Clinical trial NCT00805675: Effects of Telbivudine and Tenofovir Disoproxil Fumarate Treatment on the Hepatitis B Virus DNA Kinetics in CHB
Official title: A Randomized, Open-label, Controlled, Exploratory Trial to Characterize the Results of Daily Oral Administration of Telbivudine 600 mg and Tenofovir Disproxil Fumarate 300 mg in Combination or Telbivudine 600 mg or Tenofovir Disproxil Fumarate 300 mg Monotherapy Given Over 12 Weeks on the Kinetics of Hepatitis B Virus DNA in Adults With HBeAg Positive Compensated CHB
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hepatitis B Virus
Keywords: Chronic HBV
Asian adult subjects with chronic HBV, in immune tolerant phase, and positive for hepatitis B e antigen (HBeAg)
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2008-12-10
Enrollment: 83
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to compare the safety, tolerability and effectiveness of 12 weeks of treatment with telbivudine 600 mg daily plus tenofovir DF 300 mg one daily (OD) taken together vs. tenofovir DF 300 mg once daily (QD) or vs telbivudine 600 mg monotherapy daily (QD). This is an open labeled, active controlled, viral kinetics study which means the subjects and study doctor will know what study drug subjects have been assigned. This study is open to male and female subjects, \<40 years of age, who have been infected with HBV for at least 6 months and have not received oral treatment for HBV.


Eligibility criteria: Inclusion Criteria:

* Chronic HBV infection, defined as positive serum HBsAg for at least 6 months, or HBsAg positive \> 3 months and negative for IgM anti-HBc and positive for IgG anti-HBc
* Age \< 40 years old
* HBeAg positive
* HBV DNA \> or = to 10\^7 copies/mL by Abbott real-time PCR
* ALT \< or = to 1 ULN
* Willing and able to provide written informed consent
* No prior oral HBV therapy (e.g., nucleotide and/or nucleoside therapy or other investigational agents for HBV infection)
* Is willing and able to comply with the study drug regimen and all other study procedures and requirements
* Is willing and able to provide written informed consent before any study assessment is perform

Exclusion Criteria:

* Decompensated liver disease defined as direct (conjugated) bilirubin \> 1.2 × ULN, PT \> 1.2 × ULN, platelets \< 150,000/mm3, serum albumin \< 3.5 g/dL, or prior history of clinical hepatic decompensation (e.g. ascites, jaundice, encephalopathy, variceal hemorrhage).
* Received interferon (pegylated or not) therapy within 6 months of the screening visit
* α-fetoprotein \> 50 ng/mL
* Evidence of hepatocellular carcinoma (HCC)
* Co-infection with HCV (by serology), or HIV,
* Significant renal, cardiovascular, pulmonary, or neurological disease.
* Received solid organ or bone marrow transplantation.
* Is currently receiving therapy with immunomodulators (e.g., corticosteroids, etc.), investigational agents, nephrotoxic agents, or agents susceptible of modifying renal excretion.
* Has proximal tubulopathy.
* Use of other investigational drugs at the time of enrollment, or within 30 days
* History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes
* Is pregnant or breastfeeding.
* Is a women of child-bearing potential (WOCBP)unless post-menopausal or using one or more acceptable method of contraception.
* Patient has any other concurrent 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.
* Patient is currently abusing alcohol or illicit drugs, or has a history of alcohol abuse or illicit substance abuse within the preceding two years.
* Patient has a medical condition that requires prolonged or frequent use of systemic acyclovir or famciclovir.

Other protocol-defined inclusion/exclusion criteria may apply

Primary outcomes:
measure: Change in Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Level From Baseline to Week 12.
timeFrame: Baseline, Week 12
Secondary outcomes:
measure: Change in Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Level From Baseline to Weeks 2, 4 and 8.
timeFrame: Baseline, Week 2, Week 4, Week 8
measure: Percentage of Patients Who Are Polymerase Chain Reaction(PCR)Negative at Week 12
timeFrame: Week 12
measure: Percentage of Patients Who Achieve Hepatitis B "e" Antigen (HBeAg) Loss and HBeAg Seroconversion at Week 12
timeFrame: Week 12
measure: Characterization of Very Early Viral Kinetics Through Estimated Viral Load
timeFrame: Week 12
measure: Characterization of Very Early Viral Kinetics Through Viral Clearance
timeFrame: Week 12
measure: Characterization of Very Early Viral Kinetics Through Rate of Infected Cell Loss
timeFrame: Week 12
measure: Characterization of Very Early Viral Kinetics Through Efficiency Factor of Blocking Virus Production.
timeFrame: Week 12
measure: Characterization of Very Early Viral Kinetics Through Half-live of Free Virus
timeFrame: Week 12
Other outcomes:
Locations:
city: Hong Kong
country: China
facility: Department of Medicine, Queen Mary Hospital
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: