Tenofovir Disoproxil Fumarate (TDF) 300mg 3 Years RD Therapy Chinese Chronic Hepatitis B (CHN) CHB Multiple Nucleos(t)Ide Analogues (NAs) Failure Points Pts PH4 PMS Study
Condition: Hepatitis B, Chronic
MeSH terms: Hepatitis A; Hepatitis B; Hepatitis B, Chronic; Hepatitis; Hepatitis, Chronic
Intervention: Tenofovir disoproxil fumarate
Intervention description: Tenofovir disoproxil fumarate tablets supplied will be white, almond-shaped, film-coated tablets containing 300 mg of TDF. Each tablet contains the following inactive ingredients: microcrystalline cellulose, lactose monohydrate, pregelatinised starch, croscarmellose sodium, and magnesium stearate.
Intervention MeSH terms: Tenofovir
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 213.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Chronic Hepatitis B; Tenofovir disoproxil fumarate; Failure of multiple NAs treatment

Summary:

      This is a phase IV, single-arm, open-label, multi-centre study to assess the efficacy of TDF
      in Chronic hepatitis B (CHB) subjects following failure of multiple Nucleos(t)ide analogues
      (NAs). The study will enrol 200 CHB subjects following failure of multiple NAs. Subjects will
      be assessed for eligibility at a screening visit, with eligible subjects returning for a
      baseline assessment after approximately 4 weeks (Screening phase). In the treatment phase all
      enrolled subjects will receive open label TDF at a dose of 300 milligrams (mg) orally once
      daily. All the eligible study subjects will undergo safety and efficacy assessments every 12
      weeks for a total of 14 visits. Tenofovir disoproxil fumarate, the oral pro-drug of tenofovir
      (TFV), is a nucleotide analogue that inhibits viral polymerases by direct binding and after
      incorporation into deoxyribonucleic acid (DNA), by termination of the DNA) chain. TDF is a
      highly potent treatment in treatment-naïve and lamivudine (LAM) resistant CHB patients. The
      purpose of our study is to evaluate the efficacy of TDF treatment in Chinese CHB patients
      following failure of multiple NAs. In addition, the study will also explore the relationship
      of baseline factors and early HBV DNA suppression to long-term virological response. The
      efficacy of TDF in multi-drug resistant patients will be analysed separately. The data
      generated by this study could then be used to optimize the clinical application of TDF and
      provide new evidence for management of the HBV infections following failure of multiple NAs.
      The result of this study will help Chinese physicians better manage the CHB patients
      following failure of multiple NAs.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Aged between 18-65years (inclusive). Male or female; a female is eligible to enter and
             participate in this study if she is of: Non-childbearing potential (i.e.,
             physiologically incapable of becoming pregnant, including any female who is
             post-menopausal); or,

          -  Child-bearing potential, has a negative serum pregnancy test at baseline, and agrees
             to one of the following methods for avoidance of pregnancy during the period of the
             study and until 30 days after last dose of study medication: Oral contraceptive,
             either combined or progestogen alone, Injectable progestogen, Implants of
             levonorgestrel, Oestrogenic vaginal ring, Percutaneous contraceptive patches.,
             Intrauterine device (IUD) or intrauterine system (IUS) showing that the expected
             failure rate is less than 1% per year as stated in the IUD or IUS product label, Has a
             male partner who is sterilised, Double barrier method: condom and an occlusive cap
             (diaphragm or cervical/vault caps) with a vaginal spermicidal agent (foam/gel/film
             /cream/suppository).

          -  The ability to understand and sign a written informed consent prior to any
             study-related procedure and comply with the requirements of the study.

          -  Positive HBsAg for more than 6 months, and anti-HBs negative.

          -  Serum HBV DNA level >=200 IU/mL at study screening (Use central lab results).

          -  Experienced multiple NAs treatment failure which is defined as HBV DNA greater than
             200 IU/mL after at least two NAs treatment (at least 6 months continuous treatment for
             each NA(s), total duration is no less than 12 months). In addition, subjects judged by
             the treating physician to have adhered to previous NA therapy.

          -  Agreement not to participate in any other investigational trials or to undertake other
             HBV systemic antiviral or interferon (IFN) regimens during participation in this
             study.

        Exclusion Criteria:

          -  Hepatocellular carcinoma as evidenced by one of the following: Suspicious foci on
             ultrasound or radiological examination, Normal ultrasound but a history of rising
             serum alpha-fetoprotein and serum alpha-fetoprotein >20 nanogram (ng) per mL at
             screening.

          -  Clinical signs of decompensated liver disease at baseline. These may include but are
             not limited to:Total serum bilirubin >1.5 x Upper limit of the normal range (ULN),
             International Normalized Ratio >1.3, Serum albumin <32grams per Liter (g/L), History
             of clinical hepatic decompensation (e.g., ascites, variceal bleeding, or
             encephalopathy).

          -  Creatinine clearance less than 70 milliliter per minutes (mL/min).

          -  Alanine aminotransferase >10 times ULN at screening or history of acute exacerbation
             leading to transient decompensation.

          -  Haemoglobin <8 grams per deciliter (g/dL), absolute neutrophil count <1.0 x 10^9 per
             Liter, platelets <75 x 10^9 per Liter.

          -  Documented co-infection with hepatitis A (HAV), hepatitis C (HCV), hepatitis delta
             virus (HDV), hepatitis E virus (HEV) or Human immunodeficiency virus (HIV). For HCV
             co-infection, subjects who are anti-HCV positive and in whom HCV RNA is undetectable
             are considered to be not eligible for enrolment.

          -  Evidence of active liver disease due to autoimmune hepatitis (antinuclear antibody
             titre >1:160)

          -  Any serious or active medical or psychiatric illnesses other than hepatitis B which,
             in the opinion of the Investigator, would interfere with subject treatment, assessment
             or compliance with the protocol. This would include any uncontrolled clinically
             significant renal, cardiac, pulmonary, vascular, neurogenic, digestive, metabolic
             (diabetes, thyroid disorders, adrenal disease), immunodeficiency disorders,
             pathological fractures or cancer.

          -  Active alcohol or drug abuse or history of alcohol or drug abuse considered by the
             Investigator to be sufficient to hinder compliance with treatment, participation in
             the study or interpretation of results.

          -  A female who is breastfeeding or plan to breast.

          -  Use of immunosuppressive therapy, immunomodulatory therapy [including Pegylated
             interferon (PEG-IFN) and short-acting interferon or thymosin alpha], systemic
             cytotoxic agents within the previous 6 months prior to screening.

          -  Planned for liver transplantation or previous liver transplantation.

          -  Receipt of TDF within 6 months prior to screening.

          -  Therapy with nephrotoxic drugs (e.g., aminoglycosides, amphotercin B, vancomycin,
             cidofovir, foscarnet, cis-platinum, pentamidine etc.) or competitors of renal
             excretion (e.g., probenecid) within 2 months prior to study screening or the
             expectation that subject will receive any of these during the course of the study.

          -  History of hypersensitivity to nucleoside and/or nucleotide analogues and/or any
             component of study medication.

          -  Inability to comply with study requirements as determined by the study Investigator.