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

Hepatitis B Clinical Trial

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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03957629
• Other study ID #: PL7
• Status: Recruiting
• Phase: N/A
• Start date: November 6, 2019
• Est. completion date: July 30, 2023

Study information

• Verified date: January 2020
• Source: Third Affiliated Hospital, Sun Yat-Sen University
• Contact: Shu Zhu, Master
• Phone: +8615626477267
• Email: zhush8[@]mail2.sysu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 186
• Est. completion date: July 30, 2023
• Est. primary completion date: July 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Fibrosis
• Hepatitis
• Hepatitis B
• Liver Cirrhosis
• Liver Fibrosis

Intervention

Drug:
• Tenofovir Disoproxil Fumarate
Oral medication of Tenofovir Disoproxil Fumarate 300mg once per day.
• PEG-Interferon alfa 2a
Subcutaneous injection of Peginterferon Alfa-2a 180 µg once per week.

Locations

Country	Name	City	State
China	Third Affiliated Hospital of Sun Yat-sen University	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Third Affiliated Hospital, Sun Yat-Sen University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	48 weeks; 96 weeks
Secondary	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.	24 week, 48 week, 72 week, 96 week
Secondary	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.	24 week, 48 week, 72 week, 96 week
Secondary	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.	24 week, 48 week, 72 week, 96 week