Study on an Optimal Antiviral Treatment in HBeAg Positive Chronic Hepatitis B Patients

NCT03013556 | Unknown Phase 4

• 1 other identifier: SHDC12016101
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 8

Brief Summary

The current study is a prospective, randomized, open, multi-center investigation. The aim of the study is to investigate whether the HBeAg seroconversion rate can be improved if applying combination therapy in HBeAg positive CHB patients who has achieved HBVDNA\<105copies/ml，HBsAg≤5000IU/ml, ALT≥ 2ULN or Liver histology G2S2.

Conditions

Chronic Hepatitis

Keywords

HBeAg positive

Outcome Measures

Primary Outcomes (1)

• Number of subjects who achieve HBeAg seroconversion

  The number of subjects with HBeAg seroconversion at week 96 will be measured

  at 96 week

Secondary Outcomes (6)

• Number of participants who achieve HBeAg seroconversion

  at 48 week;at 72 week

• The percentage decrease of HBsAg level at group A,B,C

  at 48 week;at 72 week;at 96 week

• Number of participants who achieve HBeAg loss

  at 48 week;at 72 week;at 96 week

• The number of subjects who achieve HBVDNA undetectable

  at 24 week;48 week;at 72 week;at 96 week

• The factor such as HBsAg level related to responsible rate

  at week 48,72,96

Study Arms (3)

Group A,TDF

ACTIVE COMPARATOR

The subjects in group A will be treated by TDF for 96 weeks

Drug: Group A, TDF

Group B,TDF+PEG

EXPERIMENTAL

The subjects in group B will be treated by TDF in the first 48 weeks, then will be treated by the combination of TDF and Peginterferon alfa-2a for another 48 weeks

Drug: Group B:TDF then TDF and Peginterferon alfa-2a

Group C,TDF+PEG

EXPERIMENTAL

The subjects in group C will be treated by the combination of TDF and Peginterferon alfa-2a for the first 48 weeks, then will be treated by TDF for another 48 weeks

Drug: Group C:TDF and Peginterferon alfa-2a then TDF

Interventions

Group A, TDF DRUG

TDF for 96 weeks

Also known as: tenofovir

Group A,TDF

Group B:TDF then TDF and Peginterferon alfa-2a DRUG

Subjects will be treated by TDF in the first 48 weeks, then will be treated by the combination of TDF and Peginterferon alfa-2a for another 48 weeks

Also known as: tenofovir,pegasys

Group B,TDF+PEG

Group C:TDF and Peginterferon alfa-2a then TDF DRUG

Subjects will be treated by the combination of TDF and Peginterferon alfa-2a for the first 48 weeks, then will be treated by TDF for another 48 weeks.

Also known as: tenofovir,pegasys

Group C,TDF+PEG

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female patients with age ≥18 and ≤65 years;
• There should be evidences that HBsAg and HBeAg have been positive for more than 6 months with HBsAb and HBeAb negative;HBsAg≤50000IU/ml, ALT≥ 2ULN,Liver histology above G2S2 and HBV DNA≥10\*5 copies/mL;
• Women without ongoing pregnancy or breast feeding and both women and men willing to take an effective contraceptive measure during the treatment;
• Agree to participate in the study and sign the patient informed consent form.

You may not qualify if:

• Treated by immunosuppressant,immunomodulator,Systemic cytotoxic drug,herbs or HBIg within 6 months prior to the first dose of treatment;
• ALT≥10 X ULN or total bilirubin ≥2 X ULN;
• Allergic history to interferon;
• Co-infection with active hepatitis A, hepatitis C, hepatitis D and/or human immunodeficiency virus (HIV);
• Child-Pugh scores \>7;
• 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);
• Pregnant or breast-feeding Women;
• Consuming alcohol in excess of 20g/day for women and 30g/day for men within 6 months prior to enrollment or drug taking history;
• ANC(absolute neutrophil count)\<1.5x 10\^9/L or PLT(platelet count)\<90x 10\^9/L
• Creatinine over upper limit of normal;
• History of severe psychiatric disease, especially depression. Severe psychiatric disease is defined as major depression or psychosis that treated with antidepressant medication or a major tranquilizer at therapeutic doses respectively at any time prior to 3 months 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 immunologically mediated disease, (e.g., inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, scleroderma, rheumatoid arthritis etc.);
• History of esophageal varices bleeding or other evidence of esophageal varices bleeding or other symptoms consistent with decompensated liver disease;
• History of severe cardiac disease (e.g., New York Heart Association Functional Class III or IV, myocardial infarction within 6 months, ventricular tachyarrhythmias requiring ongoing treatment, unstable angina or other significant cardiovascular diseases);
• Hemodialysis patients or patients with renal insufficiency;

Sponsors & Collaborators

• Ruijin Hospital: lead

Study Sites (8)

Xixi Hospital of Hangzhou

Hangzhou, China

RECRUITING

Changhai Hospital

Shanghai, China

RECRUITING

Hua shan Hospital,Fudan University

Shanghai, China

RECRUITING

Infectious diesease hospital of Huangpu district in Shanghai

Shanghai, China

RECRUITING

No.9 hospital of shanghai

Shanghai, China

RECRUITING

Shanghai public health clinical center

Shanghai, China

RECRUITING

Shuguang Hospital of Shanghai T.C.M

Shanghai, China

RECRUITING

Tongren hospital Shanghai Jiaotong University School of medicine

Shanghai, China

RECRUITING

Related Publications (3)

• Marcellin P, Ahn SH, Ma X, Caruntu FA, Tak WY, Elkashab M, Chuang WL, Lim SG, Tabak F, Mehta R, Petersen J, Foster GR, Lou L, Martins EB, Dinh P, Lin L, Corsa A, Charuworn P, Subramanian GM, Reiser H, Reesink HW, Fung S, Strasser SI, Trinh H, Buti M, Gaeta GB, Hui AJ, Papatheodoridis G, Flisiak R, Chan HL; Study 149 Investigators. Combination of Tenofovir Disoproxil Fumarate and Peginterferon alpha-2a Increases Loss of Hepatitis B Surface Antigen in Patients With Chronic Hepatitis B. Gastroenterology. 2016 Jan;150(1):134-144.e10. doi: 10.1053/j.gastro.2015.09.043. Epub 2015 Oct 8.

  PMID: 26453773 RESULT

• Xie Q, Zhou H, Bai X, Wu S, Chen JJ, Sheng J, Xie Y, Chen C, Chan HL, Zhao M. A randomized, open-label clinical study of combined pegylated interferon Alfa-2a (40KD) and entecavir treatment for hepatitis B "e" antigen-positive chronic hepatitis B. Clin Infect Dis. 2014 Dec 15;59(12):1714-23. doi: 10.1093/cid/ciu702. Epub 2014 Sep 4.

  PMID: 25190434 RESULT

• Brouwer WP, Xie Q, Sonneveld MJ, Zhang N, Zhang Q, Tabak F, Streinu-Cercel A, Wang JY, Idilman R, Reesink HW, Diculescu M, Simon K, Voiculescu M, Akdogan M, Mazur W, Reijnders JG, Verhey E, Hansen BE, Janssen HL; ARES Study Group. Adding pegylated interferon to entecavir for hepatitis B e antigen-positive chronic hepatitis B: A multicenter randomized trial (ARES study). Hepatology. 2015 May;61(5):1512-22. doi: 10.1002/hep.27586. Epub 2015 Feb 27.

  PMID: 25348661 RESULT

MeSH Terms

Conditions

Hepatitis, Chronic

Interventions

Tenofovir; peginterferon alfa-2a

Condition Hierarchy (Ancestors)

Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Xinxin Zhang

  Ruijin Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xinxin Zhang

CONTACT

zhangx@shsmu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: vice president of Ruijin hospital(North collegue)

Study Record Dates

• First Submitted: December 16, 2016
• First Posted: January 6, 2017
• Study Start: November 1, 2016
• Primary Completion: December 30, 2021
• Study Completion: December 31, 2021
• Last Updated: September 22, 2021

Record last verified: 2021-09

Locations

CN (8)