Lamivudine Extending Therapy in Chronic Hepatitis B Patients After 3-year of Oral Antiviral Agents

Chronic Hepatitis B Clinical Trial

Official title:

A Prospective, Open-label, Multicenter Study of Lamivudine Extending Therapy in Chronic Hepatitis B Patients After 3-year of Oral Antiviral Agents

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02337127
• Other study ID #: KMUH-IRB-20110187
• Status: Recruiting
• Phase: Phase 4
• First received: December 1, 2014
• Last updated: January 8, 2015
• Start date: June 2011
• Est. completion date: May 2016

Study information

• Verified date: January 2015
• Source: Kaohsiung Medical University Chung-Ho Memorial Hospital
• Contact: Wan-Long Chuang
• Email: waloch[@]kmu.edu.tw
• Is FDA regulated: No
• Health authority: Taiwan : Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Current treatment guidelines indicate that oral antiviral agents for HBeAg-positive chronic hepatitis B virus infection (CHB) can be stopped if the patient has undergone HBeAg seroconversion with HBV-DNA loss measured at two consecutive occasions at least 6 months apart (primary treatment endpoint). Stopping treatment can be considered if undetectable HBV-DNA has been documented on three separate occasions 6 months apart in HBeAg-negative patients. However, oral antiviral drugs currently approved for the treatment of CHB have relatively limited sustained long-term efficacy and a large proportion of patients will suffer from HBV recurrence after stopping treatment.

Description:

The purposes of this study are:

1. To evaluate the long-term efficacy of Lamivudine extending therapy in CHB patients who received at least 3-year of oral antiviral agents.

2. To evaluate the long-term outcomes and predictive factors of Lamivudine extending therapy in CHB patients who received at least 3-year of oral antiviral agents.

A prospective, open-label, multicenter study will enroll 500 treatment-naïve CHB patients who received at least 3-year of oral antiviral agents. With their voluntary decision after consultation, 250 patients will receive Lamivudine extending therapy for 5 years and the other 250 patients will receive follow-up and serve as controls. The primary outcome measurement is HBV DNA recurrence, whilst the secondary outcome measurement is liver-related outcomes and associated predictive factors

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 500
• Est. completion date: May 2016
• Est. primary completion date: May 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Male and female patients >=18 years of age

2. Negative serum HBV DNA within 3 months prior to entry

3. ALT <1.5 ULN within 3 months prior to entry

4. 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. Additionally, all fertile males with partners of childbearing age and females of the Lamivudine treatment arm must be using reliable contraception during the study and for 6 months after treatment completion.

Exclusion Criteria:

1. Women with ongoing pregnancy or breast feeding

2. Therapy with any systemic anti-neoplastic or immunomodulatory treatment (including supraphysiologic doses of steroids and radiation) *6 months prior to the first dose of study drug

3. Any investigational drug *6 weeks prior to the first dose of study drug

4. Co-infection with active hepatitis A, hepatitis C and/or human immunodeficiency virus (HIV)

5. Patients who have virological evidence of Lamivudine-associated YMDD mutants.

6. Patients who have clinical evidence of liver cirrhosis or hepatocellular carcinoma.

7. History or other evidence of a medical condition associated with chronic liver disease other than HCV (e.g., hemochromatosis, autoimmune hepatitis, metabolic liver disease, alcoholic liver disease, toxin exposures)

8. Signs or symptoms of hepatocellular carcinoma

9. History or other evidence of bleeding from esophageal varices or other conditions consistent with decompensated liver disease

10. Neutrophil count <1500 cells/mm3 or platelet count <90,000 cells/mm3 at screening

11. Serum creatinine level >1.5 times the upper limit of normal at screening

12. History of severe psychiatric disease, especially depression. Severe psychiatric disease is defined as treatment with an antidepressant medication or a major tranquilizer at therapeutic doses for major depression or psychosis, respectively, for at least 3 months at any previous time or any history of the following: a suicidal attempt, hospitalization for psychiatric disease, or a period of disability due to a psychiatric disease

13. History of a severe seizure disorder or current anticonvulsant use

14. History of immunologically mediated disease, chronic pulmonary disease associated with functional limitation, severe cardiac disease, major organ transplantation or other evidence of severe illness, malignancy, or any other conditions which would make the patient, in the opinion of the investigator, unsuitable for the study

15. Evidence of drug abuse (including excessive alcohol consumption) within one year of study entry

16. Inability or unwillingness to provide informed consent or abide by the requirements of the study

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Hepatitis B
• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• Lamivudine
Lamivudine, 100mg/day, per os

Locations

Country	Name	City	State
Taiwan	Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital	Kaohsiung	NRW

Sponsors (1)

Lead Sponsor	Collaborator
Kaohsiung Medical University Chung-Ho Memorial Hospital

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Rate of severe reactivation or death	severe reactivation means alanine aminotransferase (ALT) > 10 fold upper limit of normal plus either total bilirubin > 2 mg/dL or prothrombin time prolong > 3 seconds	up to 12 months	Yes
Primary	Rate of HBV DNA recurrence		up to 12 months	No
Secondary	Associated predictive factors of HBV DNA recurrence		up to 12 months	No
Secondary	Rate of drug resistant mutation		up to 12 months	No
Secondary	Rate of clinical relapse in Group B (non-intervention)	clinical relapse means HBV DNA>2000 IU/mL plus ALT > 2 fold upper limit of normal (ULN) in end of entecavir (ETV) normal alanine aminotransferase (ALT) or 2 fold elevation in end of ETV abnormal ALT patients	up to 12 months	No