NCT03357822

Brief Summary

The aim of the prospective real-world study is to evaluate whether sequential combination therapy with pegylated interferon plus entecavir/tenofovir could induce higher rates of HBsAg loss in nucleoside-treated patients with chronic hepatitis B compared to continuous nucleoside 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
2,000

participants targeted

Target at P75+ for phase_4

Timeline
Completed

Started Jan 2018

Longer than P75 for phase_4

Geographic Reach
1 country

12 active sites

Status
unknown

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

Trial Relationships

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 20, 2017

Completed
10 days until next milestone

First Posted

Study publicly available on registry

November 30, 2017

Completed
2 months until next milestone

Study Start

First participant enrolled

January 25, 2018

Completed
4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 25, 2022

Completed
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

July 25, 2022

Completed
Last Updated

April 25, 2018

Status Verified

April 1, 2018

Enrollment Period

4 years

First QC Date

November 20, 2017

Last Update Submit

April 23, 2018

Conditions

Keywords

Chronic hepatitis BNucleoside analogPegylated InterferonSequential combination therapyHBsAg loss

Outcome Measures

Primary Outcomes (1)

  • HBsAg loss rate

    Percentages of patients who achieve HBsAg loss at week 48

    at week 48

Secondary Outcomes (25)

  • HBsAg loss rate

    at week 72

  • HBsAg loss rate

    at week 96

  • HBsAg level

    at week 48

  • HBsAg level

    at week 72

  • HBsAg level

    at week 96

  • +20 more secondary outcomes

Study Arms (2)

Sequential combination therapy group

EXPERIMENTAL

Patients are treated with pegylated Interferon (180ug, subcutaneously, once a week) plus entecavir (0.5mg, orally, every day) or tenofovir disoproxil fumarate (300mg, orally, every day) for 48/72/96 weeks

Drug: Pegylated interferonDrug: EntecavirDrug: Tenofovir disoproxil fumarate

Nucleoside therapy group

ACTIVE COMPARATOR

Patients are treated with entecavir (0.5mg, orally, every day) or tenofovir disoproxil fumarate (300mg, orally, every day) for 96 weeks

Drug: EntecavirDrug: Tenofovir disoproxil fumarate

Interventions

180ug Pegylated interferon is injected subcutaneously once a week

Also known as: Pegylated interferon (PegIFN)
Sequential combination therapy group

0.5mg entecavir is orally taken every day

Also known as: Entecavir (ETV)
Nucleoside therapy groupSequential combination therapy group

300mg tenofovir is orally taken every day

Also known as: Tenofovir disoproxil fumarate (TDF)
Nucleoside therapy groupSequential combination therapy 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;
  • Before nucleotides or nucleosides treatment, ALT \> 2 upper limit of normal value (ULN), HBV DNA \>10000 copies/ml, HBsAg positive;
  • Serum HBV DNA ≤ 500 copies/ml;
  • 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:

  • HBV DNA \> 500 copies/ml;
  • 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 (12)

302 Military Hospital of China

Beijing, Beijing Municipality, China

RECRUITING

BeiJing YouAn Hospital, Capital Medical University

Beijing, Beijing Municipality, China

NOT YET RECRUITING

The First Hospital Affiliated to AMU

Chongqing, Chongqing Municipality, China

NOT YET RECRUITING

The First Affiliated Hospital of Fujian Medical University

Fuzhou, Fujian, China

NOT YET RECRUITING

The First Affiliated Hospital of Guangxi Medical University

Nanning, Guangxi, China

NOT YET RECRUITING

The First Affiliated Hospital of College of Medicine, Zhejiang University

Zhejiang, Hangzhou, Doctor, China

NOT YET RECRUITING

Departmen of infectious disease, Xiangya Hospital, Central-south Universit

Changsha, Hunan, China

NOT YET RECRUITING

The Second Xiangya Hospital of Central South University

Changsha, Hunan, China

NOT YET RECRUITING

The First Affiliated Hospital with Nanjing Medical University

Nanjing, Jiangsu, China

NOT YET RECRUITING

The Second Hospital of Nanjing

Nanjing, Jiangsu, China

NOT YET RECRUITING

Traditional Chinese Medicine,Xiamen Hospital

Shantou, Xiamen, China

NOT YET RECRUITING

The first affiliated hospital of Wenzhou medical universtiy

Wenzhou, Zhejiang, China

NOT YET RECRUITING

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

entecavirTenofovir

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)

OrganophosphonatesOrganophosphorus CompoundsOrganic ChemicalsAdeninePurinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic Compounds

Study Officials

  • Qin Ning

    Department of Infectious Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Study Design

Study Type
interventional
Phase
phase 4
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Prof

Study Record Dates

First Submitted

November 20, 2017

First Posted

November 30, 2017

Study Start

January 25, 2018

Primary Completion

January 25, 2022

Study Completion

July 25, 2022

Last Updated

April 25, 2018

Record last verified: 2018-04

Locations