Stopping TDF Treatment After Long Term Virologic Suppression in HBeAg-negative CHB
Condition: Chronic Hepatitis B
MeSH terms: Hepatitis B; Hepatitis B, Chronic; Hepatitis; Hepatitis, Chronic
Intervention: TDF; Stop TDF
Intervention description: Tenofovir disoproxil fumarate (TDF) 300 mg tablet administered orally once daily; Participants will stop TDF therapy
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 43.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: stopping oral antiviral therapy; HBsAg loss; seroconversion; restarting oral antiviral therapy

Summary:

      The primary objective of this study is to evaluate hepatitis B surface antigen (HBsAg) loss
      and seroconversion in participants who stop tenofovir disoproxil fumarate (TDF) (Stop TDF
      arm) compared to participants who continue TDF (Continue TDF arm).

      Only participants who already are on treatment with 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. Participants in the Stop TDF arm will be monitored very closely with special
      focus on biochemical flares (especially alanine aminotransferase (ALT) increases) and
      virological relapses (Hepatitis B viral load increases). If any participant in the Stop TDF
      arm exceeds one or more predefined limits for such flares or relapses, TDF treatment will be
      reinstituted.
    

Eligibility criteria:

        Key Inclusion Criteria:

          -  Chronic hepatitis B, hepatitis B e-antigen negative, hepatitis B e-antibody positive,
             and hepatitis B surface antigen-positive

          -  Hepatitis B e Antigen (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

        Key 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, prothrombin time (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

        Note: Other protocol defined inclusion/Exclusion criteria may apply.