Efficacy & Safety of Tenofovir Disoproxil Fumarate (TDF) Plus Peginterferon α-2a (Peg-IFN) Versus TDF or Peg-IFN Monotherapy in Chronic Hepatitis B
Condition: Chronic Hepatitis B
MeSH terms: Hepatitis A; Hepatitis B; Hepatitis B, Chronic; Hepatitis; Hepatitis, Chronic
Intervention: TDF; Peg-IFN
Intervention description: TDF 300 mg tablets administered orally once daily; Peg-IFN 180 µg administered via subcutaneous injection once weekly
Intervention MeSH terms: Peginterferon alfa-2a
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 751.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Chronic Hepatitis B; Hep B; Non cirrhotic; Tenofovir disoproxil fumarate (TDF); Peginterferon α-2a (Peg-IFN)

Summary:

      The primary objective of this study is to evaluate the efficacy of tenofovir disoproxil
      fumarate (TDF) plus peginterferon α-2a (Peg-IFN) combination therapy for 48 weeks versus
      standard of care TDF monotherapy or Peg-IFN monotherapy for 48 weeks in non-cirrhotic adults
      with chronic hepatitis B virus (HBV) as determined by loss of hepatitis B surface antigen
      (HBsAg).

      The study will consist of 2 phases for participants in the TDF+Peg-IFN 48 Weeks, TDF 48 Weeks
      + Peg-IFN 16 Weeks, and Peg-IFN 48 Weeks groups. Following an initial 48 weeks of treatment,
      participants in these groups will be monitored for 24 weeks for signs of worsening HBV, and
      those meeting TDF retreatment and flare management criteria will be eligible to receive TDF
      monotherapy during a retreatment phase, up to Week 120.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Adults (age 18-75) with chronic HBV (positive for serum hepatitis B surface antigen
             (HBsAg) or HBV DNA for at least 6 months) prior to baseline

          -  Anti-HBV treatment-naive adults; adults who have taken oral anti-HBV nucleoside
             therapy with the last dose ≥ 24 weeks prior to screening are also eligible.

          -  Positive or negative for hepatitis B e antigen (HBeAg)

          -  HBV DNA ≥ 20,000 IU/ml (HBeAg-positive participants) and ≥ 2,000 IU/ml (HBeAg-negative
             participants)

          -  Alanine aminotransferase (ALT) > 54 U/L and ≤ 400 U/L for men and > 36 U/L and ≤ 300
             U/L for women

          -  Creatinine clearance ≥ 70 mL/min

          -  Negative serum pregnancy test for females of childbearing potential

          -  Sexually active females of childbearing potential must agree to use a
             protocol-recommended method of contraception throughout the study and for 30 days
             following the last dose of study medication

          -  Lactating females must agree to discontinue nursing before initiation of study
             investigational medicinal product

        Exclusion Criteria:

          -  Known bridging fibrosis or cirrhosis and/or decompensated liver disease

          -  Evidence of hepatocellular carcinoma

          -  Significant kidney, heart, lung, neurological, autoimmune disease, or bone disease
             (eg, osteomalacia,chronic osteomyelitis, osteogenesis imperfecta, osteochondrosis,
             multiple bone fractures)

          -  Absolute neutrophil count < 1,500/mm^3, platelet < 100,000/mm^3, hemoglobin < 10 g/dL
             (female) or < 11 g/dL (male)

          -  History of severe depression or severe psychiatric disease

          -  Thyroid dysfunction

          -  Coinfection with HIV, hepatitis C virus (HCV) or hepatitis D virus (HDV)

          -  Pregnant