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

NCT01804387 | Unknown Phase 4 DMC

• 1 other identifier: TeSLA study
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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,

Conditions

Chronic Hepatitis B

Keywords

Chronic Hepatitis B; Telbivudine; Adefovir; Lamivudine resistance

Outcome Measures

Primary Outcomes (1)

• The mean reduction of serum HBV DNA from the baseline at week 52.

  up to the end of year 1 (52 weeks)

Secondary Outcomes (5)

• HBV DNA undetectability(<20 IU/mL)

  up to the end of year 1 (52 weeks)

• mean serum HBV DNA level

  up to the end of year 1 (52 weeks)

• rate of ALT normalization

  up to the end of year 1 (52 weeks)

• rates of HBeAg loss

  up to the end of year 1 (52 weeks)

• rate of HBeAg seroconversion at week 52.

  up to the end of year 1 (52 weeks)

Other Outcomes (1)

• Antiviral resistance rate

  up to the end of year 1 (52 weeks)

Study Arms (2)

Telbivudine plus adefovir

ACTIVE COMPARATOR

study drugs

Drug: telbivudine plus adefovir

Lamivudine plus adefovir

ACTIVE COMPARATOR

standard drugs

Drug: lamivudine plus adefovir

Interventions

telbivudine plus adefovir DRUG

telbivudine 600 mg qd plus adefovir 10 mg qd

Also known as: telbivudine (sevibo), adefovir (hepsera)

Telbivudine plus adefovir

lamivudine plus adefovir DRUG

lamivudine 100 mg qd plus adefovir 10mg qd

Also known as: lamivudine (zeffix), adefovir (hepsera)

Lamivudine plus adefovir

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• HBeAg positive or negative chronic hepatitis B patients (positive HBsAg more than 6 months)
• Age ≥ 18 years old, and ≤70 years old
• Previous treatment with lamivudine more than 6 months
• Being on lamivudine at the time of screening
• Confirmed genotypic resistance to lamivudine by RFMP (rtM204V or I)
• Presence of virologic breakthrough ≥1 log increase of HBV DNA above na dir)
• HBV DNA ≥ 20,000 IU/mL
• 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)

You may not qualify if:

• Presence of adefovir resistance (rtA181T or V, rtN236T) by RFMP assay
• 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
• 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.
• History of treatment with nucleos(t)ide analogues other than lamivudine more than 4 weeks
• History of immune modulatory drugs (interferon, thymosin-alfa) within 24 weeks of screening
• Liver transplant patient
• Patient co-infected with HIV, HCV, or HDV
• Patient with metabolic or genetic liver disease that may affect serum ALT level
• Habitual alcohol consumption (\>140 g/week for male, \>70 g/week for female)
• 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,)
• Pregnant or lactating woman
• Menstruating woman unwilling to use appropriate methods of contraception (ie. Condom, oral contraceptives, tubal ligation)
• Patient with hepatocellular carcinoma (treated or not treated)
• Patient with any untreated malignancy
• Patient with history of malignancy cured within 5 years of screening

Sponsors & Collaborators

• Korea University: lead

Study Sites (1)

Korea University Ansan Hospital

Ansan, Gyeonggi-do, 425-707, South Korea

RECRUITING

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

Telbivudine; adefovir; adefovir dipivoxil; Lamivudine

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thymidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Zalcitabine; Deoxycytidine; Cytidine; Dideoxynucleosides

Study Officials

• Hyung Joon Yim, M.D

  Korea University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hyung Joon Yim, M.D

CONTACT

82-31-412-5583; gudwns21@medimail.co.kr

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate professor

Study Record Dates

• First Submitted: December 23, 2011
• First Posted: March 5, 2013
• Study Start: May 1, 2011
• Primary Completion: December 1, 2013
• Study Completion: May 1, 2014
• Last Updated: March 5, 2013

Record last verified: 2013-03

Locations

KR (1)