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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00805675
First received: December 9, 2008
Last updated: January 26, 2012
Last verified: January 2012
  Purpose

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.


Condition Intervention Phase
Hepatitis B Virus
Drug: Telbivudine
Drug: Tenofovir
Drug: Telbivudine plus tenofovir
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Change in Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Level From Baseline to Week 12. [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Change in Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Level From Baseline to Weeks 2, 4 and 8. [ Time Frame: Baseline, Week 2, Week 4, Week 8 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Patients Who Are Polymerase Chain Reaction(PCR)Negative at Week 12 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    Polymerase Chain Reaction (PCR) Negative is defined as HBV DNA levels <25 copies/ml.

  • Percentage of Patients Who Achieve Hepatitis B "e" Antigen (HBeAg) Loss and HBeAg Seroconversion at Week 12 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    HBeAg loss is defined as the loss of detectable serum HBeAg in a patient who was HBeAg positive at baseline. HBeAg seroconversion is defined as HBeAg loss with detectable Hepatitis B 'e' antibody (HBeAb). HBeAg stands for hepatitis B "e" antigen. This antigen is a protein from the hepatitis B virus that circulates in infected blood when the virus is actively replicating. The presence of HBeAg suggests that the person is infectious and is able to spread the virus to other people.

  • Characterization of Very Early Viral Kinetics Through Estimated Viral Load [ Time Frame: Week 12 ] [ Designated as safety issue: No ]

    The underlying bi‐phasic model of viral kinetics can be described as follows:

    V(t) (1 )pI(t) cV(t)I(t) (1 ) (T I(t))V(t) I(t)where V denotes serum viral load, I productively infected cells, ε the efficiency factor of blocking virus production, p the viral production rate, c the viral clearance rate, η the efficiency factor of blocking de novo infection, β the de novo infection rate, Tg comprise all infected and uninfected target cells, and δ the rate of infected cell loss


  • Characterization of Very Early Viral Kinetics Through Viral Clearance [ Time Frame: Week 12 ] [ Designated as safety issue: No ]

    The underlying bi‐phasic model of viral kinetics can be described as follows:

    V(t) (1 )pI(t) cV(t)I(t) (1 ) (T I(t))V(t) I(t)where V denotes serum viral load, I productively infected cells, ε the efficiency factor of blocking virus production, p the viral production rate, c the viral clearance rate, η the efficiency factor of blocking de novo infection, β the de novo infection rate, Tg comprise all infected and uninfected target cells, and δ the rate of infected cell loss


  • Characterization of Very Early Viral Kinetics Through Rate of Infected Cell Loss [ Time Frame: Week 12 ] [ Designated as safety issue: No ]

    The underlying bi‐phasic model of viral kinetics can be described as follows:

    V(t) (1 )pI(t) cV(t)I(t) (1 ) (T I(t))V(t) I(t)where V denotes serum viral load, I productively infected cells, ε the efficiency factor of blocking virus production, p the viral production rate, c the viral clearance rate, η the efficiency factor of blocking de novo infection, β the de novo infection rate, Tg comprise all infected and uninfected target cells, and δ the rate of infected cell loss


  • Characterization of Very Early Viral Kinetics Through Efficiency Factor of Blocking Virus Production. [ Time Frame: Week 12 ] [ Designated as safety issue: No ]

    The underlying bi‐phasic model of viral kinetics can be described as follows:

    V(t) (1 )pI(t) cV(t) I(t) (1 ) (T I(t))V(t) I(t) where V denotes serum viral load, I productively infected cells, ε the efficiency factor of blocking virus production, p the viral production rate, c the viral clearance rate, η the efficiency factor of blocking de novo infection, β the de novo infection rate, Tg comprise allinfected and uninfected target cells, and δ the rate of infected cell loss


  • Characterization of Very Early Viral Kinetics Through Half-live of Free Virus [ Time Frame: Week 12 ] [ Designated as safety issue: No ]

    The underlying bi‐phasic model of viral kinetics can be described as follows:

    V(t) (1 )pI(t) cV(t)I(t) (1 ) (T I(t))V(t) I(t)where V denotes serum viral load, I productively infected cells, ε the efficiency factor of blocking virus production, p the viral production rate, c the viral clearance rate, η the efficiency factor of blocking de novo infection, β the de novo infection rate, Tg comprise all infected and uninfected target cells, and δ the rate of infected cell loss



Enrollment: 83
Study Start Date: November 2008
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Telbivudine 600 mg monotherapy
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
600 mg monotherapy supplied in film-coated tablets.
Active Comparator: Tenofovir disproxil fumarate 300 mg monotherapy
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
Tenofovir disoproxil fumarate was supplied in 300 mg tablets
Active Comparator: Telbivudine 600 mg and Tenofovir 300 mg
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
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.

  Eligibility

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00805675

Locations
China
Department of Medicine, Queen Mary Hospital
Hong Kong, China
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00805675     History of Changes
Other Study ID Numbers: CLDT600AHK01
Study First Received: December 9, 2008
Results First Received: December 12, 2011
Last Updated: January 26, 2012
Health Authority: Hong Kong: Department of Health

Keywords provided by Novartis:
Chronic HBV
Asian adult subjects with chronic HBV, in immune tolerant phase, and positive for hepatitis B e antigen (HBeAg)

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis B
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Tenofovir
Tenofovir disoproxil
Telbivudine
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on September 16, 2014