Comparison of Telbivudine Plus Adefovir With Lamivudine Plus Adefovir for the Treatment of Lamivudine-resistant Chronic Hepatitis B at 52 Weeks: A Pilot Study (TeSLA)

This study is currently recruiting participants.
Verified March 2013 by Korea University
Sponsor:
Information provided by (Responsible Party):
Hyung Joon Yim, Korea University
ClinicalTrials.gov Identifier:
NCT01804387
First received: December 23, 2011
Last updated: March 3, 2013
Last verified: March 2013
  Purpose

Lamivudine had been widely used for treatment-naïve chronic hepatitis B patients. However, development of antiviral resistance has been known as the major drawback: Incidence of lamivudine resistance was reported to be approximately 70% after 5 years (Lok AS et al, 2003). For the treatment of lamivudine resistance, adefovir has been widely used (Lok AS and McMahon B, 2009). However, switching to adefovir monotherapy was also reported to be at high risk of resistance, 25% at year 2 (Yeon JE et al, 2006). Recently, adding adefovir on lamivudine was shown to be superior to switching to adefovir monotherapy by decreasing the adefovir resistance (Rapti I et al, 2007, Lampertico P et al, 2007). However, combination of adefovir and lamivudine does not increase antiviral activity compared with adefovir monotherapy in patients with lamivudine resistance (Peters MG et al, 2004). As many patients are still viremic with the treatment of lamivudine and adefovir over 1 year, the investigators need more potent combination of the drugs. Telbivudine is a new nucleoside analogue with potent antiviral activity. The previous phase III study has shown the superiority of telbivudine over lamivudine in HBeAg positive and negative subjects (Lai CL et al, 2007). Therefore, telbivudine plus adefovir may be a better treatment option than lamivudine plus adefovir for the lamivudine-resistant chronic hepatitis B patients. No study assessing the efficacy of telbivudine plus adefovir has been conducted for these patients. The aim of this study is to evaluate the safety and efficacy of telbivudine plus adefovir compared with lamivudine plus adefovir in lamivudine resistant chronic hepatitis B patients at the end of 1 year follow-up,


Condition Intervention Phase
Chronic Hepatitis B
Drug: telbivudine plus adefovir
Drug: lamivudine plus adefovir
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: Comparison of Telbivudine Plus Adefovir With Lamivudine Plus Adefovir for the Treatment of Lamivudine-resistant Chronic Hepatitis B at 52 Weeks: A Pilot Study

Resource links provided by NLM:


Further study details as provided by Korea University:

Primary Outcome Measures:
  • The mean reduction of serum HBV DNA from the baseline at week 52. [ Time Frame: up to the end of year 1 (52 weeks) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • HBV DNA undetectability(<20 IU/mL) [ Time Frame: up to the end of year 1 (52 weeks) ] [ Designated as safety issue: No ]
    At the end of year 1 in the two groups, HBV DNA undetectability by real time PCR will be assessed.

  • mean serum HBV DNA level [ Time Frame: up to the end of year 1 (52 weeks) ] [ Designated as safety issue: No ]
  • rate of ALT normalization [ Time Frame: up to the end of year 1 (52 weeks) ] [ Designated as safety issue: No ]
  • rates of HBeAg loss [ Time Frame: up to the end of year 1 (52 weeks) ] [ Designated as safety issue: No ]
  • rate of HBeAg seroconversion at week 52. [ Time Frame: up to the end of year 1 (52 weeks) ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Antiviral resistance rate [ Time Frame: up to the end of year 1 (52 weeks) ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 60
Study Start Date: May 2011
Estimated Study Completion Date: May 2014
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Telbivudine plus adefovir
study drugs
Drug: telbivudine plus adefovir
telbivudine 600 mg qd plus adefovir 10 mg qd
Other Names:
  • telbivudine (sevibo)
  • adefovir (hepsera)
Active Comparator: Lamivudine plus adefovir
standard drugs
Drug: lamivudine plus adefovir
lamivudine 100 mg qd plus adefovir 10mg qd
Other Names:
  • lamivudine (zeffix)
  • adefovir (hepsera)

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. HBeAg positive or negative chronic hepatitis B patients (positive HBsAg more than 6 months)
  2. Age ≥ 18 years old, and ≤70 years old
  3. Previous treatment with lamivudine more than 6 months
  4. Being on lamivudine at the time of screening
  5. Confirmed genotypic resistance to lamivudine by RFMP (rtM204V or I)
  6. Presence of virologic breakthrough ≥1 log increase of HBV DNA above na dir)
  7. HBV DNA ≥ 20,000 IU/mL
  8. Patient willing to give an informed consent (If patient is <20 years old, the parent or legal guardian also need to give an informed consent)

Exclusion Criteria:

  1. Out of inclusion criteria
  2. Presence of adefovir resistance (rtA181T or V, rtN236T) by RFMP assay
  3. Laboratory abnormalities as follows at screening: AFP>100 ng/mL, serum phosphorous level<2.4 mg/dL, serum creatinine level> 1.5 mg/dL or creatinine clearance < 50 mL/min
  4. Patient with a history of decompensated liver disease: Any patients with a history of ascites, hepatic encephalopathy, variceal bleeding, jaundice, or CTP>7 points should be excluded.
  5. History of treatment with nucleos(t)ide analogues other than lamivudine more than 4 weeks
  6. History of immune modulatory drugs (interferon, thymosin-alfa) within 24 weeks of screening
  7. Liver transplant patient
  8. Patient co-infected with HIV, HCV, or HDV
  9. Patient with metabolic or genetic liver disease that may affect serum ALT level
  10. Habitual alcohol consumption (>140 g/week for male, >70 g/week for female)
  11. Patient not able to stop drugs that may affect ALT or HBV DNA level during study periods (ie. Steroid, immune-suppressants, non-steroidal anti-inflammatory drugs, acetaminophen,)
  12. Pregnant or lactating woman
  13. Menstruating woman unwilling to use appropriate methods of contraception (ie. Condom, oral contraceptives, tubal ligation)
  14. Patient with hepatocellular carcinoma (treated or not treated)
  15. Patient with any untreated malignancy
  16. Patient with history of malignancy cured within 5 years of screening
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01804387

Contacts
Contact: Hyung Joon Yim, M.D 82-31-412-5583 gudwns21@medimail.co.kr

Locations
Korea, Republic of
Korea University Ansan Hospital Recruiting
Ansan, Gyeonggi-do, Korea, Republic of, 425-707
Contact: Hyung Joon Yim, M.D    82-31-412-5583    gudwns21@medimail.co.kr   
Sponsors and Collaborators
Korea University
Investigators
Principal Investigator: Hyung Joon Yim, M.D Korea University
  More Information

No publications provided

Responsible Party: Hyung Joon Yim, Associate professor, Korea University
ClinicalTrials.gov Identifier: NCT01804387     History of Changes
Other Study ID Numbers: TeSLA study
Study First Received: December 23, 2011
Last Updated: March 3, 2013
Health Authority: Korea: Food and Drug Administration

Keywords provided by Korea University:
Chronic Hepatitis B
Telbivudine
Adefovir
Lamivudine resistance

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis B
Hepatitis, Chronic
Hepatitis B, Chronic
Hepatitis, Viral, Human
Liver Diseases
Digestive System Diseases
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Adefovir
Adefovir dipivoxil
Lamivudine
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
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 April 20, 2014