Effects of Telbivudine and Tenofovir Disoproxil Fumarate Treatment on the Hepatitis B Virus DNA Kinetics in CHB

NCT00805675 | Completed Phase 3 Results

• 1 other identifier: CLDT600AHK01
• Study Type: interventional
• Target: 83
• Locations: 1 country
• Sites: 1

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.

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)

Outcome Measures

Primary Outcomes (1)

• Change in Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Level From Baseline to Week 12.

  Baseline HBV DNA is defined as the last pre-dose assessment of HBV DNA. Serum HBV DNA determinations were performed at a central laboratory through use of the COBAS TaqMan™ HBV DNA assay (Roche Molecular Systems, Pleasanton, CA, USA) which utilized the Real-time polymerase chain reaction (PCR) method and automated extraction by Cobas Ampliprep (threshold for detection 12 IU/mL). The Screening serum HBV DNA values must be ≥ 7 log10 copies/mL by COBAS TaqMan™ HBV DNA assay.

  Baseline, Week 12

Secondary Outcomes (8)

• Change in Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Level From Baseline to Weeks 2, 4 and 8.

  Baseline, Week 2, Week 4, Week 8

• Percentage of Patients Who Are Polymerase Chain Reaction(PCR)Negative at Week 12

  Week 12

• Percentage of Patients Who Achieve Hepatitis B "e" Antigen (HBeAg) Loss and HBeAg Seroconversion at Week 12

  Week 12

• Characterization of Very Early Viral Kinetics Through Estimated Viral Load

  Week 12

• Characterization of Very Early Viral Kinetics Through Viral Clearance

  Week 12

Study Arms (3)

Telbivudine 600 mg monotherapy

EXPERIMENTAL

All patients in this arm were randomized to receive Telbivudine (LDT) 600 mg QD. Patients were randomized prior to the first dose of study medication, which was defined as the study Baseline (Day 1) Visit. Subsequently, patients returned to the clinic at Days 2, 4, 6, 8, 11, 15 (Wk 2), 22 (Wk 3), 29 (Wk 4), 43 (Wk 6), 57 (Wk 8), and 85 (Wk 12) during the 12 weeks treatment phase.

Drug: Telbivudine

Tenofovir disproxil fumarate 300 mg monotherapy

ACTIVE COMPARATOR

All patients in this arm were randomized to receive Tenofovir disoproxil fumarate 300 mg(equivalent to tenofovir disoproxil 245 mg)QD. Patients were randomized prior to the first dose of study medication, which was defined as the study Baseline (Day 1) Visit. Subsequently, patients returned to the clinic at Days 2, 4, 6, 8, 11, 15 (Wk 2), 22 (Wk 3), 29 (Wk 4), 43 (Wk 6), 57 (Wk 8), and 85 (Wk 12) during the 12 weeks treatment phase.

Drug: Tenofovir

Telbivudine 600 mg and Tenofovir 300 mg

ACTIVE COMPARATOR

All patients in this arm were randomized to receive Telbivudine (LDT) 600 mg QD and Tenofovir (TDF) 300 mg (equivalent to Tenofovir disoproxil 245 mg)QD. Patients were randomized prior to the first dose of study medication, which was defined as the study Baseline (Day 1) Visit. Subsequently, patients returned to the clinic at Days 2, 4, 6, 8, 11, 15 (Wk 2), 22 (Wk 3), 29 (Wk 4), 43 (Wk 6), 57 (Wk 8), and 85 (Wk 12) during the 12 weeks treatment phase.

Drug: Telbivudine plus tenofovir

Interventions

Telbivudine DRUG

600 mg monotherapy supplied in film-coated tablets.

Telbivudine 600 mg monotherapy

Tenofovir DRUG

Tenofovir disoproxil fumarate was supplied in 300 mg tablets

Tenofovir disproxil fumarate 300 mg monotherapy

Telbivudine plus tenofovir DRUG

Telbivudine 600 mg and Tenofovir 300 mg were purchased in commercial packs. Patients were instructed to take medication(s) orally every morning either with or without food.

Telbivudine 600 mg and Tenofovir 300 mg

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (1)

Department of Medicine, Queen Mary Hospital

Hong Kong, China

Location

MeSH Terms

Conditions

Hepatitis B

Interventions

Telbivudine; Tenofovir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Thymidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 9, 2008
• First Posted: December 10, 2008
• Study Start: November 1, 2008
• Primary Completion: December 1, 2010
• Last Updated: February 28, 2012
• Results First Posted: February 28, 2012

Record last verified: 2012-01

Locations

CN (1)