Use of TDF in Patients With Inactive Chronic Hepatitis B Infection

Sponsor

University Health Network, Toronto (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT02600117

Collaborator

Gilead Sciences (Industry)

Enrollment

Location

Arm

83.2

Anticipated Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Recent evidence suggests that patients with inactive chronic hepatitis B (CHB) may develop the same types of liver complications that patients in the active state of hepatitis B virus (HBV) infection experience. Treatment guidelines for patients in the active state of HBV infection indicate that HBsAg clearance is associated with definitive remission of the activity of chronic HBV & improved long-term outcome. Clinical data showed that HBsAg clearance is achievable, in a small population of patients on continuous treatment with potent oral antivirals (OAVs), such as tenofovir disoproxil fumarate (TDF). It is possible the same OAVs can have the same effect in patients with inactive CHB, but in a shorter treatment duration. The purpose of this study is to find out if TDF is effective in controlling HBV DNA & promoting seroconversion from HBsAg-positive to HBsAb-positive in patients with inactive CHB.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis B, Chronic	Drug: Tenofovir disoproxil fumarate	Phase 3

Detailed Description

Hepatitis B virus (HBV) infection is a major worldwide health problem. The course of the majority of patients with inactive chronic hepatitis B is usually benign; therefore, the current treatment guidelines recommend not treating these patients. However, recent evidence suggests that the prognosis of these inactive carrier is not exactly benign. For instance, patients may develop liver cancer despite their inactive carrier state. Also, approximately 20-30% of patients with inactive chronic hepatitis B may undergo spontaneous reactivation of hepatitis over time. Multiple episodes of reactivation or sustained reactivation can cause progressive liver damage and even liver decompensation. However, until there are data to support that treatment with oral antivirals can alter the outcome of these patients, they will remain untreated. Potent oral antivirals have been shown to suppress HBV DNA and normalize liver enzymes in patients with active chronic hepatitis B infection. With continued long-term treatment, some of these patients have gone on to clear hepatitis B surface antigen and develop hepatitis B surface antibody. Therefore, it is possible that the same oral antivirals can have the same effect in patients with inactive chronic hepatitis B, but in a shorter duration of treatment. This study will explore the possible use of tenofovir disoproxil fumarate in controlling HBV DNA and promoting hepatitis B surface antigen seroconversion in patients with inactive chronic hepatitis B.

After completion of all initial investigations, patients will be started on TDF 300mg daily. Patients will be reviewed at 6 monthly intervals as per standard of care. At each clinic visit, patients will have blood tests including complete blood count, renal function, electrolytes, liver enzyme and liver function tests, as well as HBV serology including quantitative HBsAg and HBV DNA. Patients will also receive an abdominal ultrasound, fibroscan and fibrotest on an annual basis. Treatment will be stopped when sAg+ve seroconverts to sAb+ve or at the end of 3 years whichever comes earlier.

Study Design

Study Type:

Interventional

Actual Enrollment :

50 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

The Use of Tenofovir Disoproxil Fumarate (TDF) in the Management of Patients With Inactive Chronic Hepatitis B (CHB) Infection

Actual Study Start Date :

Jan 26, 2016

Anticipated Primary Completion Date :

Jun 1, 2022

Anticipated Study Completion Date :

Jan 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Other: Tenofovir disoproxil fumarate 300 mg, orally, once a day for 3 years or when sAg+ve seroconverts to sAb+ve whichever comes earlier	Drug: Tenofovir disoproxil fumarate 300 mg, oral, once a day Other Names: Viread

Arm

Intervention/Treatment

Other: Tenofovir disoproxil fumarate

300 mg, orally, once a day for 3 years or when sAg+ve seroconverts to sAb+ve whichever comes earlier

Drug: Tenofovir disoproxil fumarate

300 mg, oral, once a day

Other Names:

Viread

Outcome Measures

Primary Outcome Measures

Seroconversion from hepatitis B surface antigen positive to hepatitis B surface antibody positive [Three years]
Positive hepatitis B surface antibody result will indicate recovery from chronic hepatitis B virus infection.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

All patients with inactive chronic hepatitis B, defined as someone who has HBV DNA ≤ log4, eAg-ve, eAb+, HBsAg+ve and normal ALT persistently for >6 months

Exclusion Criteria:

Patients older than 75 years of age
Presence of hepatoma at entry
Presence of decompensated cirrhosis defined by a history of variceal bleed, ascites, or hepatic encephalopathy
Presence of abnormal renal function defined as serum creatinine of>110µmol/L
co-infection with HIV

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University Health Network - Toronto General Hospital	Toronto	Ontario	Canada	M5G 2C4

Sponsors and Collaborators

University Health Network, Toronto
Gilead Sciences

Investigators

Principal Investigator: Florence Wong, MD, University Health Network -Toronto General Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Florence Wong, MD, Hepatologist, Professor-Division of Gastroenterology,Department of Medicine, University of Toronto, University Health Network, Toronto

ClinicalTrials.gov Identifier:

NCT02600117

Other Study ID Numbers: