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

NCT01594905 | Unknown Phase 4 DMC

• 1 other identifier: AI463-273
• Study Type: interventional
• Target: 90
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Chronic Hepatitis B

Keywords

To explore; adequate management; CHB; Multidrug resistance

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 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

  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

  Week 4, 12, 24, 36, and 48

Study Arms (1)

Entecavir 1.0mg + Tenofovir 300mg

EXPERIMENTAL

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

Drug: Entecavir + Tenofovir (MDR group)

Interventions

Entecavir + Tenofovir (MDR group) DRUG

Entecavir 1.0mg + Tenofovir 300mg

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

Entecavir 1.0mg + Tenofovir 300mg

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

• 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 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
• Renal Insufficiency (CLcr \< 50ml/min based on Cockcroft-Gault equation considering weight, ages and serum creatinine)
• 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.)
• 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

Sponsors & Collaborators

• Yonsei University: lead
• Bristol-Myers Squibb: collaborator
• Seoul St. Mary's Hospital: collaborator
• The Catholic University of Korea: collaborator

Related Publications (1)

• 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.

  PMID: 26781724 DERIVED

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

entecavir; Tenofovir

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)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Sang Hoon Ahn, MD, PhD

  Yonsei University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: May 7, 2012
• First Posted: May 9, 2012
• Study Start: August 1, 2012
• Primary Completion: April 1, 2014
• Study Completion: April 1, 2014
• Last Updated: January 31, 2014

Record last verified: 2014-01