NCT01597934

Brief Summary

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.

Trial Health

35
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
104

participants targeted

Target at P50-P75 for phase_4

Timeline
Completed

Started Aug 2012

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 8, 2012

Completed
7 days until next milestone

First Posted

Study publicly available on registry

May 15, 2012

Completed
3 months until next milestone

Study Start

First participant enrolled

August 1, 2012

Completed
1.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2014

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2014

Completed
Last Updated

January 31, 2014

Status Verified

January 1, 2014

Enrollment Period

1.7 years

First QC Date

May 8, 2012

Last Update Submit

January 30, 2014

Conditions

Chronic Hepatitis B

Keywords

Chronic hepatitis BPartial virologic responseYMDD mutation

Outcome Measures

Primary Outcomes (1)

  • The proportion of subjects who achieve virologic response(HBV DNA < 60 IU/mL, approximately 300 copies/mL) by real-time PCR at Week 48

    To compare the proportion of subjects who achieve virologic response(HBV DNA \< 60 IU/mL, approximately 300 copies/mL) in switching group(Entecavir plus Tenofovir) with that in maintaining group(Lamivudine/Telbivudine plus Adefovir) by real-time Polymerase chain reaction(PCR) at Week 48

    at Week 48

Secondary Outcomes (4)

  • Virologic efficacy

    Week 12, 24, 36, and 48

  • serologic efficacy

    Week 12, 24, 36, and 48

  • biochemical efficacy

    Week 12, 24, 36, and 48

  • Safety issue

    Week 12, 24, 36, and 48

Study Arms (2)

Group A:

ACTIVE COMPARATOR

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

Drug: Group A (Zeffix, Sebivo, Hepsera)

Group B

EXPERIMENTAL

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

Drug: Group B (Baraclude, Viread)

Interventions

Group A (Zeffix, Sebivo, Hepsera)DRUG

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

Also known as: Zeffix, Sebivo, Hepsera
Group A:
Group B (Baraclude, Viread)DRUG

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

Also known as: Baraclude, Viread
Group B

Eligibility Criteria

Age20 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • ≥ 20 years of age
  • History of HBsAg positive for more than 6 months
  • History of genotypic resistance to LAM or LdT (YMDDm)
  • 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
  • Hepatitis B e Antigen(HBeAg)-positive and -negative
  • Compensated liver disease (Child-Pugh A)
  • Signed written informed consent after being instructed about the objective and procedure of the clinical study

You may not qualify if:

  • History of genotypic resistance to ADV
  • Most previous treatment of other than LAM+ADV and LdT+ADV
  • Subjects with Alanine Aminotransferase(ALT) \> 10xUpper Limit of normal(ULN)
  • Co-infected with hepatitis C virus(HCV) or HIV
  • Pregnant or lactating woman
  • 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
  • History of liver transplantation or planned for liver transplantation
  • Subject who was diagnosed malignant tumor and has been receiving chemotherapy
  • 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
  • Renal Insufficiency (CLcr \< 50ml/min based on Cockcroft-Gault equation considering weight, ages and serum creatinine)
  • 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.)
  • Subject who has a history of hypersensitivity to study drug or its ingredients
  • Subject who is involved in other clinical trial within 60 days prior to study entry
  • Subject who the investigator deems inappropriate to participate in this study

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Related Publications (1)

  • 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.

    PMID: 32460460DERIVED

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

LamivudineTelbivudineadefovir dipivoxilentecavirTenofovir

Condition Hierarchy (Ancestors)

Hepatitis BBlood-Borne InfectionsCommunicable DiseasesInfectionsHepadnaviridae InfectionsDNA Virus InfectionsVirus DiseasesHepatitis, Viral, HumanHepatitis, ChronicHepatitisLiver DiseasesDigestive System DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

ZalcitabineDeoxycytidineCytidinePyrimidine NucleosidesPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsDeoxyribonucleosidesNucleosidesNucleic Acids, Nucleotides, and NucleosidesDideoxynucleosidesThymidineOrganophosphonatesOrganophosphorus CompoundsOrganic ChemicalsAdeninePurinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-Ring

Study Officials

  • Sang Hoon Ahn, MD, PhD

    Yonsei University

    PRINCIPAL INVESTIGATOR

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

May 8, 2012

First Posted

May 15, 2012

Study Start

August 1, 2012

Primary Completion

May 1, 2014

Study Completion

May 1, 2014

Last Updated

January 31, 2014

Record last verified: 2014-01