Chronic Hepatitis BPhase 4NCT01906580
Combination or Sequential Therapy of Peginterferon Alfa-2a and Entecavir for Patients With Chronic Hepatitis B
A Phase 4 study testing Peg-IFNα-2a and Entecavir in people with Chronic Hepatitis B, run by Beijing 302 Hospital at 1 site in China.
Trial summary
Currently, seven medications are approved for the treatment of hepatitis B: two formulations of interferon and five nucleons(t)ide analogues. The current treatment strategy of chronic hepatitis B is now standard: initial selection of entecavir, tenofovir, or peginterferon alfa-2a (peg-IFNα-2a). Read more about this study
- Who is it for?
- Ages 16 to 60 years
- Conditions the study is for
- Chronic Hepatitis B
- What is being tested?
- Peg-IFNα-2a and Entecavir
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 105 participants
- Where
- 1 siteChina
- Study dates
- Jul 2011to Jul 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 16 to 60 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Age≥16 years
- HBsAg positive for more than 6 months, and HBeAg detection is positive for two times in 6 months before enrollment
- Serum HBVDNA >2×10^4IU/ml
- 80U/L < serum ALT < 400U/L, and TBIL < 34 umol/L
- Serum ALT < 80U/L, but hepatic inflammation scores ≥ G2 or hepatic fibrosis stage ≥ S3
Who cannot join
- Co-infected with HCV, HDV or HIV, or autoimmune liver diseases combined
- Hepatic decompensation
- received antiviral therapy or immunosuppressant drugs before 6 months prior to enrollment
- Blood routine examination: WBC <3×10^9/L，neutrophile granulocyte < 1.5×10^9/L，PLT <80×10^9/L
- Renal function: creatinine >1.5 times of upper normal limit
- Alcoholism or a history of addiction and abuse
- Combined with hepatocarcinoma
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Research Center for Biological Therapy, The Institute of Translational Hepatology, Beijing 302 Hospital
Beijing, 100039
Sa Lv, MD, 86-10-63879735 ext. 2015.12, lvsa@sina.com
About this study
Official title: Combination or Sequential Therapy of Peginterferon Alfa-2a and Entecavir for Hepatitis B e Antigen-positive Patients With Chronic Hepatitis B
Currently, seven medications are approved for the treatment of hepatitis B: two formulations of interferon and five nucleons(t)ide analogues. The current treatment strategy of chronic hepatitis B is now standard: initial selection of entecavir, tenofovir, or peginterferon alfa-2a (peg-IFNα-2a). Interferon is administered for a finite duration while nucleotide analogues are usually administered for many years. But among hepatitis B e antigen （HBeAg） positive patients with high serum hepatitis B virus DNA levels, the rates of virological response are poor. And antiviral drug resistance is a major limiting factor to the success of nucleotide analogue treatment. Therefore, combination therapy using peginterferon with an oral agent with a high genetic barrier to resistance might be superior to standard current monotherapy. However, the addition of lamivudine to peg-IFNα-2a therapy led to a greater decrease in serum HBV DNA levels during treatment but did not increase the rate of HBeAg sero¬conversion. Entecavir is a nucleoside analogue superior to lamivudine and adefovir in achieving higher virological response, histological improvement and normalisation of ALT. Moreover, Entecavir has a high genetic barrier with a very low incidence of drug resistance. This study is aimed to investigate the efficacy of combination or sequential therapy using peg-IFNα-2a and entecavir in HBeAg-positive chronic hepatitis B(CHB) patients.
- Conditions
- Chronic Hepatitis B
- Being tested
- Peg-IFNα-2a, Entecavir
- Keywords
- HBV, entecavir, peginterferon
- 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.
Peg-IFNα-2aDrug
Also called peginterferon alfa-2a
180ug peg-IFNα-2a, subcutaneous injection per week
EntecavirDrug
Also called Baraclude
0.5mg,oral administration every day
| Study group | Role | What they receive |
|---|---|---|
| Peg-IFNα-2a monotherapy | Experimental | Participants will receive 180ug peg-IFNα-2a therapy for 72 weeks, and then followed to 96 weeks. Receives: Drug: Peg-IFNα-2a |
| Sequential therapy | Experimental | Participants will receive entecavir monotherapy for 12 weeks, and 180ug peg-IFNα-2a therapy is added for the following 12 weeks. After that, entecavir will be stopped and 180ug peg-IFNα-2a monotherapy for the following 48 weeks. All participants will followed to 96 weeks. Receives: Drug: Peg-IFNα-2a; Drug: Entecavir |
| Combination therapy | Experimental | Participants will receive 180ug peg-IFNα-2a combined with entecavir therapy for 72 weeks, and then followed to 96 weeks. Receives: Drug: Peg-IFNα-2a; Drug: Entecavir |
What is being measured
The primary outcome is the main question the study is designed to answer.
the rates of HBeAg seroconversion
Measured: at week 72
Secondary outcomes (5)
normalisation of ALT
Measured: at week 2、4、12、24、36、48、60、72、84、96
liver histological improvement
Measured: at baseline and at week 72
The rates of HBsAg negative
Measured: at week12、24、36、48、60、72、84、96
the rate of virological response
Measured: at week 4、12、24、36、48、60、72、84、96
the rate of HBeAg negative
Measured: at week 12、24、36、48、60、72、84、96
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jul 2013 (estimated)
- Study startJul 2011
- Primary completionJul 2016 (estimated)
- Study completionJul 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- 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
- 105 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Beijing 302 Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Fu-Sheng Wang, Professor, Principal investigator, Beijing 302 Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01906580
- Sponsor's protocol ID
- 2011030D
- Status last verified
- Aug 2015
- First submitted
- 30 May 2013
- Last updated
- 17 Aug 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Kwon H, Lok AS. Hepatitis B therapy. Nat Rev Gastroenterol Hepatol. 2011 May;8(5):275-84. doi: 10.1038/nrgastro.2011.33. Epub 2011 Mar 22.
PubMed 21423260Ayoub WS, Keeffe EB. Review article: current antiviral therapy of chronic hepatitis B. Aliment Pharmacol Ther. 2011 Nov;34(10):1145-58. doi: 10.1111/j.1365-2036.2011.04869.x. Epub 2011 Oct 7.
PubMed 21978243Kuo A, Gish R. Chronic hepatitis B infection. Clin Liver Dis. 2012 May;16(2):347-69. doi: 10.1016/j.cld.2012.03.003.
PubMed 22541703Rehermann B, Nascimbeni M. Immunology of hepatitis B virus and hepatitis C virus infection. Nat Rev Immunol. 2005 Mar;5(3):215-29. doi: 10.1038/nri1573.
PubMed 15738952
Study at a glance
From the registry record, last updated by the sponsor on 17 Aug 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combination or Sequential Therapy of Peginterferon Alfa-2a and Entecavir for Hepatitis B e Antigen-positive Patients With Chronic Hepatitis B
- ClinicalTrials.gov ID
- NCT01906580
- Acronym / sponsor ID
- 2011030D
- Conditions
- Chronic Hepatitis B
- Keywords
- HBV, entecavir, peginterferon
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 105 participants (estimated)
- Lead sponsor
- Beijing 302 HospitalUniversity, hospital or other
- Study start
- Jul 2011
- Primary completion
- Jul 2016 (estimated)
- Study completion
- Jul 2016 (estimated)
- First posted
- 24 Jul 2013 (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, seven medications are approved for the treatment of hepatitis B: two formulations of interferon and five nucleons(t)ide analogues. The current treatment strategy of chronic hepatitis B is now standard: initial selection of entecavir, tenofovir, or peginterferon alfa-2a (peg-IFNα-2a). Interferon is administered for a finite duration while nucleotide analogues are usually administered for many years. But among hepatitis B e antigen （HBeAg） positive patients with high serum hepatitis B virus DNA levels, the rates of virological response are poor. And antiviral drug resistance is a major limiting factor to the success of nucleotide analogue treatment. Therefore, combination therapy using peginterferon with an oral agent with a high genetic barrier to resistance might be superior to standard current monotherapy. However, the addition of lamivudine to peg-IFNα-2a therapy led to a greater decrease in serum HBV DNA levels during treatment but did not increase the rate of HBeAg sero¬conversion. Entecavir is a nucleoside analogue superior to lamivudine and adefovir in achieving higher virological response, histological improvement and normalisation of ALT. Moreover, Entecavir has a high genetic barrier with a very low incidence of drug resistance. This study is aimed to investigate the efficacy of combination or sequential therapy using peg-IFNα-2a and entecavir in HBeAg-positive chronic hepatitis B(CHB) patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Peg-IFNα-2a monotherapy | Experimental | Drug: Peg-IFNα-2aParticipants will receive 180ug peg-IFNα-2a therapy for 72 weeks, and then followed to 96 weeks. |
| Sequential therapy | Experimental | Drug: Peg-IFNα-2a, Drug: EntecavirParticipants will receive entecavir monotherapy for 12 weeks, and 180ug peg-IFNα-2a therapy is added for the following 12 weeks. After that, entecavir will be stopped and 180ug peg-IFNα-2a monotherapy for the following 48 weeks. All participants will followed to 96 weeks. |
| Combination therapy | Experimental | Drug: Peg-IFNα-2a, Drug: EntecavirParticipants will receive 180ug peg-IFNα-2a combined with entecavir therapy for 72 weeks, and then followed to 96 weeks. |
Who may qualify
- Ages
- 16 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- Age≥16 years
- HBsAg positive for more than 6 months, and HBeAg detection is positive for two times in 6 months before enrollment
- Serum HBVDNA >2×10^4IU/ml
- 80U/L < serum ALT < 400U/L, and TBIL < 34 umol/L
- Serum ALT < 80U/L, but hepatic inflammation scores ≥ G2 or hepatic fibrosis stage ≥ S3
Key exclusion criteria (7 listed)
- Co-infected with HCV, HDV or HIV, or autoimmune liver diseases combined
- Hepatic decompensation
- received antiviral therapy or immunosuppressant drugs before 6 months prior to enrollment
- Blood routine examination: WBC <3×10^9/L，neutrophile granulocyte < 1.5×10^9/L，PLT <80×10^9/L
- Renal function: creatinine >1.5 times of upper normal limit
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 |
|---|---|---|
| Peg-IFNα-2aAlso: peginterferon alfa-2a180ug peg-IFNα-2a, subcutaneous injection per week | Drug | Combination therapy, Peg-IFNα-2a monotherapy, Sequential therapy |
| EntecavirAlso: Baraclude0.5mg,oral administration every day | Drug | Combination therapy, Sequential therapy |
Primary outcome
the rates of HBeAg seroconversion
Time frame: at week 72
5 secondary outcomes
normalisation of ALT
Time frame: at week 2、4、12、24、36、48、60、72、84、96
liver histological improvement
Time frame: at baseline and at week 72
The rates of HBsAg negative
Time frame: at week12、24、36、48、60、72、84、96
the rate of virological response
Time frame: at week 4、12、24、36、48、60、72、84、96
the rate of HBeAg negative
Time frame: at week 12、24、36、48、60、72、84、96
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Aug 2015.
- Background: PubMed 21423260Kwon H, Lok AS. Hepatitis B therapy. Nat Rev Gastroenterol Hepatol. 2011 May;8(5):275-84. doi: 10.1038/nrgastro.2011.33. Epub 2011 Mar 22.
- Background: PubMed 21978243Ayoub WS, Keeffe EB. Review article: current antiviral therapy of chronic hepatitis B. Aliment Pharmacol Ther. 2011 Nov;34(10):1145-58. doi: 10.1111/j.1365-2036.2011.04869.x. Epub 2011 Oct 7.
- Background: PubMed 22541703Kuo A, Gish R. Chronic hepatitis B infection. Clin Liver Dis. 2012 May;16(2):347-69. doi: 10.1016/j.cld.2012.03.003.
- Background: PubMed 15738952Rehermann B, Nascimbeni M. Immunology of hepatitis B virus and hepatitis C virus infection. Nat Rev Immunol. 2005 Mar;5(3):215-29. doi: 10.1038/nri1573.
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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.
Fu-Sheng Wang, Professor principal investigator
Beijing 302 Hospital
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 Peg-IFNα-2a and Entecavir in people with Chronic Hepatitis B, run by Beijing 302 Hospital at 1 site in China.
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 7 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 17 Aug 2015. 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 China. 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 Sa Lv, MD (86-10-63879735 ext. 2014.12, lvsa@sina.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
the rates of HBeAg seroconversion (time frame: at week 72). 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 NCT01906580, which also lists 4 linked publications.
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 17 Aug 2015.