Entecavir Plus Adefovir in Lamivudine-Resistant Chronic Hepatitis B Patients Who Fail Lamivudine Plus Adefovir

NCT01023217 | Completed Phase 4 Results DMC

• 1 other identifier: AMC-2009-0536
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

The presence of persistent inadequate or suboptimal virologic response is a strong risk factor for viral resistance and breakthrough and also for disease progression of chronic hepatitis B, and thus, a change in therapy is required. The combination of entecavir (ETV) and adefovir (ADV) is a promising treatment for patients with lamivudine (LAM)-resistance who show suboptimal response to the combination of LAM and ADV. In this randomized, open labeled trial,the investigators will compare the efficacy of continuation of ADV plus LAM versus switch to ADV plus ETV in adults with LAM-resistant chronic hepatitis B who shows suboptimal response to the combination treatment of ADV and LAM.

Conditions

Hepatitis B, Chronic

Keywords

Chronic hepatitis B; lamivudine; adefovir; entecavir

Outcome Measures

Primary Outcomes (1)

• Complete Virologic Response (CVR, Serum HBV DNA Undetectable by PCR or Less Than 60 IU/mL)

  at week 52 from randomization

Secondary Outcomes (4)

• Reduction in Serum HBV DNA Levels

  at week 52 and at week 104 from randomization

• Genotypic Resistance to ADV or ETV

  at week 52 and at week 104 from randomization

• Normalization of ALT Level

  at week 52 and at week 104 from randomization

• Complete Virologic Response (CVR, Serum HBV DNA Undetectable by PCR or Less Than 60 IU/mL)

  at week 104 from randomization

Study Arms (2)

Adefovir plus Entecavir

EXPERIMENTAL

Adefovir + Entecavir for 104 weeks

Drug: Adefovir; Drug: Entecavir

Adefovir plus Lamivudine

ACTIVE COMPARATOR

Adefovir + Lamivudine for 52 weeks, and thereafter, Adefovir + Entecavir for 52 more weeks

Drug: Adefovir; Drug: Entecavir; Drug: Lamivudine

Interventions

Adefovir DRUG

Adefovir dipivoxil (Hepsera) 10 mg/day orally for 104 weeks

Also known as: Adefovir dipivoxil (Hepsera)

Adefovir plus Entecavir; Adefovir plus Lamivudine

Entecavir DRUG

Entecavir 1 mg/day orally

Also known as: Entecavir (Baraclude)

Adefovir plus Entecavir; Adefovir plus Lamivudine

Lamivudine DRUG

Lamivudine (Zeffix) 100 mg/day orally

Also known as: Lamivudine (Zeffix)

Adefovir plus Lamivudine

Eligibility Criteria

• Age: 16 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, 16 to 75 years of age
• Compensated liver disease(Child-Pugh class A)
• HBsAg positive at least 6 months or more
• HBeAg positive or negative
• Confirmation of Lamivudine-resistance HBV mutation anytime before the study
• Patients with suboptimal response (HBV DNA \> 2000 IU/mL despite combination of Adefovir \[10 mg/day\] plus Lamivudine \[100 mg/day\] for 6 months or more). Serum HBV DNA should be determined by the PCR assay at the local laboratory at screening for this study
• Patient is ambulatory.
• Patient is willing and able to comply with the study drug regimen and all other study requirements.
• The patient is willing and able to provide written informed consent to participate in the study.

You may not qualify if:

• Patient has a history of hepatocellular carcinoma (HCC) or findings suggestive of possible HCC, such as suspicious foci on imaging studies or elevated serum alpha fetoprotein (AFP) levels. In patients with such findings, HCC should be ruled-out prior to randomizing the patient for the present study.
• Patient previously received oral antiviral agent other than Lamivudine or Adefovir
• Patient has received interferon or other immunomodulatory treatment for HBV infection within 12 months before screening for this study.
• Patient has concomitant other chronic viral infection (HCV or HIV)
• Patient has evidence of renal insufficiency defined as serum creatinine \> 1.5 mg/dL
• Patient has medical condition that requires use of systemic prednisolone or other immunosuppressive agent (including chemotherapeutic agent)
• Patient is currently abusing alcohol or illicit drugs, or has a history of alcohol abuse or illicit substance abuse within the preceding two years.
• Patient is pregnant or breastfeeding or willing to be pregnant
• Patient has one or more additional known primary or secondary causes of liver disease, other than hepatitis B (e.g., alcoholism, autoimmune hepatitis, malignancy with hepatic involvement, hemochromatosis, alpha-1 antitrypsin deficiency, Wilson's Disease, other congenital or metabolic conditions affecting the liver, congestive heart failure or other severe cardiopulmonary disease, etc.).
• A history of treated malignancy (other than hepatocellular carcinoma) is allowable if the patient's malignancy has been in complete remission, off chemotherapy and without additional surgical intervention, during the preceding three years.
• Clinical signs of decompensated liver disease as indicated by any one of the following:
• serum bilirubin \> 3 mg/dL
• prothrombin time \> 6 seconds prolonged or INR \>1.6
• serum albumin \< 2.8 g/dL
• History of ascites, variceal hemorrhage, or hepatic encephalopathy

Sponsors & Collaborators

• Asan Medical Center: lead

Study Sites (1)

Asan Medical Center

Seoul, The Meteropolis of Seoul, 138-736, South Korea

Location

Related Publications (1)

• Lim YS, Lee JY, Lee D, Shim JH, Lee HC, Lee YS, Suh DJ. Randomized trial of the virologic response during up to two years of entecavir-adefovir combination therapy in multiple-drug-refractory chronic hepatitis B virus patients. Antimicrob Agents Chemother. 2013 Jul;57(7):3369-74. doi: 10.1128/AAC.00587-13. Epub 2013 May 6.

  PMID: 23650172 DERIVED

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

adefovir; adefovir dipivoxil; entecavir; Lamivudine

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)

Zalcitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Dideoxynucleosides

Results Point of Contact

• Title: Professor Young-Suk Lim
• Organization: Asan Medical Center

limys@amc.seoul.kr

+82-2-3010-5933

Study Officials

• Young-suk Lim, M.D.,Ph.D.

  Asan Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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: December 1, 2009
• First Posted: December 2, 2009
• Study Start: November 1, 2009
• Primary Completion: July 1, 2012
• Study Completion: September 1, 2012
• Last Updated: February 10, 2014
• Results First Posted: January 13, 2014

Record last verified: 2014-01

Locations

KR (1)