NCT02327416

Brief 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. Patients were randomized to one of 3 groups to receive different antiviral treatment.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
300

participants targeted

Target at P50-P75 for phase_3

Timeline
Completed

Started Oct 2014

Longer than P75 for phase_3

Geographic Reach
1 country

4 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

October 1, 2014

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

November 23, 2014

Completed
1 month until next milestone

First Posted

Study publicly available on registry

December 30, 2014

Completed
3.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2018

Completed
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2019

Completed
Last Updated

August 15, 2016

Status Verified

August 1, 2016

Enrollment Period

4.2 years

First QC Date

November 23, 2014

Last Update Submit

August 11, 2016

Conditions

Hepatitis B, Chronic

Outcome Measures

Primary Outcomes (1)

  • Percentage of HBsAg loss at week 96

    Change from baseline in Percentage of HBsAg loss at week 96

    week 96

Secondary Outcomes (2)

  • Change from baseline in HBsAg quantification and HBsAg decline at week 96

    week 96

  • Change from baseline in HBsAg seroconversion at week 96

    week 96

Other Outcomes (3)

  • Percentage of HBeAg loss or HBeAg seroconversion at week 96 for HBeAg positive patients

    week 96

  • Percentage of HBV DNA normalization and ALT normalization at week 96

    week 96

  • Percentage of sustained virology response at week 120

    week 120

Study Arms (3)

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.

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.

Drug: Y peginterferon alfa-2bDrug: 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.

Drug: Y peginterferon alfa-2bDrug: Granulocyte-macrophage colony stimulating factorDrug: Entecavir and or adefovir dipivoxil

Interventions

Y peginterferon alfa-2bDRUG

In arm 2 and 3, Y peginterferon alfa-2b is used for 96 weeks

Also known as: peginterferon alfa-2b
2，combination and sequential group3, multitarget group
Granulocyte-macrophage colony stimulating factorDRUG

In arm 3, Granulocyte-macrophage colony stimulating factor is used for 48 weeks intermittently

Also known as: GMCSF
3, multitarget group
Entecavir and or adefovir dipivoxilDRUG

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.

Also known as: ETV and or ADV
1,conventional control group2，combination and sequential group3, multitarget group

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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;
  • 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.

You may not qualify if:

  • 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:
  • 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;
  • +10 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

Beijing Youan Hospital

Beijing, Beijing Municipality, 100069, China

RECRUITING

Tongji Hospital

Wuhan, Hubei, 430030, China

RECRUITING

Xiangya Hospital, Central South University

Changsha, Hunan, 410008, China

RECRUITING

The First Affiliated Hospital of Wenzhou Medical University

Wenzhou, Zhejiang, 325000, China

RECRUITING

Related Publications (3)

  • 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. 2025 Dec 9. doi: 10.1007/s12072-025-10977-2. Online ahead of print.

    PMID: 41366186DERIVED

  • Gu 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.

    PMID: 40665748DERIVED

  • Huang 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.

    PMID: 35149125DERIVED

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

peginterferon alfa-2bColony-Stimulating Factorsentecaviradefovir dipivoxil

Condition Hierarchy (Ancestors)

Hepatitis BBlood-Borne InfectionsCommunicable DiseasesInfectionsHepadnaviridae InfectionsDNA Virus InfectionsVirus DiseasesHepatitis, Viral, HumanHepatitis, ChronicHepatitisLiver DiseasesDigestive System DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

GlycoproteinsGlycoconjugatesCarbohydratesHematopoietic Cell Growth FactorsCytokinesIntercellular Signaling Peptides and ProteinsPeptidesAmino Acids, Peptides, and ProteinsProteinsBiological Factors

Study Officials

  • Qin Ning, Doctor

    Department of Infectious Diseases, Tongji Hospital

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Qin Ning

CONTACT

86 27 83662391qning@vip.sina.com

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Director and Chair of Department of Infectious Diseases

Study Record Dates

First Submitted

November 23, 2014

First Posted

December 30, 2014

Study Start

October 1, 2014

Primary Completion

December 1, 2018

Study Completion

June 1, 2019

Last Updated

August 15, 2016

Record last verified: 2016-08

Locations

CN(4)