Hepatitis B, ChronicPhase 3NCT02327416
A Prospective Clinical Trial in Chronic Hepatitis B Patients NAs (Nucleotides or Nucleosides) Experienced (Anchor Study)
A Phase 3 study testing Y peginterferon alfa-2b, Granulocyte-macrophage colony stimulating factor and Entecavir and or adefovir dipivoxil in people with Hepatitis B, Chronic, run by Tongji Hospital at 4 sites in China.
Trial summary
This study is a multi-center, randomized, prospective, open-label Phase III Clinical trial to assess the efficacy and safety of combination and sequential treatment with Y peginterferon Alfa-2b,entecavir and GMCSF in chronic hepatitis B patients nucleotides or nucleosides experienced. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Hepatitis B, Chronic
- What is being tested?
- Y peginterferon alfa-2b, Granulocyte-macrophage colony stimulating factor and Entecavir and or adefovir dipivoxil
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 300 participants
- Where
- 4 sitesChina
- Study dates
- Oct 2014to Jun 2019
- Phase
- Phase 3
- 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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male and female patients from 18 to 65 years of age;
- HBsAg positive, entecavir and or adefovir dipivoxil are used at least 1 year including patients with nucleotides or nucleoside resistance history if their HBV DNA obtained control;
- Before nucleotides or nucleosides treatment, ALT > 2 ULN, HBV DNA >10000 copies/ml,HBsAg positive;
- Serum HBV DNA < 1000 copies/ml;
- Serum HBsAg < 3000 IU/ml;
- HBsAg positive;
Show all 9Show fewer
- Negative urine or serum pregnancy test (for women of childbearing potential) documented within the 24-hour period prior to the first dose of test drug;
- Absence of cirrhosis confirmed by ultrasonic test;
- Agree to participate in the study and sign the patient informed consent.
Who cannot join
- Patients who had NAs resistance and HBV DNA > 1000 copies/ml, or treatment of drugs with IFN longer than 6 months;
- Other antiviral, anti-neoplastic or immunomodulatory treatment (including supra physiologic doses of steroids and radiation) 6 months prior to the first dose of randomized treatment (except for 7 days of acyclovir for herpetic lesions more than 1 month prior to first administration of randomized treatment). Patients who are expected to need systemic antiviral therapy other than that provided by the study at any time during their participation are also excluded;
- Women with ongoing pregnancy or breast-feeding;
- Co-infection with active hepatitis A, hepatitis C, hepatitis D(Those hospitals which have the ability to do the test will do) and/or human immunodeficiency virus (HIV);
- ALT >10 ULN;
- Evidence of decompensated liver disease (Child-Pugh score > 5 ). Child-Pugh > 5 means, if one of the following 5 conditions are met, the patient has to be excluded:
Show all 25Show fewer
- one of the following 5 conditions are met, the patient has to be excluded:
- Serum albumin < 3.5 g/L;
- Prothrombin time > 3 seconds prolonged;
- Serum bilirubin > 34 µ mol/L;
- History of encephalopathy;
- History of variceal bleeding;
- Ascites;
- History or other evidence of a medical condition associated with chronic liver disease other than viral hepatitis (e.g., hemochromatosis, autoimmune hepatitis, metabolic liver disease, alcoholic liver disease, toxin exposures, thalassemia);
- Signs or symptoms of hepatocellular carcinoma, patients with a value of alpha-fetoprotein > 100 ng/mL are excluded, unless stability (less than 10% increase) has been documented over at least the previous 3 months. Patients with values < 20 ng/mL but > 100 ng/mL may be enrolled, if hepatic neoplasia has been excluded by liver imaging;
- Neutrophil count < 1500 cells/mm3 or platelet count <90,000 cells/mm3 at screening;
- Hemoglobin < 11.5 g/dL for females and <12.5 g/dL for men;
- Serum creatinine level > 1.5 ULN in screening period.
- Phosphorus < 0.65 mmol/L;
- ANA > 1:100;
- History of severe psychiatric disease, especially depression. Severe psychiatric disease is defined as treatment with an antidepressant medication or a major tranquilizer at therapeutic doses for major depression or psychosis, respectively, for at least 3 months at any previous time or any history of the following: a suicidal attempt hospitalization for psychiatric disease, or a period of disability due to a psychiatric disease;
- History of a severe seizure disorder or current anticonvulsant use;
- History of immunologically mediated disease, (e.g., inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, scleroderma, rheumatoid arthritis etc.);
- History of chronic pulmonary disease associated with functional limitation;
- Diseases that IFN and Nucleotides or nucleosides are not suitable.
Trial locations and contacts
4 sites in 1 country.
China4 sites, 4 recruiting
- Recruiting
Beijing Youan Hospital
Beijing, Beijing Municipality, 100069
Xinyue Chen, Doctor, 86 13911212398, chenxydoc@163.com
Yali Liu, Doctor, 86 13260255331, xxbi@163.com
- Recruiting
Xiangya Hospital, Central South University
Changsha, Hunan, 410008
Deming Tan, Doctor, 86 13975886582, dmt3008@163.com
Lei Fu, Doctor, 86 15084739488, 936512615@qq.com
- Recruiting
The First Affiliated Hospital of Wenzhou Medical University
Wenzhou, Zhejiang, 325000
Yongping Chen, Doctor, 86 13505777281, 13505777281@163.com
Lanman Xu, Doctor, 86 13587646315, 13587646315@163.com
- Recruiting
Tongji Hospital
Wuhan, Hubei, 430030
Qin Ning, Doctor, 86 27 83662391, qning@vip.sina.com
Meifang Han, Doctor, 86 27 83662391, hanmeifang@hotmail.com
About this study
Official title: A Prospective Randomized Clinical Trial of Combination Sequential Treatment With Y Peginterferon Alfa-2b and ETV (Entecavir) in CHB (Chronic Hepatitis B) Patients NAs (Nucleotides or Nucleosides) Experienced (Anchor Study)
This study is a multi-center, randomized, prospective, open-label Phase III Clinical trial to assess the efficacy and safety of combination and sequential treatment with Y peginterferon Alfa-2b,entecavir and GMCSF in chronic hepatitis B patients nucleotides or nucleosides experienced. Patients were randomized to one of 3 groups to receive different antiviral treatment.
Read the detailed description
Patients who have been pretreated with and responded to one or two nucleotides or nucleosides for at least one year, with HBV (Hepatitis B Virus) DNA less than 1000 copies/ml and HBsAg less 3000 IU/ml were randomized to one of 3 groups, to receive Y peginterferon Alfa-2b 180mcg/week for 96 weeks, entecavir 0.5 mg po daily for 48 weeks plus GMCSF (Granulocyte-macrophage colony stimulating factor) for 48 weeks, or Y peginterferon Alfa-2b 180mcg/week for 96 weeks and entecavir 0.5 mg po daily for 48 weeks, or only ETV for 96 weeks.
- Conditions
- Hepatitis B, Chronic
- Being tested
- Y peginterferon alfa-2b, Granulocyte-macrophage colony stimulating factor, Entecavir and or adefovir dipivoxil
- 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.
Y peginterferon alfa-2bDrug
Also called peginterferon alfa-2b
In arm 2 and 3, Y peginterferon alfa-2b is used for 96 weeks
Granulocyte-macrophage colony stimulating factorDrug
Also called GMCSF
In arm 3, Granulocyte-macrophage colony stimulating factor is used for 48 weeks intermittently
Entecavir and or adefovir dipivoxilDrug
Also called ETV and or ADV
In arm 1, Entecavir and or adefovir dipivoxil are used for 96 weeks and the follow up 24 weeks as conventional control, In arm 2 and 3, Entecavir and or adefovir dipivoxil are used for 48 weeks.
| Study group | Role | What they receive |
|---|---|---|
| 1,conventional control group | Active comparator | Drug: Entecavir and or adefovir dipivoxil are used for 96 weeks and the follow up 24 weeks. Entecavir 0.5mg po daily or plus ADV （adefovir dipivoxil）10mg po daily. Receives: Drug: Entecavir and or adefovir dipivoxil |
| 2，combination and sequential group | Experimental | Drug: Y peginterferon Alfa-2b 180 micrograms sc/week for 96 weeks; Drug: Entecavir and or adefovir dipivoxil are used for 48 weeks. Entecavir 0.5mg po daily for 48 weeks or plus ADV 10mg po daily. Receives: Drug: Y peginterferon alfa-2b; Drug: Entecavir and or adefovir dipivoxil |
| 3, multitarget group | Experimental | Drug: Y peginterferon Alfa-2b 180 micrograms sc/week for 96 weeks; Drug: Granulocyte-macrophage colony stimulating factor is used for 48 weeks; Drug: Entecavir and or adefovir dipivoxil are used for 48 weeks. Entecavir 0.5mg po daily for 48 weeks or plus ADV 10mg po daily. Receives: Drug: Y peginterferon alfa-2b; Drug: Granulocyte-macrophage colony stimulating factor; Drug: Entecavir and or adefovir dipivoxil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of HBsAg loss at week 96
Change from baseline in Percentage of HBsAg loss at week 96
Measured: week 96
Secondary outcomes (2)
Change from baseline in HBsAg quantification and HBsAg decline at week 96
HBsAg quantification and HBsAg decline from baseline are measured.
Measured: week 96
Change from baseline in HBsAg seroconversion at week 96
HBsAg seroconversion from baseline is measured.
Measured: week 96
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Dec 2014 (estimated)
- Study startOct 2014
- Primary completionDec 2018 (estimated)
- Study completionJun 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)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 Tongji 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tongji Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Xiamen Amoytop Biotech Co., Ltd.
- Responsible party
- Principal investigator, Qin Ning, Tongji Hospital
- Investigators
- Qin Ning, Doctor, Principal investigator, Department of Infectious Diseases, Tongji Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02327416
- Sponsor's protocol ID
- Anchor study
- Status last verified
- Aug 2016
- First submitted
- 23 Nov 2014
- Last updated
- 15 Aug 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Wu D, Huang D, Peng S, Chen Y, Yang F, Zhang X, Fu L, Xu L, Jiang J, Zheng Q, Chen X, Liu Y, Dou X, Ma K, Xi D, Wang P, Sun L, He R, Tian Y, Yin P, Yan W, Han M, Ning Q. Efficacy and safety of entecavir, peginterferon alfa-2b and GM-CSF combination therapy: the anchor randomized controlled trial. Hepatol Int. 2026 Feb;20(1):31-45. doi: 10.1007/s12072-025-10977-2. Epub 2025 Dec 9.
PubMed 41366186Gu M, Wu W, You J, Wu Q, Huang F, Zhang Y, Wang P, Xi D, Yan W, Wang X, Chen T, Wu D, Ning Q, Han M. High-Throughput Viral Integration Detection Reveals Baseline Breakpoints Burden Associated With HBsAg Seroclearance. Aliment Pharmacol Ther. 2025 Nov;62(9):887-900. doi: 10.1111/apt.70270. Epub 2025 Jul 16.
PubMed 40665748Huang D, Wu D, Wang P, Wang Y, Yuan W, Hu D, Hu J, Wang Y, Tao R, Xiao F, Zhang X, Wang X, Han M, Luo X, Yan W, Ning Q. End-of-treatment HBcrAg and HBsAb levels identify durable functional cure after Peg-IFN-based therapy in patients with CHB. J Hepatol. 2022 Jul;77(1):42-54. doi: 10.1016/j.jhep.2022.01.021. Epub 2022 Feb 8.
PubMed 35149125
Study at a glance
From the registry record, last updated by the sponsor on 15 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective Randomized Clinical Trial of Combination Sequential Treatment With Y Peginterferon Alfa-2b and ETV (Entecavir) in CHB (Chronic Hepatitis B) Patients NAs (Nucleotides or Nucleosides) Experienced (Anchor Study)
- ClinicalTrials.gov ID
- NCT02327416
- Acronym / sponsor ID
- Anchor study
- Conditions
- Hepatitis B, Chronic
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- Tongji HospitalUniversity, hospital or other
- Collaborators
- Xiamen Amoytop Biotech Co., Ltd.
- Study start
- Oct 2014
- Primary completion
- Dec 2018 (estimated)
- Study completion
- Jun 2019 (estimated)
- First posted
- 30 Dec 2014 (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.
This study is a multi-center, randomized, prospective, open-label Phase III Clinical trial to assess the efficacy and safety of combination and sequential treatment with Y peginterferon Alfa-2b,entecavir and GMCSF in chronic hepatitis B patients nucleotides or nucleosides experienced. Patients were randomized to one of 3 groups to receive different antiviral treatment.
Detailed description
Patients who have been pretreated with and responded to one or two nucleotides or nucleosides for at least one year, with HBV (Hepatitis B Virus) DNA less than 1000 copies/ml and HBsAg less 3000 IU/ml were randomized to one of 3 groups, to receive Y peginterferon Alfa-2b 180mcg/week for 96 weeks, entecavir 0.5 mg po daily for 48 weeks plus GMCSF (Granulocyte-macrophage colony stimulating factor) for 48 weeks, or Y peginterferon Alfa-2b 180mcg/week for 96 weeks and entecavir 0.5 mg po daily for 48 weeks, or only ETV for 96 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1,conventional control group | Active comparator | Drug: Entecavir and or adefovir dipivoxilDrug: Entecavir and or adefovir dipivoxil are used for 96 weeks and the follow up 24 weeks. Entecavir 0.5mg po daily or plus ADV （adefovir dipivoxil）10mg po daily. |
| 2，combination and sequential group | Experimental | Drug: Y peginterferon alfa-2b, Drug: Entecavir and or adefovir dipivoxilDrug: Y peginterferon Alfa-2b 180 micrograms sc/week for 96 weeks; Drug: Entecavir and or adefovir dipivoxil are used for 48 weeks. Entecavir 0.5mg po daily for 48 weeks or plus ADV 10mg po daily. |
| 3, multitarget group | Experimental | Drug: Y peginterferon alfa-2b, Drug: Granulocyte-macrophage colony stimulating factor, Drug: Entecavir and or adefovir dipivoxilDrug: Y peginterferon Alfa-2b 180 micrograms sc/week for 96 weeks; Drug: Granulocyte-macrophage colony stimulating factor is used for 48 weeks; Drug: Entecavir and or adefovir dipivoxil are used for 48 weeks. Entecavir 0.5mg po daily for 48 weeks or plus ADV 10mg po daily. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Male and female patients from 18 to 65 years of age;
- HBsAg positive, entecavir and or adefovir dipivoxil are used at least 1 year including patients with nucleotides or nucleoside resistance history if their HBV DNA obtained control;
- Before nucleotides or nucleosides treatment, ALT > 2 ULN, HBV DNA >10000 copies/ml,HBsAg positive;
- Serum HBV DNA < 1000 copies/ml;
- Serum HBsAg < 3000 IU/ml;
Key exclusion criteria (25 listed)
- Patients who had NAs resistance and HBV DNA > 1000 copies/ml, or treatment of drugs with IFN longer than 6 months;
- Other antiviral, anti-neoplastic or immunomodulatory treatment (including supra physiologic doses of steroids and radiation) 6 months prior to the first dose of randomized treatment (except for 7 days of acyclovir for herpetic lesions more than 1 month prior to first administration of randomized treatment). Patients who are expected to need systemic antiviral therapy other than that provided by the study at any time during their participation are also excluded;
- Women with ongoing pregnancy or breast-feeding;
- Co-infection with active hepatitis A, hepatitis C, hepatitis D(Those hospitals which have the ability to do the test will do) and/or human immunodeficiency virus (HIV);
- ALT >10 ULN;
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 |
|---|---|---|
| Y peginterferon alfa-2bAlso: peginterferon alfa-2bIn arm 2 and 3, Y peginterferon alfa-2b is used for 96 weeks | Drug | 2，combination and sequential group, 3, multitarget group |
| Granulocyte-macrophage colony stimulating factorAlso: GMCSFIn arm 3, Granulocyte-macrophage colony stimulating factor is used for 48 weeks intermittently | Drug | 3, multitarget group |
| Entecavir and or adefovir dipivoxilAlso: ETV and or ADVIn arm 1, Entecavir and or adefovir dipivoxil are used for 96 weeks and the follow up 24 weeks as conventional control, In arm 2 and 3, Entecavir and or adefovir dipivoxil are used for 48 weeks. | Drug | 1,conventional control group, 2，combination and sequential group, 3, multitarget group |
Primary outcome
Percentage of HBsAg loss at week 96
Time frame: week 96
Change from baseline in Percentage of HBsAg loss at week 96
2 secondary outcomes
Change from baseline in HBsAg quantification and HBsAg decline at week 96
Time frame: week 96
Change from baseline in HBsAg seroconversion at week 96
Time frame: week 96
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Aug 2016.
- Derived from this study: PubMed 41366186Wu D, Huang D, Peng S, Chen Y, Yang F, Zhang X, Fu L, Xu L, Jiang J, Zheng Q, Chen X, Liu Y, Dou X, Ma K, Xi D, Wang P, Sun L, He R, Tian Y, Yin P, Yan W, Han M, Ning Q. Efficacy and safety of entecavir, peginterferon alfa-2b and GM-CSF combination therapy: the anchor randomized controlled trial. Hepatol Int. 2026 Feb;20(1):31-45. doi: 10.1007/s12072-025-10977-2. Epub 2025 Dec 9.
- Derived from this study: PubMed 40665748Gu M, Wu W, You J, Wu Q, Huang F, Zhang Y, Wang P, Xi D, Yan W, Wang X, Chen T, Wu D, Ning Q, Han M. High-Throughput Viral Integration Detection Reveals Baseline Breakpoints Burden Associated With HBsAg Seroclearance. Aliment Pharmacol Ther. 2025 Nov;62(9):887-900. doi: 10.1111/apt.70270. Epub 2025 Jul 16.
- Derived from this study: PubMed 35149125Huang D, Wu D, Wang P, Wang Y, Yuan W, Hu D, Hu J, Wang Y, Tao R, Xiao F, Zhang X, Wang X, Han M, Luo X, Yan W, Ning Q. End-of-treatment HBcrAg and HBsAb levels identify durable functional cure after Peg-IFN-based therapy in patients with CHB. J Hepatol. 2022 Jul;77(1):42-54. doi: 10.1016/j.jhep.2022.01.021. Epub 2022 Feb 8.
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.
Qin Ning, Doctor principal investigator
Department of Infectious Diseases, Tongji Hospital
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Y peginterferon alfa-2b, Granulocyte-macrophage colony stimulating factor and Entecavir and or adefovir dipivoxil in people with Hepatitis B, Chronic, run by Tongji Hospital at 4 sites 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 9 inclusion and 25 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 15 Aug 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 Qin Ning (86 27 83662391, qning@vip.sina.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of HBsAg loss at week 96 (time frame: week 96). 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 NCT02327416, which also lists 3 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 15 Aug 2016.