
|---|---|---|
| entecavir | Active comparator | standard drugs Receives: Drug: entecavir |
| tenofovir | Active comparator | study drugs Receives: Drug: tenofovir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Virologic response rate at year 1 (12 months) (HBV DNA < 20 IU/mL)
Measured: up to the end of year 1 (12 months)
Secondary outcomes (1)
-Degree of HBV DNA reduction, mean HBV DNA, biochemical and serologic response rates, resistance, and adverse events at year 1
Measured: up to the end of year 1 (12 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2012 (estimated)
- Study startApr 2013
- Primary completionDec 2015
- Study completionNov 2016
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.
- 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
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Korea University
- Sponsor type
- University, hospital or other
- Collaborators
- Gilead Sciences
- Responsible party
- Principal investigator, Hyung Joon Yim, Korea University
- Investigators
- Hyung Joon Yim, M.D., Principal investigator, Korea University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01711567
- Sponsor's protocol ID
- STEEP study
- Acronym
- STEEP
- Status last verified
- Nov 2016
- First submitted
- 17 Oct 2012
- Last updated
- 9 Nov 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 9 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Switching to Tenofovir Disoproxil Fumarate vs. Continuing Entecavir in Chronic Hepatitis B Patients With Partial Virologic Response During Entecavir Therapy: STEEP Study
- ClinicalTrials.gov ID
- NCT01711567
- Acronym / sponsor ID
- STEEP / STEEP study
- Conditions
- Chronic Hepatitis B
- Keywords
- Chronic Hepatitis B, TENOFOVIR, ENTECAVIR, PARTIAL RESPONDER
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Korea UniversityUniversity, hospital or other
- Collaborators
- Gilead Sciences
- Study start
- Apr 2013
- Primary completion
- Dec 2015 (actual)
- Study completion
- Nov 2016 (actual)
- First posted
- 22 Oct 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.
Entecavir, a potent antiviral agent, has been widely used for treatment-naïve chronic hepatitis B patients. However, about 20% of patients showed partial virologic response after 2 year of entecavir therapy (33% in HBeAg positive, 10% in HBeAg negative patients). Tenofovir is a nucleotide analogue with more potent antiviral activity. In addition, there is no cross resistance between the two drugs. Therefore it is assumed that tenofovir would be effective in the treatment of chronic hepatitis B patients who shows partial virologic response (detectable HBV DNA by real time PCR after 12 months of treatment) despite treatment with entecavir. In this study, we will compare the efficacy of switching to tenofovir with continuing entecavir in patients who shows partial virologic response to entecavir.
Detailed description
The number of patients needed was calculated using PASS 2008. We hypothesized that two-thirds (65%) of the patients receiving TDF, and one-fifth (20%) of the patients receiving ETV, would achieve virologic response. We also assumed a 15% drop-out rate; thus, 22 patients were needed in each group to achieve 80% power to demonstrate a difference between the groups with a 5% level of significance.
The primary efficacy end point will be analyzed on a per-protocol basis, including only those patients who had completed the treatment schedule of study. In contrast, the intention-to-treat analysis will include all randomized subjects, even those dropped-out from the study before 12 months, as cases of treatment failure.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| entecavir | Active comparator | Drug: entecavirstandard drugs |
| tenofovir | Active comparator | Drug: tenofovirstudy drugs |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- CHB patients (positive HBsAg more than 6 months)
- Age 19 years old
- HBeAg positive or negative patients
- Patients receiving entecavir 0.5 mg more than 12 months
- Detectable HBV DNA by real time PCR (HBV > 60 IU/mL)
Key exclusion criteria (9 listed)
- History of treatment with nucleotide analogue other than 0.5 mg of ETV
- Serum creatinine level > 1.5 mg/dL or creatinine clearance < 50 mL/min
- Absolute neutrophil count ≤ 1000 cell/mL
- Hemoglobin level ≤ 10 g/dL in men or ≤ 9 g/dL in women
- Antiviral resistance mutations on rtT184, rtS202, or rtM250 + rtM204V/I
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 |
|---|---|---|
| tenofovirAlso: tenofovir (viread)tenofovir 300 mg qd | Drug | tenofovir |
| entecavirAlso: entecavir(baraclude) 0.5 mg qdentecavir 0.5 mg qd | Drug | entecavir |
Primary outcome
Virologic response rate at year 1 (12 months) (HBV DNA < 20 IU/mL)
Time frame: up to the end of year 1 (12 months)
1 secondary outcome
-Degree of HBV DNA reduction, mean HBV DNA, biochemical and serologic response rates, resistance, and adverse events at year 1
Time frame: up to the end of year 1 (12 months)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Nov 2016.
Related trials for Chronic Hepatitis B
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.
Hyung Joon Yim, M.D. principal investigator
Korea University
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 tenofovir and entecavir in people with Chronic Hepatitis B, run by Korea 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 9 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 9 Nov 2016. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Virologic response rate at year 1 (12 months) (HBV DNA < 20 IU/mL) (time frame: up to the end of year 1 (12 months)). 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 9 Nov 2016.