Hepatitis B, ChronicPhase 4NCT00917761
Entecavir and Pegasys Sequential Therapy Versus Pegasys for HBeAg Negative Chronic Hepatitis B
A Phase 4 study testing Entecavir and peginterferon (Pegasys) (52 weeks), Peginterferon (Pegasys) (96 weeks) and Peginterferon (Pegasys) (48 weeks) in people with Hepatitis B, Chronic, run by National Taiwan University Hospital at 6 sites in Taiwan.
Trial summary
Currently, peginterferon alfa-2a or oral nucleos(t)ides are approved for the treatment with HBeAg negative CHB, with the overall ALT normalization and HBV viral suppression far from satisfactory. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatitis B, Chronic
- What is being tested?
- Entecavir and peginterferon (Pegasys) (52 weeks), Peginterferon (Pegasys) (96 weeks) and Peginterferon (Pegasys) (48 weeks)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 300 participants
- Where
- 6 sitesTaiwan
- Study dates
- Feb 2007to Dec 2013
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Chronic hepatitis B (presence of HBsAg > 6 months) with anti-HBe persistence and abscence of HBeAg for more than 3 months
- Age older than 18 years
- HBV DNA > 2,000 IU/mL for more than 2 occasions
- Serum ALT levels between 2 to 10 folds the upper limit of normal (ULN)
- A liver biopsy compatible with chronic hepatitis B
Who cannot join
- Anemia (hemoglobin < 13 gram per deciliter for men and < 12 gram per deciliter for women)
- Neutropenia (neutrophil count <1,500 per cubic milliliter)
- Thrombocytopenia (platelet <90,000 per cubic milliliter)
- Co-infection with hepatitis B virus (HBV), hepatitis D virus (HDV) or human immunodeficiency virus (HIV)
- Chronic alcohol abuse (daily consumption > 20 gram per day)
- Decompensated liver disease (Child-Pugh class B or C)
Show all 16Show fewer
- Serum creatinine level more than 1.5 times the upper limit of normal
- Autoimmune liver disease
- Neoplastic disease
- An organ transplant
- Immunosuppressive therapy
- Poorly controlled autoimmune diseases, pulmonary diseases, cardiac diseases, psychiatric diseases, neurological diseases, diabetes mellitus
- Evidence of drug abuse
- Unwilling to have contraception
- Known allergic reaction to entecavir or peginterferon alfa-2a
- Unwilling to sign inform consent
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
Taiwan6 sites, 6 recruiting
- Recruiting
National Taiwan University Hosptial, Yun-Lin Branch
Douliu
Shih-Jer Hsu, MD
Shih-Jer Hsu, MD
- Recruiting
Taichung Veterans General Hospital
Taichung
Sheng-Shun Yang, MD, PhD
Sheng-Shun Yang, MD, PhD
- Recruiting
National Taiwan University Hospital
Taipei, 10002
Chen-Hua Liu, MD
Chen-Hua Liu, MD
- Recruiting
Buddhist Tzu Chi General Hospital
Taipei
Ching-Sheng Hsu, MD
Ching-Sheng Hsu, MD
- Recruiting
Far Eastern Memorial Hospital
Taipei
Cheng-Chao Liang, MD
Cheng-Chao Liang, MD
- Recruiting
Ren-Ai Branch, Taipei Municipal Hospital
Taipei
Chih-Lin Lin, MD
Chih-Lin Lin, MD
About this study
Official title: Entecavir and Peginterferon Alfa-2a Sequential Therapy Versus Peginterferon Alfa-2a Monotherapy for HBeAg Negative Chronic Hepatitis B
Currently, peginterferon alfa-2a or oral nucleos(t)ides are approved for the treatment with HBeAg negative CHB, with the overall ALT normalization and HBV viral suppression far from satisfactory. Therefore, efforts on the various combinations with the currently available drugs are needed to improve the overall response rates. The simultaneous combination therapy with oral nucleoside and peginterferon alfa-2a from large-scaled randomized trials did not show a superior response rate over peginterferon alfa-2a monotherapy. Recently, sequential monotherapy with lamivudine for the first 4 weeks, followed by weekly peginterferon alfa-2a has shown favorable HBeAg seroconversion rate over peginterferon alfa-2a monotherapy, based on the assumption that early viral suppression by lamivudine can restore the immune function to facilitate the later immunomodulatory response by peginterferon alfa-2a. Furthermore, prior studies using 24 months of standard interferon alfa showed better ALT normalization and HBV suppression rates to 12 months of therapy. With the recent introduction of entecavir, the more potent oral nucleoside with few drug resistance, sequential monotherapy with entecavir can potently suppress HBV DNA with 4 weeks of treatment, which may facilitate the response of peginterferon alfa-2a to achieve HBV viral suppression. Therefore, we aimed to conduct a placebo controlled randomized control trial to evaluate if adding entecavir early in the course of therapy or extending the treatment duration of peginterferon alfa-2a can improve the treatment response.
Read the detailed description
Chronic hepatitis B (CHB) is prevalent in the world, with estimated chronic carriers of 350 millions worldwide. Currently, peginterferon alfa-2a or oral nucleos(t)ides are approved for the treatment with HBeAg negative CHB, with the overall ALT normalization and HBV viral suppression far from satisfactory. Therefore, efforts on the various combinations with the currently available drugs are needed to improve the overall response rates. The simultaneous combination therapy with oral nucleoside and peginterferon alfa-2a from large-scaled randomized trials did not show a superior response rate over peginterferon alfa-2a monotherapy. Recently, sequential monotherapy with lamivudine for the first 4 weeks, followed by weekly peginterferon alfa-2a has shown favorable HBeAg seroconversion rate over peginterferon alfa-2a monotherapy, based on the assumption that early viral suppression by lamivudine can restore the immune function to facilitate the later immunomodulatory response by peginterferon alfa-2a. Furthermore, prior studies using 24 months of standard interferon alfa showed better ALT normalization and HBV suppression rates to 12 months of therapy. With the recent introduction of entecavir, the more potent oral nucleoside with few drug resistance, sequential monotherapy with entecavir can potently suppress HBV DNA with 4 weeks of treatment, which may facilitate the response of peginterferon alfa-2a to achieve HBV viral suppression. Therefore, we aimed to conduct a placebo controlled randomized control trial to evaluate if adding entecavir early in the course of therapy or extending the treatment duration of peginterferon alfa-2a can improve the treatment response.
- Conditions
- Hepatitis B, Chronic
- Being tested
- Entecavir and peginterferon (Pegasys) (52 weeks), Peginterferon (Pegasys) (96 weeks), Peginterferon (Pegasys) (48 weeks)
- Keywords
- Hepatitis B, chronic, Peginterferon alfa-2a, 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.
Entecavir and peginterferon (Pegasys) (52 weeks)Drug
Also called Entecavir (Baraclude)0.5 mg/day po at week 1-4, Peginterferon alfa-2a (Pegasys) 180 ug/week sc at week 5-52
Entecavir 0.5 mg/day po at week 1-4 Peginterferon alfa-2a 180 ug/week sc at week 5-52
Peginterferon (Pegasys) (96 weeks)Drug
Also called Peginterferon alfa-2a (Pegasys) 180 ug/week sc at week 1-96
Peginterferon alfa-2a 180 ug/week sc at week 1-96
Peginterferon (Pegasys) (48 weeks)Drug
Also called Peginterferon alfa-2a (Pegasys) 180 ug/week sc at week 1-48
Peginterferon alfa-2a 180 ug/week sc at week 1-48
| Study group | Role | What they receive |
|---|---|---|
| Entecavir and peginterferon (52 weeks) | Experimental | Entecavir 0.5 mg/day po at week 1-4 Peginterferon alfa-2a 180 ug/week sc at week 5-52 Receives: Drug: Entecavir and peginterferon (Pegasys) (52 weeks) |
| Peginterferon (96 weeks) | Experimental | Peginterferon alfa-2a 180 ug/week sc at week 1-96 Receives: Drug: Peginterferon (Pegasys) (96 weeks) |
| Peginterferon (48 weeks) | Active comparator | Peginterferon alfa-2a 180 ug/week sc at week 1-48 Receives: Drug: Peginterferon (Pegasys) (48 weeks) |
What is being measured
The primary outcome is the main question the study is designed to answer.
HBV virologic response (HBV DNA < 2,000 IU/mL) 6 months after the cessation of treatment
Measured: 2.5 years
Secondary outcomes (1)
ALT normalization rate (ALT < 40 IU/L) 6 months after the cessation of treatment
Measured: 2.5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jun 2009 (estimated)
- Study startFeb 2007
- Primary completionDec 2013 (estimated)
- Study completionDec 2013 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatitis B, ChronicStudies of the same condition, open and under way.
- More trials run by National Taiwan University HospitalThe 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
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Taiwan University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Science and Technology Council, Taiwan
- Responsible party
- Sponsor
- Investigators
- Chen-Hua Liu, MD, Study chair, National Taiwan University HospitalJia-Horng Kao, MD, PhD, Principal investigator, National Taiwan University HospitalShih-Jer Hsu, MD, Principal investigator, National Taiwan University Hosptial, Yun-Lin BranchChih-Lin Lin, MD, Principal investigator, Ren-Ai Branch, Taipei City HospitalCheng-Chao Liang, MD, Principal investigator, Far Eastern Memorial HospitalChing-Sheng Hsu, MD, Principal investigator, Buddhist Tzu Chi General HospitalSheng-Shun Yang, MD, PhD, Principal investigator, Taichung Veterans General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00917761
- Sponsor's protocol ID
- 950924
- Status last verified
- Dec 2012
- First submitted
- 8 Jun 2009
- Last updated
- 20 Dec 2012
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 20 Dec 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Entecavir and Peginterferon Alfa-2a Sequential Therapy Versus Peginterferon Alfa-2a Monotherapy for HBeAg Negative Chronic Hepatitis B
- ClinicalTrials.gov ID
- NCT00917761
- Acronym / sponsor ID
- 950924
- Conditions
- Hepatitis B, Chronic
- Keywords
- Hepatitis B, chronic, Peginterferon alfa-2a, Entecavir
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- National Taiwan University HospitalUniversity, hospital or other
- Collaborators
- National Science and Technology Council, Taiwan
- Study start
- Feb 2007
- Primary completion
- Dec 2013 (estimated)
- Study completion
- Dec 2013 (estimated)
- First posted
- 10 Jun 2009 (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.
Currently, peginterferon alfa-2a or oral nucleos(t)ides are approved for the treatment with HBeAg negative CHB, with the overall ALT normalization and HBV viral suppression far from satisfactory. Therefore, efforts on the various combinations with the currently available drugs are needed to improve the overall response rates. The simultaneous combination therapy with oral nucleoside and peginterferon alfa-2a from large-scaled randomized trials did not show a superior response rate over peginterferon alfa-2a monotherapy. Recently, sequential monotherapy with lamivudine for the first 4 weeks, followed by weekly peginterferon alfa-2a has shown favorable HBeAg seroconversion rate over peginterferon alfa-2a monotherapy, based on the assumption that early viral suppression by lamivudine can restore the immune function to facilitate the later immunomodulatory response by peginterferon alfa-2a. Furthermore, prior studies using 24 months of standard interferon alfa showed better ALT normalization and HBV suppression rates to 12 months of therapy. With the recent introduction of entecavir, the more potent oral nucleoside with few drug resistance, sequential monotherapy with entecavir can potently suppress HBV DNA with 4 weeks of treatment, which may facilitate the response of peginterferon alfa-2a to achieve HBV viral suppression. Therefore, we aimed to conduct a placebo controlled randomized control trial to evaluate if adding entecavir early in the course of therapy or extending the treatment duration of peginterferon alfa-2a can improve the treatment response.
Detailed description
Chronic hepatitis B (CHB) is prevalent in the world, with estimated chronic carriers of 350 millions worldwide. Currently, peginterferon alfa-2a or oral nucleos(t)ides are approved for the treatment with HBeAg negative CHB, with the overall ALT normalization and HBV viral suppression far from satisfactory. Therefore, efforts on the various combinations with the currently available drugs are needed to improve the overall response rates. The simultaneous combination therapy with oral nucleoside and peginterferon alfa-2a from large-scaled randomized trials did not show a superior response rate over peginterferon alfa-2a monotherapy. Recently, sequential monotherapy with lamivudine for the first 4 weeks, followed by weekly peginterferon alfa-2a has shown favorable HBeAg seroconversion rate over peginterferon alfa-2a monotherapy, based on the assumption that early viral suppression by lamivudine can restore the immune function to facilitate the later immunomodulatory response by peginterferon alfa-2a. Furthermore, prior studies using 24 months of standard interferon alfa showed better ALT normalization and HBV suppression rates to 12 months of therapy. With the recent introduction of entecavir, the more potent oral nucleoside with few drug resistance, sequential monotherapy with entecavir can potently suppress HBV DNA with 4 weeks of treatment, which may facilitate the response of peginterferon alfa-2a to achieve HBV viral suppression. Therefore, we aimed to conduct a placebo controlled randomized control trial to evaluate if adding entecavir early in the course of therapy or extending the treatment duration of peginterferon alfa-2a can improve the treatment response.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Entecavir and peginterferon (52 weeks) | Experimental | Drug: Entecavir and peginterferon (Pegasys) (52 weeks)Entecavir 0.5 mg/day po at week 1-4 Peginterferon alfa-2a 180 ug/week sc at week 5-52 |
| Peginterferon (96 weeks) | Experimental | Drug: Peginterferon (Pegasys) (96 weeks)Peginterferon alfa-2a 180 ug/week sc at week 1-96 |
| Peginterferon (48 weeks) | Active comparator | Drug: Peginterferon (Pegasys) (48 weeks)Peginterferon alfa-2a 180 ug/week sc at week 1-48 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Chronic hepatitis B (presence of HBsAg > 6 months) with anti-HBe persistence and abscence of HBeAg for more than 3 months
- Age older than 18 years
- HBV DNA > 2,000 IU/mL for more than 2 occasions
- Serum ALT levels between 2 to 10 folds the upper limit of normal (ULN)
- A liver biopsy compatible with chronic hepatitis B
Key exclusion criteria (16 listed)
- Anemia (hemoglobin < 13 gram per deciliter for men and < 12 gram per deciliter for women)
- Neutropenia (neutrophil count <1,500 per cubic milliliter)
- Thrombocytopenia (platelet <90,000 per cubic milliliter)
- Co-infection with hepatitis B virus (HBV), hepatitis D virus (HDV) or human immunodeficiency virus (HIV)
- Chronic alcohol abuse (daily consumption > 20 gram per day)
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 |
|---|---|---|
| Entecavir and peginterferon (Pegasys) (52 weeks)Also: Entecavir (Baraclude)0.5 mg/day po at week 1-4, Peginterferon alfa-2a (Pegasys) 180 ug/week sc at week 5-52Entecavir 0.5 mg/day po at week 1-4 Peginterferon alfa-2a 180 ug/week sc at week 5-52 | Drug | Entecavir and peginterferon (52 weeks) |
| Peginterferon (Pegasys) (96 weeks)Also: Peginterferon alfa-2a (Pegasys) 180 ug/week sc at week 1-96Peginterferon alfa-2a 180 ug/week sc at week 1-96 | Drug | Peginterferon (96 weeks) |
| Peginterferon (Pegasys) (48 weeks)Also: Peginterferon alfa-2a (Pegasys) 180 ug/week sc at week 1-48Peginterferon alfa-2a 180 ug/week sc at week 1-48 | Drug | Peginterferon (48 weeks) |
Primary outcome
HBV virologic response (HBV DNA < 2,000 IU/mL) 6 months after the cessation of treatment
Time frame: 2.5 years
1 secondary outcome
ALT normalization rate (ALT < 40 IU/L) 6 months after the cessation of treatment
Time frame: 2.5 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Dec 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.
Chen-Hua Liu, MD study chair
National Taiwan University Hospital
Jia-Horng Kao, MD, PhD principal investigator
National Taiwan University Hospital
Shih-Jer Hsu, MD principal investigator
National Taiwan University Hosptial, Yun-Lin Branch
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Entecavir and peginterferon (Pegasys) (52 weeks), Peginterferon (Pegasys) (96 weeks) and Peginterferon (Pegasys) (48 weeks) in people with Hepatitis B, Chronic, run by National Taiwan University Hospital at 6 sites in Taiwan.
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 5 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: status not confirmed, as of the sponsor's last update on 20 Dec 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Taiwan. 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 Chen-Hua Liu, MD (886-2-23123456 ext. 63572, jacque_liu@mail2000.com.tw), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
HBV virologic response (HBV DNA < 2,000 IU/mL) 6 months after the cessation of treatment (time frame: 2.5 years). 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 20 Dec 2012.