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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)

Primary Purpose

Chronic Hepatitis B

Status

Unknown status

Phase

Phase 4

Locations

Korea, Republic of

Study Type

Interventional

Intervention

telbivudine plus adefovir

lamivudine plus adefovir

About this trial

This is an interventional treatment trial for Chronic Hepatitis B focused on measuring Chronic Hepatitis B, Telbivudine, Adefovir, Lamivudine resistance

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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)

Exclusion Criteria:

Out of inclusion criteria
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

Sites / Locations

Korea University Ansan HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

Telbivudine plus adefovir

Lamivudine plus adefovir

Arm Description

study drugs

standard drugs

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

HBV DNA undetectability(<20 IU/mL)

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

rate of ALT normalization

rates of HBeAg loss

rate of HBeAg seroconversion at week 52.

Full Information

NCT ID

NCT01804387

First Posted

December 23, 2011

Last Updated

March 3, 2013

Sponsor

Korea University

1. Study Identification

Unique Protocol Identification Number

NCT01804387

Brief 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

Acronym

TeSLA

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2013

Overall Recruitment Status

Unknown status

Study Start Date

May 2011 (undefined)

Primary Completion Date

December 2013 (Anticipated)

Study Completion Date

May 2014 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Korea University

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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,

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chronic Hepatitis B

Keywords

Chronic Hepatitis B, Telbivudine, Adefovir, Lamivudine resistance

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Telbivudine plus adefovir

Arm Type

Active Comparator

Arm Description

study drugs

Arm Title

Lamivudine plus adefovir

Arm Type

Active Comparator

Arm Description

standard drugs

Intervention Type

Drug

Intervention Name(s)

telbivudine plus adefovir

Other Intervention Name(s)

telbivudine (sevibo), adefovir (hepsera)

Intervention Description

telbivudine 600 mg qd plus adefovir 10 mg qd

Intervention Type

Drug

Intervention Name(s)

lamivudine plus adefovir

Other Intervention Name(s)

lamivudine (zeffix), adefovir (hepsera)

Intervention Description

lamivudine 100 mg qd plus adefovir 10mg qd

Primary Outcome Measure Information:

Title

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

Time Frame

up to the end of year 1 (52 weeks)

Secondary Outcome Measure Information:

Title

HBV DNA undetectability(<20 IU/mL)

Description

At the end of year 1 in the two groups, HBV DNA undetectability by real time PCR will be assessed.

Time Frame

up to the end of year 1 (52 weeks)

Title

mean serum HBV DNA level

Time Frame

up to the end of year 1 (52 weeks)

Title

rate of ALT normalization

Time Frame

up to the end of year 1 (52 weeks)

Title

rates of HBeAg loss

Time Frame

up to the end of year 1 (52 weeks)

Title

rate of HBeAg seroconversion at week 52.

Time Frame

up to the end of year 1 (52 weeks)

Other Pre-specified Outcome Measures:

Title

Antiviral resistance rate

Time Frame

up to the end of year 1 (52 weeks)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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) Exclusion Criteria: Out of inclusion criteria 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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Hyung Joon Yim, M.D

Phone

82-31-412-5583

gudwns21@medimail.co.kr

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Hyung Joon Yim, M.D

Organizational Affiliation

Korea University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Korea University Ansan Hospital

City

Ansan

State/Province

Gyeonggi-do

ZIP/Postal Code

425-707

Country

Korea, Republic of

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Hyung Joon Yim, M.D

Phone

82-31-412-5583

gudwns21@medimail.co.kr

12. IPD Sharing Statement

Learn more about this trial

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

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