Stopping TDF Treatment After Long Term Virologic Suppression in HBeAg-negative CHB (FINITE CHB)

• Seroconversion [ Time Frame: At Weeks 96 and 144 ] [ Designated as safety issue: No ]
  The proportion of subjects with seroconversion at Weeks 96 and 144 and will be summarized the same way as for the primary endpoint of proportion of subjects with HBsAg loss at Week 144
• Restarting Therapy [ Time Frame: At Weeks 48, 96 and 144 ] [ Designated as safety issue: No ]
  The proportion of subjects who restart TDF therapy in Arm A (stop) at Weeks 48, 96 and 144 will be estimated using the Kaplan-Meier (KM) product limit method. Subjects who have not re-started TDF therapy but discontinue from the study will be considered as censored at the last laboratory collection date.

Withdrawal of antiviral therapy can result in hepatic or alanine aminotransferase (ALT) flares as Hepatitis B Virus (HBV) replication resumes; however, in some patients, a flare exacerbates chronic hepatitis temporarily but can also result in viral clearance. Hepatic flares are common after stopping anti-HBV therapy.

Only patients who already are on treatment with tenofovir disoproxil fumarate (TDF) monotherapy or TDF in combination with lamivudine or emtricitabine for at least 4 years and who achieved and maintained virologic suppression (< 400 copies/mL) for 3.5 or more years will be included in this study. One treatment arm will stop the TDF therapy while the other treatment arm will continue the TDF therapy.

Patients who stop TDF (Arm A) will be monitored very closely with special focus on biochemical flares (especially ALT increases) and virological relapses (Hepatitis B viral load increases). If any subject in the stop therapy arm exceeds one or more predefined limits for such flares or relapses, TDF will be reinstituted.

The study will assess Hepatitis B surface antigen (HBsAg) loss (i.e. specific Hepatitis B virus components are no longer detectable) and seroconversion (occurrence of Hepatitis B surface antibody, a specific antibody which usually occurs after HBsAg loss) rates during study duration. The percentage of patients who need to restart TDF therapy in the stop arm will also be evaluated.

• Experimental: Arm A (stop TDF)
  Subjects randomized to this arm will stop TDF therapy at baseline
  Intervention: Drug: Stopping TDF therapy
• No Intervention: Arm B (continue TDF)
  Subjects randomized to this arm will continue their usual TDF therapy

Inclusion Criteria:

• Chronic hepatitis B, hepatitis B e-antigen negative, hepatitis B e-antibody positive, and hepatitis B surface antigen-positive
• HBeAg-negative at the beginning of TDF therapy (i.e. TDF monotherapy or combination of TDF + lamivudine or TDF + emtricitabine)
• Received continuous TDF therapy (i.e. TDF monotherapy or combination of TDF + lamivudine or TDF + emtricitabine) treatment for at least 4 years prior to screening. If TDF has been used in combination with lamivudine or emtricitabine, lamivudine or emtricitabine must have been stopped at least 12 weeks prior to screening
• Documented hepatitis B virus DNA (HBV DNA) < 400 copies/mL for at least 3.5 years prior to screening and at screening
• ALT within normal range
• α-fetoprotein (AFP) <= 50 ng/mL
• Calculated creatinine clearance >= 70 mL/min by Cockcroft-Gault formula using ideal body weight
• <= 10 kPa on Fibroscan assessment
• A negative serum pregnancy test for female subjects
• Adult subjects >= 18 years of age

Exclusion Criteria:

• Known cirrhosis
• Evidence of fibrosis >= Stage 3 (METAVIR) on liver biopsy or Fibroscan > 10 kPa within 6 months prior to screening
• Documentation of confirmed episodes (i.e., 2 consecutive values) of HBV DNA > 400 copies/mL within 3.5 years prior to screening
• History of decompensated liver disease (defined as direct [conjugated] bilirubin > 1.5 x upper limit of normal, PT > 1.5 x upper limit of normal, platelets < 75,000/mm³, serum albumin < 3.0 g/dL
• History of clinical hepatic decompensation in the judgement of the investigator
• Evidence of hepatocellular carcinoma
• Significant bone disease (in the judgment of the investigator)
• Serological evidence of coinfection with human immunodeficiency virus (HIV), hepatitis C virus, or hepatitis D infection
• Known hypersensitivity to TDF, its metabolites, or formulation excipients
• Concomitant therapy with disallowed medications
• History of malignant disease
• Lactating females
• Females wishing to became pregnant during the duration of the stud
• Subjects participating in another clinical trial can only be enrolled at the discretion of the Medical Monitor