Efficacy of Switching or Adding Pegylated Interferon in Chronic Hepatitis B Patients on Long Term Oral Antiviral Therapy

• Status: Completed
• Trial end date: 2018-12-01
• Target enrollment: 0
• Participant gender: All

Summary

Patients with Chronic Hepatitis B on long term oral antiviral therapy have to continue treatment indefinitely unless they achieve HBeAg seroconversion or HBsAg seroclearance, when therapy can be stopped. While HBeAg seroconversion is a more achievable endpoint, only 20-25% of patients develop this after one year of oral antiviral therapy. HBsAg seroclearance is universally infrequent. Strategies to improve these endpoints such as combination oral antiviral therapy have not been generally successful and recently studies have examined the possibility of switching or adding peginterferon therapy. However these have not been tested adequately in the group of patients that have been on long term oral antiviral therapy. Consequently this study was conceived to evaluate whether switching or adding peginterferon compared to continuing oral antiviral therapy are more efficacious strategies. HBeAg positive and HBeAg negative patients (n=310)will be randomised to continue oral antiviral therapy, switch or add pegylated interferon for 48 weeks in a ratio of 1:2:2 respectively. The study endpoints are HBsAg seroclearance, reduction of qHBsAg >1 log, qHBsAg<200 IU/ml, HBeAg loss and seroconversion, and HBV DNA suppression, all at week 72.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Seng Gee Lim
• Collaborators: Changi General Hospital; Merck Sharp & Dohme Corp.; Singapore Clinical Research Institute; Singapore General Hospital; Tan Tock Seng Hospital
• Treatments: Adefovir; Entecavir; Interferon alpha-2; Interferon-alpha; Interferons; Lamivudine; Peginterferon alfa-2b; Tenofovir

Criteria

Inclusion Criteria:

• Between 21 and 70 years old.

• Documented to be HBsAg positive for ≥ 6 months.

• On any nucleos(t)ide analogue (lamivudine, adefovir, entecavir or tenofovir)for ≥ 1 year

• HBV DNA undetectable by RT PCR at screening

• Patient has agreed not to take any other investigational drug or systemic anti-viral, cytotoxic, corticosteroid, immunomodulatory agents or Chinese traditional remedies unless clinically indicated.

• Patient is able to give written consent prior to study start and to comply with the study requirements.

• Women of childbearing age must have a negative serum (ß-HCG) pregnancy test taken with 14 days of starting therapy

Exclusion Criteria:

• Evidence of decompensated liver disease or hepatocellular carcinoma.

• Have any of the following laboratory tests within 4 weeks of study entry:

• HIV antibody or HCV antibody or HDV antibody positivity

• Absolute neutrophil count < 1.5 X 109/l or platelets < 90 x 109/l or hemoglobin < 13 g/dL for men or 12g/dL for women

• serum albumin <35 g/l or serum bilirubin > 30 mg/l

• creatinine > 1.5 times upper limit of normal

• prothrombin time > 1.5 times control, uncorrected by Vitamin K therapy.

• Any interferon, Immunomodulators, systemic cytotoxic agents, or systemic corticosteroids within 6 months before trial entry.

• Prolonged exposure to known hepatotoxins such as alcohol or drugs.

• History of clinically relevant psychiatric disease, seizures, central nervous system dysfunction, severe pre-existing cardiac, renal, hematological disease or medical illness that in the investigator's opinion might interfere with therapy.

• Malignant disease within 5 years of trial entry.

• Women who are pregnant and who are not practicing adequate birth control measures, or who are lactating