Antiviral Efficacy of Switching to ETV Plus TDF

NCT ID: NCT01597934

Last Updated: 2014-01-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE4

Total Enrollment

104 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-08-31

Study Completion Date

2014-05-31

Brief Summary

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Switching to Entecavir(ETV) plus Tenofovir Disoproxil Fumarate(TDF) combination will result in faster and greater antiviral activity and lower rates of resistance emergence over maintaining Lamivudine(LAM)/Telbivudine(LdT)+Adefovir(ADV) combination in partial responders to LAM/LdT+ADV rescue therapy.

Earlier switching to combination with the most potent regimen will be more effective to achieve virologic response(VR) and prevent further resistance emergence.

All subjects will orally take assigned drugs once daily for 48 weeks. All subjects will be assessed at baseline and every three months thereafter. Evaluations at each visit will include vital signs, physical examinations, laboratory tests, HBV DNA levels and adverse events. At baseline and every six months thereafter, serum will be assayed for HBV serology. Genotypic analysis will be performed at baseline and 48 weeks.

Detailed Description

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1. As TDF has not been approved yet in Korea, current KASL practice guideline generally recommends to add ADV in LAM-resistant or LdT-resistant patients.
2. However, several local literatures reported a substantial proportion of patients treated with LAM plus ADV combination therapy showed a persistently inadequate or partial virologic response('VR') and YMDDm still maintained in spite of under rescue combination therapy.
3. Due to the unavailability of TDF in Korea, ETV plus ADV combination has being considered a better salvage therapy with non-overlapping cross-resistance profiles in pts who fail to LAM plus ADV rescue therapy and local report demonstrated that the rate of VR was significantly higher with ETV+ADV switching group than LAM+ADV continuation group in partial responder to LAM plus ADV combination rescue therapy for LAM resistance.
4. Hence, more earlier combination therapy with the most potent Nucleoside and Nucleotide analogue would be a promising salvage treatment for previous NA treatment failures but comparative prospective trials are limited.
5. Therefore, this study will investigate the greater effectiveness and safety of switching to the most potent combination versus maintaining LAM(or LdT) plus ADV and also compare the rate of VR based on the HBV DNA cut-off level at switching - more than and less than 20,000 IU/mL.

All subjects will orally take assigned drugs once daily for 48 weeks. All subjects will be assessed at baseline and every three months thereafter. Evaluations at each visit will include vital signs, physical examinations, laboratory tests, HBV DNA levels and adverse events. At baseline and every six months thereafter, serum will be assayed for HBV serology. Genotypic analysis will be performed at baseline and 48 weeks.

Conditions

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Chronic Hepatitis B

Keywords

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Chronic hepatitis B Partial virologic response YMDD mutation

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Group A:

Maintaining LAM/LdT+ADV combination Lamivudine 100mg / Telbivudine 600mg +Adefovir 10mg

Group Type ACTIVE_COMPARATOR

Group A (Zeffix, Sebivo, Hepsera)

Intervention Type DRUG

Maintaining LAM/LdT+ADV combination Lamivudine 100mg / Telbivudine 600mg +Adefovir 10mg

Group B

Switching to ETV plus TDF combination Entecavir 1.0mg + Tenofovir 300mg

Group Type EXPERIMENTAL

Group B (Baraclude, Viread)

Intervention Type DRUG

Switching to ETV plus TDF combination Entecavir 1.0mg + Tenofovir 300mg

Interventions

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Group A (Zeffix, Sebivo, Hepsera)

Maintaining LAM/LdT+ADV combination Lamivudine 100mg / Telbivudine 600mg +Adefovir 10mg

Intervention Type DRUG

Group B (Baraclude, Viread)

Switching to ETV plus TDF combination Entecavir 1.0mg + Tenofovir 300mg

Intervention Type DRUG

Other Intervention Names

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Zeffix Sebivo Hepsera Baraclude Viread

Eligibility Criteria

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Inclusion Criteria

1. ≥ 20 years of age
2. History of HBsAg positive for more than 6 months
3. History of genotypic resistance to LAM or LdT (YMDDm)
4. Partial responder (HBV DNA ≥ 60 IU/mL) currently receiving antiviral combination rescue therapy for at least 24 weeks of treatment with LAM+ADV or LdT+ADV
5. Hepatitis B e Antigen(HBeAg)-positive and -negative
6. Compensated liver disease (Child-Pugh A)
7. Signed written informed consent after being instructed about the objective and procedure of the clinical study

Exclusion Criteria

1. History of genotypic resistance to ADV
2. Most previous treatment of other than LAM+ADV and LdT+ADV
3. Subjects with Alanine Aminotransferase(ALT) \> 10xUpper Limit of normal(ULN)
4. Co-infected with hepatitis C virus(HCV) or HIV
5. Pregnant or lactating woman
6. Subject who needs long-term administration of drugs including immunosuppressive agents, agents related to high risk in the hepatic/renal toxicity, agents influencing renal excretion
7. History of liver transplantation or planned for liver transplantation
8. Subject who was diagnosed malignant tumor and has been receiving chemotherapy
9. Subject who has HCC history or who shows potential hepatocellular carcinoma (HCC) finding such as suspicious region in the radiologic exam(abdominal US or CT) or serum Alpha Feto Protein(AFP) elevation
10. Renal Insufficiency (CLcr \< 50ml/min based on Cockcroft-Gault equation considering weight, ages and serum creatinine)
11. Subject who has a liver disease other than chronic hepatitis B (e.g. hemochromatosis, Wilson's disease, alcoholic liver disease, nonalcoholic fatty liver disease, alpha 1-antitrypsin deficiency etc.)
12. Subject who has a history of hypersensitivity to study drug or its ingredients
13. Subject who is involved in other clinical trial within 60 days prior to study entry
14. Subject who the investigator deems inappropriate to participate in this study
Minimum Eligible Age

20 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Bristol-Myers Squibb

INDUSTRY

Sponsor Role collaborator

Seoul St. Mary's Hospital

OTHER

Sponsor Role collaborator

The Catholic University of Korea

OTHER

Sponsor Role collaborator

Soonchunhyang University Hospital

OTHER

Sponsor Role collaborator

Pusan National University Hospital

OTHER

Sponsor Role collaborator

Kyungpook National University Hospital

OTHER

Sponsor Role collaborator

Hallym University Medical Center

OTHER

Sponsor Role collaborator

Chonbuk National University Hospital

OTHER

Sponsor Role collaborator

Yonsei University

OTHER

Sponsor Role lead

Responsible Party

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Sang Hoon Ahn

Associate Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Sang Hoon Ahn, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Yonsei University

References

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Woo HY, Park JY, Bae SH, Kim CW, Jang JY, Tak WY, Kim DJ, Kim IH, Heo J, Ahn SH. Entecavir+tenofovir vs. lamivudine/telbivudine+adefovir in chronic hepatitis B patients with prior suboptimal response. Clin Mol Hepatol. 2020 Jul;26(3):352-363. doi: 10.3350/cmh.2019.0044n. Epub 2020 May 28.

Reference Type DERIVED
PMID: 32460460 (View on PubMed)

Other Identifiers

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AI463-274

Identifier Type: -

Identifier Source: org_study_id