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

• Register: ClinicalTrials.gov
• Last refreshed on: 21 January 2013
• Main ID: NCT01379508
• Date of registration: 21/06/2011
• Primary sponsor: Novartis Pharmaceuticals
• Public title: Telbivudine or Tenofovir Treatment in HBeAg-negative Chronic Hepatitis B Patients Based on the Roadmap Concept LDT600A
• Scientific title: A Randomized, Open-label, 104-week Treatment Study to Evaluate the Efficacy and Safety of Telbivudine or Tenofovir Treatment in HBeAg-negative Chronic Hepatitis B Patients Based on the Roadmap Concept
• Date of first enrolment: March 2011
• Target sample size: 240
• Recruitment status: Recruiting
• URL: http://clinicaltrials.gov/show/NCT01379508
• Study type: Interventional
• Study design: Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Countries of recruitment

Austria, Bulgaria, Germany, Greece, Italy, Russian Federation, Spain

Key inclusion & exclusion criteria

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



Age minimum: 18 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Chronic Hepatitis

Intervention(s)

Drug: oral antiviral for HBV

Drug: tenofovir disoproxil fumarate

Primary Outcome(s)

The primary objective of the study is to compare the efficacy of Roadmap-Concept-based telbivudine treatment versus Roadmap-Concept-based tenofovir treatment in HBeAg-negative CHB patients [Time Frame: 52 weeks]

Secondary Outcome(s)

To assess the antiviral efficacy, as evaluated by rate of patients achieving HBV DNA <300 copies/mL (51 IU/mL) [Time Frame: 104 weeks]

To assess the antiviral efficacy, as evaluated by serum HBV DNA reduction from baseline, and time to achieve HBV DNA < 300 copies/mL (51 IU/mL). [Time Frame: over the course of the study]

To assess the biochemical efficacy as evaluated by rate of patients with ALT normalization [Time Frame: Week 52 and 104 in patients with elevated ALT at baseline.]

To assess the rate of HBsAg loss and HBsAg seroconversion (defined as loss of HBsAg and development of HBsAb) over the course of the study [Time Frame: over the course of the study]

To assess the safety endpoints as evaluated by incidence of death, AE, SAE, AESI and graded laboratory abnormalities [Time Frame: at Weeks 52 and 104]

Secondary ID(s)

CLDT600A2409

Source(s) of Monetary Support

Please refer to primary and secondary sponsors