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Optimized Treatment of Peginterferon Alfa 2a in Treatment Experienced Patients With HBV Related Liver Fibrosis

Primary Purpose

Hepatitis B, Liver Fibrosis

Status
Unknown status
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
Tenofovir Disoproxil Fumarate
PEG-Interferon alfa 2a
Sponsored by
Third Affiliated Hospital, Sun Yat-Sen University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatitis B focused on measuring hepatitis b virus, liver fibrosis, peg interferon alfa-2a, tenofovir disoproxil fumarate

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Positive hepatitis b surface antigen or hepatitis b virus DNA > 0.5 year;
  2. Receiving treatment of nucleoside/nucleotide analogues at least one year before recruited;
  3. Age from 18 to 55 years old;
  4. Normal liver function(ALT<ULN,AST<ULN and TBil<ULN).
  5. Undetectable hepatitis b virus DNA or less than 100IU/ml.
  6. LSM between 6 and 12 kpa measured by fibroscan;
  7. Liver ultrasound: normal or echo thickening, and portal vein diameter ≤ 12mm.

Exclusion Criteria:

  1. Decompensated cirrhosis, hepatocellular carcinoma or other malignancy;
  2. Pregnancy, lactation or female has plan of pregnancy within 18 months;
  3. Accompanied with other active liver diseases(HAV, HCV, HDV, HEV, autoimmune liver disease, drug-induced liver injury, alcoholic liver disease, genetic metabolic liver disease, etc.)；
  4. Accompanied with human immunodeficiency virus infection or congenital immune deficiency diseases;
  5. Accompanied with severe diabetes, autoimmune diseases etc. and other important organ dysfunctions;
  6. Patients who fail to comply with this research arrangement and sign an informed consent form
  7. Patients can not follow-up;
  8. Investigator considering inappropriate.

Sites / Locations

  • Third Affiliated Hospital of Sun Yat-sen UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

TDF group

Combination group

Arm Description

93 patients would receive treatment of oral medication of tenofovir disoproxil fumarate (TDF) 300mg once per day from baseline to 48 weeks. Then they would receive oral medication of TDF 300 mg once per day from 49 to 96 weeks.

93 patients would receive treatment of subcutaneous injection of peginterferon alfa 2a 180 μg once per week and meanwhile oral medication of tenofovir disoproxil fumarate (TDF) 300 mg once per day from baseline to 48 weeks. Then they would receive oral medication of TDF 300 mg once per day from 49 to 96 weeks.

Outcomes

Primary Outcome Measures

Ratio of regression of fibrosis
Regression of fibrosis was defined as liver stiffness measured by transient elastography changed from 9~12kpa to 6~9kpa or below, and from 6~9kpa to less than 6kpa. After treatment, the proportion of patients with regression of fibrosis in the two groups was the ratio of regression of fibrosis, separately.

Secondary Outcome Measures

Ratio of loss of hepatitis b e antigen or/and seroconversion
Hepatitis b e antigen and hepatitis b e antibody would be tested to know the ratio of patients with negative hepatitis B e antigen and positive hepatitis B e antibody at 4 time points after anti-virus treatment.
Ratio of loss of hepatitis b s antigen or/and seroconversion
Hepatitis b s antigen and hepatitis b s antibody would be tested to know the ratio of patients with negative hepatitis B s antigen and positive hepatitis B s antibody at 4 time points after anti-virus treatment.
Logarithmic mean of HBsAg decline
Hepatitis b s antigen would be tested to know the decline of patients with positive hepatitis B s antigen at 4 time points after anti-virus treatment.

Full Information

First Posted
May 19, 2019
Last Updated
January 17, 2020
Sponsor
Third Affiliated Hospital, Sun Yat-Sen University
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1. Study Identification

Unique Protocol Identification Number
NCT03957629
Brief Title
Optimized Treatment of Peginterferon Alfa 2a in Treatment Experienced Patients With HBV Related Liver Fibrosis
Official Title
An Open, Multi-center Clinical Study of Combination Therapy With Tenofovir Disoproxil Fumarate and Peginterferon Alpha 2a in Nucleos(t)Ide Analogs Experienced Patients With HBV Related Hepatic Fibrosis.
Study Type
Interventional

2. Study Status

Record Verification Date
January 2020
Overall Recruitment Status
Unknown status
Study Start Date
November 6, 2019 (Actual)
Primary Completion Date
July 30, 2021 (Anticipated)
Study Completion Date
July 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Third Affiliated Hospital, Sun Yat-Sen University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Compared to TDF, peginterferon alfa 2a may has more therapeutic efficacy in hepatitis B surface antigen or e antigen seroconversion and anti-tumor occurrence in chronic hepatitis b patients. We design this study to compare the effectiveness and safety between the combination therapy of TDF and peg-IFN with TDF alone in NAs experienced patients with HBV related liver fibrosis. Especially the improvement of liver fibrosis and the occurrence of long-term end-stage liver disease such as cirrhosis, liver cancer, etc.
Detailed Description
Compared to TDF, peginterferon alfa 2a may has more therapeutic efficacy in hepatitis B surface antigen or e antigen seroconversion and anti-tumor occurrence in chronic hepatitis b patients. We design this study to compare the effectiveness and safety between the combination therapy of TDF and peg-IFN with TDF alone in NAs experienced patients with HBV related liver fibrosis. Especially the improvement of liver fibrosis and the occurrence of long-term end-stage liver disease such as cirrhosis, liver cancer, etc. Main purpose: Comparing the improvement rate of liver fibrosis. Secondary purpose: Comparing the incidence of adverse events. Comparing the incidence of cirrhosis, hepatocellular carcinoma, and liver failure. Comparing the rates of HBsAg and HBeAg serological conversion.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis B, Liver Fibrosis
Keywords
hepatitis b virus, liver fibrosis, peg interferon alfa-2a, tenofovir disoproxil fumarate

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
186 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
TDF group
Arm Type
Active Comparator
Arm Description
93 patients would receive treatment of oral medication of tenofovir disoproxil fumarate (TDF) 300mg once per day from baseline to 48 weeks. Then they would receive oral medication of TDF 300 mg once per day from 49 to 96 weeks.
Arm Title
Combination group
Arm Type
Active Comparator
Arm Description
93 patients would receive treatment of subcutaneous injection of peginterferon alfa 2a 180 μg once per week and meanwhile oral medication of tenofovir disoproxil fumarate (TDF) 300 mg once per day from baseline to 48 weeks. Then they would receive oral medication of TDF 300 mg once per day from 49 to 96 weeks.
Intervention Type
Drug
Intervention Name(s)
Tenofovir Disoproxil Fumarate
Other Intervention Name(s)
Viread, Beixin
Intervention Description
Oral medication of Tenofovir Disoproxil Fumarate 300mg once per day.
Intervention Type
Drug
Intervention Name(s)
PEG-Interferon alfa 2a
Other Intervention Name(s)
Pegasys
Intervention Description
Subcutaneous injection of Peginterferon Alfa-2a 180 μg once per week.
Primary Outcome Measure Information:
Title
Ratio of regression of fibrosis
Description
Regression of fibrosis was defined as liver stiffness measured by transient elastography changed from 9~12kpa to 6~9kpa or below, and from 6~9kpa to less than 6kpa. After treatment, the proportion of patients with regression of fibrosis in the two groups was the ratio of regression of fibrosis, separately.
Time Frame
48 weeks; 96 weeks
Secondary Outcome Measure Information:
Title
Ratio of loss of hepatitis b e antigen or/and seroconversion
Description
Hepatitis b e antigen and hepatitis b e antibody would be tested to know the ratio of patients with negative hepatitis B e antigen and positive hepatitis B e antibody at 4 time points after anti-virus treatment.
Time Frame
24 week, 48 week, 72 week, 96 week
Title
Ratio of loss of hepatitis b s antigen or/and seroconversion
Description
Hepatitis b s antigen and hepatitis b s antibody would be tested to know the ratio of patients with negative hepatitis B s antigen and positive hepatitis B s antibody at 4 time points after anti-virus treatment.
Time Frame
24 week, 48 week, 72 week, 96 week
Title
Logarithmic mean of HBsAg decline
Description
Hepatitis b s antigen would be tested to know the decline of patients with positive hepatitis B s antigen at 4 time points after anti-virus treatment.
Time Frame
24 week, 48 week, 72 week, 96 week

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Positive hepatitis b surface antigen or hepatitis b virus DNA > 0.5 year; Receiving treatment of nucleoside/nucleotide analogues at least one year before recruited; Age from 18 to 55 years old; Normal liver function(ALT<ULN,AST<ULN and TBil<ULN). Undetectable hepatitis b virus DNA or less than 100IU/ml. LSM between 6 and 12 kpa measured by fibroscan; Liver ultrasound: normal or echo thickening, and portal vein diameter ≤ 12mm. Exclusion Criteria: Decompensated cirrhosis, hepatocellular carcinoma or other malignancy; Pregnancy, lactation or female has plan of pregnancy within 18 months; Accompanied with other active liver diseases(HAV, HCV, HDV, HEV, autoimmune liver disease, drug-induced liver injury, alcoholic liver disease, genetic metabolic liver disease, etc.)； Accompanied with human immunodeficiency virus infection or congenital immune deficiency diseases; Accompanied with severe diabetes, autoimmune diseases etc. and other important organ dysfunctions; Patients who fail to comply with this research arrangement and sign an informed consent form Patients can not follow-up; Investigator considering inappropriate.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Shu Zhu, Master
Phone
+8615626477267
Email
zhush8@mail2.sysu.edu.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Peng, ph.D.
Organizational Affiliation
Third Affiliated Hospital, Sun Yat-Sen University
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Xu, ph.D.
Organizational Affiliation
Third Affiliated Hospital, Sun Yat-Sen University
Official's Role
Study Director
Facility Information:
Facility Name
Third Affiliated Hospital of Sun Yat-sen University
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510630
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Liang Peng, Doctor
Phone
+8613533978874
Email
pzp33@hotmail.com

12. IPD Sharing Statement

Plan to Share IPD
No

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Optimized Treatment of Peginterferon Alfa 2a in Treatment Experienced Patients With HBV Related Liver Fibrosis

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