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Status unknownNCT01594905Updated Jan 31, 2014

Entecavir Plus Tenofovir Combination in Subjects With Multi-drug Resistant Chronic Hepatitis B Virus Infection

A Phase 4 interventional study of Entecavir + Tenofovir (MDR group) in Chronic Hepatitis B, sponsored by Yonsei University. Status unknown. Open to participants aged 20 Years and older. Per ClinicalTrials.gov, last updated 2014-01-31.

Sponsored by Yonsei University · Phase 4, Interventional, and Treatment

The sponsor has not verified this record recently (last verified Jan 2014), so the status shown — last known as Active, not recruiting — may be out of date.
Phase
Phase 4
Study type
Interventional
Enrollment
90
Allocation
Not applicable
Ages
20 Years and older
Sex
All
01

Study summary

Entecavir(ETV) plus Tenofovir Disoproxil Fumarate(TDF) combination will show effective antiviral activity and prevent further development of antiviral resistance in hepatitis B e antigen(HBeAg)-positive or -negative Chronic Hepatitis B(CHB) patients who experienced multidrug resistance

All subjects will orally take investigational drugs once daily for 48 weeks. All subjects will be assessed at baseline, Week 4, 12, 24, 36 and 48. Evaluations at each visit will include vital signs, physical examinations, laboratory tests and HBV DNA levels. They were also questioned about adverse events and concomitant medications. At baseline and every six months thereafter, serum will be assayed for HBV serology. Genotypic analysis will be performed at baseline and 48 weeks.

Read the detailed description
  1. It has been one of unsolved issues and unmet needs in CHB management to develop an optimal combination regimen to manage multidrug resistant HBV characterized by selection of variants with two or more classes A of signature genotypic resistant mutations1-3
  2. Currently adding on Adefovir(ADV) has been generally recommended in Lamivudine(LAM)- or Telbivudine(LdT)-resistant patients but little is known about the optimal management of CHB patients who developed multidrug resistance4
  3. Recent report has shown that the combination of LAM plus ADV did not suppress HBV DNA effectively in CHB patients with resistance mutations to both drugs. Only 12.2% of these pts achieved virologic response(VR; HBV DNA \<60 IU/mL) at 12 months and multivariable analysis showed that LAM+ADV group and the presence of the rtA181V/T mutation were independently associated with a decreased rate of virologic response (HBV DNA \<2,000 IU/ml) at 12 months4
  4. ETV has been demonstrated to be effective in patients with ADV resistance but not in patients with proven YMDD mutation. In contrast, TDF has been shown to be effective in patients with YMDD mutation but not necessarily in all patients with ADV resistance.1-3
  5. Thus theoretically, the combination of the most potent nucleoside analogue and nucleotide analogue with non-overlapping resistance profiles, such as ETV plus TDF, is expected to be a promising salvage treatment for multidrug resistant HBV but clinical evidence is limited
  6. Therefore, this study will explore that adequate management of multidrug resistant patients using ETV plus TDF combination may lead to faster and greater viral suppression and prevent further emergence of antiviral resistance

All subjects will orally take investigational drugs once daily for 48 weeks. All subjects will be assessed at baseline, Week 4, 12, 24, 36 and 48. Evaluations at each visit will include vital signs, physical examinations, laboratory tests and HBV DNA levels. They were also questioned about adverse events and concomitant medications. At baseline and every six months thereafter, serum will be assayed for HBV serology. Genotypic analysis will be performed at baseline and 48 weeks.

02

Conditions studied

  • Chronic Hepatitis B

Keywords

  • To explore
  • adequate management
  • CHB
  • Multidrug resistance
03

In context

Hepatitis A

2,709 studies on the registry are indexed under Hepatitis A; 142 are open to participants now.

This study's planned enrollment of 90 is close to the median of 100 across 1,886 interventional studies indexed under Hepatitis A.

Browse Hepatitis A studies →

Lead sponsor

Yonsei University is the lead sponsor of 1,387 studies on the registry; 232 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
20 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. ≥ 20 years of age
  2. History of HBsAg positive for more than 6 months
  3. Subject who has a history of genotypic resistance to NAs from two different classes A
  4. Detectable HBV DNA (≥ 60 IU/mL) while on any rescue treatment regimen for at least 24 weeks
  5. 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

Exclusion Criteria:

  1. Subjects with Alanine Aminotransferase(ALT) > 10xUpper Limit of normal(ULN)
  2. Co-infected with hepatitis C virus(HCV) or HIV
  3. Pregnant or lactating woman
  4. 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
  5. History of liver transplantation or planned for liver transplantation
  6. Subject who was diagnosed malignant tumor and has been receiving chemotherapy
  7. Subject who has hepatocellular carcinoma(HCC) history or who shows potential HCC finding such as suspicious region in the radiologic exam(abdominal US or CT) or serum Alpha Feto Protein(AFP) elevation
  8. Renal Insufficiency (CLcr \< 50ml/min based on Cockcroft-Gault equation considering weight, ages and serum creatinine)
  9. Patient 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.)
  10. Subject who has a history of hypersensitivity to study drug or its ingredients
  11. Subject who is involved in other clinical trial within 60 days prior to study entry
  12. Subject who the investigator deems inappropriate to participate in this study
05

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
90 participants (estimated)

Study arms

  • Experimental
    Entecavir 1.0mg + Tenofovir 300mg

    All subjects will orally take investigational drugs once daily for 48 weeks.

    Drug: Entecavir + Tenofovir (MDR group)

Interventions

  • DrugEntecavir + Tenofovir (MDR group)

    Entecavir 1.0mg + Tenofovir 300mg

    Also known as: Entecavir 1.0mg - Braclude, Tenofovir 300mg - Viread

06

What researchers measure

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 evaluate the proportion of subjects who achieve virologic response(HBV DNA \< 60 IU/mL, approximately 300 copies/mL) by real-time Polymerase chain reaction(PCR) at Week 48 after Entecavir plus Tenofovir combination therapy

    Time frame: at Week 48

Secondary outcomes

  1. Virologic, serologic, biochemical efficacy and safety profile, as measured by the incidence of clinical adverse events and laboratory abnormalities including renal marker

    To evaluate virologic, serologic and biochemical response and safety of Entecavir plus Tenofovir combination therapy for 48 weeks

    Time frame: Week 4, 12, 24, 36, and 48

07

Study locations

No study locations are listed for this record.

08

References and documents

Publications

  • Park JY, Kim CW, Bae SH, Jung KS, Kim HY, Yoon SK, Han KH, Ahn SH. Entecavir plus tenofovir combination therapy in patients with multidrug-resistant chronic hepatitis B: results of a multicentre, prospective study. Liver Int. 2016 Aug;36(8):1108-15. doi: 10.1111/liv.13059. Epub 2016 Feb 7. PubMed 26781724 ↗
09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jan 31, 2014, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT01594905
Lead sponsor
Yonsei University
Collaborators
Bristol-Myers Squibb, Seoul St. Mary's Hospital, The Catholic University of Korea
Responsible party
Sang Hoon Ahn (Associate Professor, Yonsei University) — Principal investigator
First posted
May 9, 2012
Start date
Aug 2012
Primary completion
Apr 2014 (estimated)
Completion
Apr 2014 (estimated)
Last update
Jan 31, 2014

Study contacts

Sang Hoon Ahn, MD, PhD
principal investigator · Yonsei University

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is status unknown, as verified in Jan 2014. You cannot join it, but the record below documents what was studied.

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