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Trial record 116 of 348 for:    hepatitis b | Open Studies

Tenofovir Versus Tenofovir + Telbivudine for Chronic Hepatitis B (DUAL)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2016 by National University Health System, Singapore
Sponsor:
Collaborators:
National Medical Research Council (NMRC), Singapore
Singapore Clinical Research Institute
Information provided by (Responsible Party):
Seng Gee Lim, National University Health System, Singapore
ClinicalTrials.gov Identifier:
NCT02774837
First received: May 12, 2016
Last updated: May 16, 2016
Last verified: May 2016
  Purpose
Chronic Hepatitis B is the most common cause of chronic viral liver disease worldwide afflicting 350 million persons, leading to significant morbidity and mortality due to liver disease and HCC in 20-40% of infected persons. With the advent of nucleoside analogues, this rescued patients with significant risk of disease progression, but in most circumstances, therapy was needed long term as HBsAg seroclearance was an uncommon occurrence, and stopping therapy was associated with relapse of disease and hepatitis B flares. The use of pegylated interferons showed increased HBeAg seroconversion and HBsAg seroclearance rates compared to nucleoside analogues , however combination nucleos(t)ide analogue therapy has been quite disappointing. However a recent showed that the combination of telbivudine and tenofovir in a response guided therapy design, had a remarkable 6% HBsAg seroclearance at week 52 in patients. Such results require further confirmation. There is currently an unmet need for the large number of patients on long term nucleoside analogue therapy who have not achieved HBeAg seroconversion or HBsAg seroclearance. Such patients are seeking alternatives to long term therapy hence an exploration of other therapeutic strategies is attractive. An additional benefit of telbivudine has been the surprising improvement in renal function and this study seeks to examine whether this can improve the renal impairment that may be seen with tenofovir. Our study proposes to examine if the combination of tenofovir and telbivudine can improve endpoints. Patients fulfilling inclusion and exclusion criteria will be randomized to tenofovir or tenofovir and telbivudine (1:1 ratio). The primary endpoint will be a qHBsAg reduction of >1log at week 96, which may predict future HBsAg seroclearance, which is also a secondary endpoint. An additional primary endpoint is increase in eGFR in the combination arm compared to the monotherapy arm. The study aims to enroll 146 patients randomized 1:1 ratio (73:73) patients. Multivariate analysis will be performed of baseline and on-treatment factors that predict the primary outcome.

Condition Intervention Phase
Chronic Hepatitis B
Drug: Tenofovir disoproxil
Drug: Telbivudine
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Open Label Study of Nucleus(t)Ide Treated Patients Randomised to Tenofovir, or Tenofovir + Telbivudine

Resource links provided by NLM:


Further study details as provided by National University Health System, Singapore:

Primary Outcome Measures:
  • quantitative HBsAg (qHBsAg) reduction >1 log IU/ml [ Time Frame: Baseline to week 96 ] [ Designated as safety issue: No ]
    Proportion of patients who have a reduction of qHBsAg >1 log IU/ml from baseline to week 96, in experimental arm versus control arm


Secondary Outcome Measures:
  • HBsAg loss [ Time Frame: Baseline to week 96 ] [ Designated as safety issue: No ]
    Proportion of patients who achieve HBsAg loss at week 96 in experimental versus control arms

  • HBsAg seroconversion [ Time Frame: Baseline to week 96 ] [ Designated as safety issue: No ]
    Proportion of patients who achieve HBsAg seroconversion at week 96 in experimental versus control arms

  • HBeAg loss [ Time Frame: Baseline to week 96 ] [ Designated as safety issue: No ]
    Proportion of patients who achieve HBeAg loss at week 96 in experimental versus control arms

  • HBeAg seroconversion [ Time Frame: Baseline to week 96 ] [ Designated as safety issue: No ]
    Proportion of patients who achieve HBeAg seroconversion at week 96 in experimental versus control arms

  • quantitative HBsAg decline by >0.5 log10 IU/mL [ Time Frame: Baseline, week 24, 48 and 96 ] [ Designated as safety issue: No ]
    Proportion of patients who have a reduction of qHBsAg >0.5 log IU/ml from baseline to week 96, in experimental arm versus control arm

  • Alteration in eGFR [ Time Frame: Baseline to week 96 ] [ Designated as safety issue: Yes ]
    Proportion of patients who have an increase in eGFR from baseline to week 96, in experimental arm versus control arm


Estimated Enrollment: 146
Study Start Date: May 2016
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: June 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: combination
Tenofovir disoproxil oral tablets 300mg once daily for 96 weeks and Telbivudine 600mg oral tablets once daily for 96 weeks
Drug: Tenofovir disoproxil
Tenofovir disoproxil 300mg once daily for 96 weeks
Other Name: Viread
Drug: Telbivudine
Telbivudine oral tablets 600mg once daily for 96 weeks
Other Name: Sebivo
Active Comparator: mono therapy
Tenofovir disoproxil oral tablets 300mg once daily for 96 weeks
Drug: Tenofovir disoproxil
Tenofovir disoproxil 300mg once daily for 96 weeks
Other Name: Viread

Detailed Description:

Each subject must sign and date a study-specific informed consent form (ICF) prior to their participation in any screening activities. Prospective subjects should be screened no more than 28 days prior to administration of the first dose of study drug on Day 1. Screening evaluations will be used to determine eligibility of each candidate for study enrollment. Subjects meeting all of the inclusion criteria and none of the exclusion criteria as determined during screening will be eligible for the study. Candidates who fail to meet eligibility criteria by screening evaluations may be re-screened one time. Eligible patients at the end of screening will be randomised in a 1:1 ratio to experimental (combination) arm versus control (mono therapy) arm.

Randomisation will be performed by computer generated random codes (performed by Singapore Clinical Research Institute) with a masked allocation sequence. There will be no blinding of therapy and the study will be conducted as an open label study since the outcomes are objectively measurable.

After randomisation patients will be monitored 12 weekly for the first 24 weeks, then every 24 weekly until the last visit at 96 weeks.

At each visit, patients will have a clinical evaluation and have a panel of laboratory tests:

  • Hematology: Full blood count, prothrombin time and international normalized ratio
  • Chemistry: Sodium, potassium, creatinine, albumin, alkaline phosphatase, -aspartate transaminase, alanine transaminase, lactate dehydrogenase, total bilirubin, creatine phosphokinase, alphafetoprotein,
  • Urinalysis: Urine dipstick (Appearance, color, leucocytes, nitrite, urobilinogen, protein, PH, specific gravity, ketone, bilirubin and glucose).
  • Viral serology: HBeAg, anti-HBe, HBsAg, qHBsAg and anti-HBs
  Eligibility

Ages Eligible for Study:   21 Years to 65 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Presence of positive HBsAg or HBV DNA for at least 6 months.
  • Documented HBeAg positive or HBeAg negative.
  • On any NA (lamivudine, adefovir, entecavir, tenofovir or combination of any of these four) for ≥ 1 year
  • HBV DNA viral load ≤1.0 x 10^5 copies/ml at screening
  • ALT ≤ 1 x ULN (upper limit normal) U/L
  • A transient elastography (Fibroscan®) to evaluate the fibrosis stage will be performed at screening if it is not done in the past 6 months prior to screening. -Patient with compensated cirrhosis are permitted for this study.
  • eGFR ≥ 50 mL/min, as calculated by CKI-EPI equation.
  • Patient has agreed not to take any other investigational drug or systemic anti-viral, cytotoxic, corticosteroid, immunomodulatory agents or Chinese traditional remedies unless clinically indicated.
  • Patient is able to give written consent prior to study start and to comply with the study requirements.
  • Women of childbearing potential age must have a negative serum (ß-HCG) pregnancy test taken within 14 days of starting therapy
  • Lactating/breastfeeding female subjects must agree to discontinue nursing before initiation of study medication(s).

Exclusion Criteria:

  • Evidence of decompensated liver disease defined as direct (conjugated) bilirubin >1.2xULN, prothrombin time (PT) >1.5x upper limit of normal (ULN), serum albumin <35 g/L, or prior history of clinical hepatic decompensation (egs. ascites, encephalopathy, variceal hemorrhage).
  • Evidence of hepatocellular carcinoma (HCC).
  • Have any of the following laboratory tests within 4 weeks of study entry:

    • Active co-infection with HIV antibody or HCV antibody or HDV antibody positivity
    • Evidence of chronic renal insufficiency as defined by an eGFR (by CKD-EPI equation of < 50 mL/min).
  • Previous treatment with any form of interferon, Immunomodulators, systemic cytotoxic agents, or systemic corticosteroids within 6 months prior to screening.
  • Prolonged exposure to known hepatotoxins such as alcohol or drugs.
  • History of clinically relevant psychiatric disease, seizures, central nervous system dysfunction, severe pre-existing cardiac, renal, hematological disease or medical illness that in the investigator's opinion might interfere with therapy.
  • Current or known history of malignant disease within 5 years of trial entry.
  • Patients with a history of or currently known muscle related disease.
  • Liver or any other organ transplant other than cornea and hair.
  • Women who are pregnant and who are not practicing adequate birth control measures, or who are lactating.
  • Patients with specific contraindications to study drugs according to their Singapore Package Insert.
  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: NCT02774837

Contacts
Contact: Seng Gee Lim, MBBS, FRACP, FRCP, MD, FAMS +65-67724369 mdclimsg@nus.edu.sg
Contact: Clarissa Chia +65-67725715 mdccsyc@nus.edu.sg

Locations
Singapore
National University Hospital Recruiting
Singapore, Singapore, 119228
Contact: Gwendoline Tan, MBBS    +65-67727682    gwendoline_tan@nuhs.edu.sg   
Principal Investigator: Seng Gee Lim, MBBS, FRACP, FRCP, MD, FAMS         
Sub-Investigator: Yock Young Dan, MBBS, MRCP, M Med, FAMS         
Sub-Investigator: Kieron Lim, MBBS, FRCP, FAMS         
Sub-Investigator: Yin Mei Lee, MBBS, MRCP, SAB         
Sub-Investigator: Guan Huei Lee, MBBS, MRCP, FRCP, PhD         
Sub-Investigator: Poh Seng Tan, MBBS, MRCP, MMed, FAMS         
Sub-Investigator: Mark Muthiah, MBBS, MRCP, MMED         
Sub-Investigator: Chern Hao Chong, MBBS, MCRP, MMED         
Sub-Investigator: Wai Mun Loo, BM, MCRP         
Sub-Investigator: Dariusz Olyszyna, MD, PhD, FAMS, MMedSci.         
Sponsors and Collaborators
Seng Gee Lim
National Medical Research Council (NMRC), Singapore
Singapore Clinical Research Institute
Investigators
Principal Investigator: Seng Gee Lim, MBBS, FRACP, FRCP, MD, FAMS National University Health System
  More Information

Publications:

Responsible Party: Seng Gee Lim, Director of Hepatology, National University Health System, Singapore
ClinicalTrials.gov Identifier: NCT02774837     History of Changes
Other Study ID Numbers: 2013/00215 
Study First Received: May 12, 2016
Last Updated: May 16, 2016
Health Authority: Singapore: Health Sciences Authority
Individual Participant Data  
Plan to Share IPD: Undecided

Keywords provided by National University Health System, Singapore:
nucleoside analogues
tenofovir
telbivudine
quantitative HBsAg
combination therapy

Additional relevant MeSH terms:
Hepatitis
Hepatitis, Chronic
Hepatitis B
Hepatitis B, Chronic
Hepatitis, Viral, Human
Liver Diseases
Digestive System Diseases
Hepadnaviridae Infections
DNA Virus Infections
Virus Diseases
Tenofovir
Telbivudine
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-HIV Agents

ClinicalTrials.gov processed this record on December 09, 2016