Telbivudine or Tenofovir Treatment in HBeAg-negative Chronic Hepatitis B Patients Based on the Roadmap Concept (LDT600A)

Inclusion criteria:

• Written informed consent must be obtained before any assessment is performed.
• Male or female ≥18 years of age.
• Documented compensated HBeAg negative CHB defined by all of the following:
• Detectable serum HBsAg at the screening visit and at least 6 months prior to the screening visit.
• HBeAg negative at the screening visit with positive HBeAb.
• Serum HBV DNA > 2000 IU/mL, as determined by the COBAS Taqman HBV DNA PCR assay at the central laboratory at screening visit.
• Serum ALT level > 1×ULN and < 10×ULN at the screening visit.
• Available liver histology report within 12 months before screening with diagnosis of chronic hepatitis B.
• Patient is willing and able to comply with the study drug regimen and all other study requirements

Exclusion criteria:

• History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes.
• Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive beta-HCG laboratory test (> 5 mIU/mL).
• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, including women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner and women whose partners have been sterilized by vasectomy or other means, UNLESS they are using two birth control methods. The two methods can be a double barrier method or a barrier method plus a hormonal method.
• Adequate barrier methods of contraception include: diaphragm, condom (by the partner),intrauterine device (copper or hormonal), sponge or spermicide. Hormonal contraceptives include any marketed contraceptive agent that includes an estrogen and/or a progestational agent.
• Fertile males, defined as all males physiologically capable of conceiving offspring, UNLESS the female partner meets the following definition of post-menopausal: 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels > 40 mIU/ml (IU/L) or the patient must agree to use two methods of birth control. This is any combination of hormonal contraception (implantable, patch, oral or injection), IUD, male or female condom with spermicidal gel, diaphragm, sponge or cervical cap.
• Patients co-infected with HCV, HDV, or HIV.
• Patient has received treatment of nucleoside or nucleotide drugs whether approved or investigational at any time.
• Patient has received IFN or other immunomodulatory treatment within six months before the screening visit. Precluded therapies include, but are not limited to any exposure to any types of interferons, Thymosin, IL-12, or other putative systemic immunomodulation.
• Patient has a medical condition that requires frequent use of systemic acyclovir or famcyclovir, etc.
• Patient has a medical condition that requires frequent use of systemic corticosteroids, however topical and inhaled corticosteroids are allowed (Appendix 2).
• Patient has clinical signs/symptoms of hepatic decompensation with Child-Pugh score of B or C.
• History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases. Patients, who have ultrasonographic findings of hepatic mass and/or elevated AFP suggestive of possible HCC prior to enrollment, should have the disease ruled-out prior to entrance into the study.
• Patient has one or more additional known primary or secondary causes of liver disease, other than CHB, including steatohepatitis and autoimmune hepatitis among other liver diseases. Note: Gilbert's syndrome and Dubin-Johnson syndrome are not considered exclusion criteria for this study.
• Patient is currently abusing illicit drugs, or has a history of illicit substance abuse within the preceding two years.
• Patients with a history of alcohol abuse will be required to be abstinent from alcohol 6 months prior to screening or at the investigator's discretion, and during the course of the study.
• Patients without a history of alcohol abuse are required to have a alcohol consumption of ≤ 30g ethanol/day for men and ≤ 15g ethanol/day for women twice a week during the course of the study.
• Patient has a history of clinical and laboratory evidence of chronic renal insufficiency defined as an estimated serum creatinine clearance < 50 mL/min using either Cockcroft-Gault or MDRD; or with a lower serum phosphate < 1.5 mg/dL.
• Patient has a medical condition requiring the chronic or prolonged use of potentially hepatotoxic drugs or nephrotoxic drugs.
• Patient has a medical condition requiring the use of chemotherapy .
• History of any other acute or chronic medical condition that in the opinion of the investigator would make the patient unsuitable for inclusion into the study.
• Patient has any other concomitant medical or social condition likely to preclude compliance with the schedule of evaluations in the protocol, or likely to confound the efficacy or safety observations of the study (e.g., concurrent malignancies,unstable angina, myocardial infarction or heart failure, uncontrolled asthma or diabetes, unstable thyroid disease or other significant hormonal conditions, uncontrolled seizure disorders, severe psychiatric disorders, active tuberculosis under current treatment, etc.)
• Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer.
• Patient has a history of myopathy, myositis, or persistent muscle weakness.
• Patient has any of the following laboratory values during Screening:
• Hemoglobin < 11 g/dL (110g/L) for men or < 10 g/dL (100g/L) for women
• Total WBC < 3,500/mm3 (3.5×109/L)
• Absolute neutrophil count (ANC) < 1,500/mm3 (1.5×109/L)
• Platelet count < 75,000/mm3 (75×109/L)
• Serum amylases or lipase ≥ 2×ULN

Other protocol-defined inclusion/exclusion criteria may apply