Emtricitabine Plus Adefovir Dipivoxil for Naive Chinese HBV Related Cirrhosis Patients

This study evaluates generic emtricitabine(FTC) plus adefovir dipivoxil in Chinese naive HBV related cirrhosis patients. Patients were divided into 2 groups: compensated HBV related cirrhosis patients and decompensated HBV related cirrhosis patients.

Study Overview

• Status: Unknown
• Conditions: Fibrosis; Hepatitis B, Chronic
• Intervention / Treatment: Drug: Emtricitabine plus adefovir dipivoxil

Detailed Description

Generic emtricitabine(FTC) has been approved for treatment of naive chronic hepatitis B(CHB) patients in China. Yet data are limited for this agent plus adefovir dipivoxil in cirrhosis patients. The investigators design this trial to test the effect of FTC plus adefovir dipivoxil in Chinese naive compensated and decompensated HBV related cirrhosis patients.

• Study Type: Interventional
• Enrollment (Anticipated): 400
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Jun Cheng, M.D.; Phone Number: +86 10 84322116; Email: jun.cheng.ditan@gmail.com
• Study Contact Backup: Name: Song Yang, M.D.; Phone Number: +86 15011210692; Email: sduyangsong@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Dignosed cirrhosis patients
• HBsAg positive for more than 6 months
• HBV DNA detectable
• Nucleoside/nucleotide naive patients

Exclusion Criteria:

• Diagnosed HCC with AFP and ultrasound, CT or MRI
• Creatine >130μmol/L or Ccr < 70mL/min
• Hemoglobin <100g/L
• Coinfected with HAV,HEV,HCV,HDV or HIV
• ANA > 1:100
• Uncontrolled cardiovascular diseases, kidney diseases,lung diseases, neurological diseases, digestive diseases,metabolic disorders, immune-compromised diseases or cancer;
• Drug abuse or alcohol addiction
• Previous history of taking agents of lamivudine, adefovir, tenofovir entecavir or telbivudine
• Long-term use of immunosuppressor or immunomodulator 6 months before enrollment to this trial
• Underwent liver transplantation or liver transplantation in schedule
• Allergic to nucleoside or nucleotide analogues
• Pregnancy or in breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: compensated HBV related cirrhosis patients; Chinese naive compensated HBV related cirrhosis patients were treated with generic emtricitabine capsule(200 mg one time per day) plus adefovir dipivoxil(10 mg one time per day) for 96 weeks	Drug: Emtricitabine plus adefovir dipivoxil; emtricitabine plus adefovir dipivoxil were given to each patients for 96 weeks; Other Names: Brand name of emtricitabine：Huierding
Experimental: decompensated HBV related cirrhosis patients; Chinese naive decompensated HBV related cirrhosis patients were treated with generic emtricitabine capsule(200 mg one time per day) plus adefovir dipivoxil(10 mg one time per day) for 96 weeks	Drug: Emtricitabine plus adefovir dipivoxil; emtricitabine plus adefovir dipivoxil were given to each patients for 96 weeks; Other Names: Brand name of emtricitabine：Huierding

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
virological response rate	HBV DNA < 500 copies/ml	week 96

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HBV DNA decrease level	HBV DNA decrease compared with baseline（log10 copies/ml）	week24, 48, 72 and 96
HBV DNA negativity rate	HBV DNA < 500 copies/ml	week 24, 48 and 72
biochemical response	ALT normalization	week 24,48,72 and 96
HBeAg loss	HBeAg loss in HBeAg positive group	week 24,48,72 and 96
HBeAg seroconversion	HBeAg seroconversion in HBeAg positive group	week 24,48,72 and 96
HBeAg reversion	HBeAg positive in Baseline HBeAg negativie group patients	week 24,48,72 and 96
HBsAg loss	HBsAg loss in both group	week 24,48,72 and 96
HBsAg seroconversion	HBsAg loss and anti-HBs positive	week 24,48,72 and 96
HBV genetic resistance to emtricitabine and adefovir	HBV genetic resistance to emtricitabine and adefovir	week 24,48,72 and 96
adverse event	type and rate of adverse events;type and rate of severe adverse event	week 24,48,72 and 96
incidence of HCC	incidence of HCC in both groups	week 24,48,72 and 96
change of MELD score and Child-Pugh score	change of MELD score and Child-Pugh score in both groups	week 24,48,72 and 96

Collaborators and Investigators

• Sponsor: Asian-Pacific Alliance of Liver Disease, Beijing
• Collaborators: Beijing Ditan Hospital; National Health and Family Planning Commission, P.R.China; Hebei Medical University Pharmaceutical Factory
• Investigators: Principal Investigator: Jun Cheng, M.D., Asian Pacific Alliance of Liver Diseases, Beijing

Publications and helpful links

General Publications

• Lim SG, Ng TM, Kung N, Krastev Z, Volfova M, Husa P, Lee SS, Chan S, Shiffman ML, Washington MK, Rigney A, Anderson J, Mondou E, Snow A, Sorbel J, Guan R, Rousseau F; Emtricitabine FTCB-301 Study Group. A double-blind placebo-controlled study of emtricitabine in chronic hepatitis B. Arch Intern Med. 2006 Jan 9;166(1):49-56. doi: 10.1001/archinte.166.1.49.
• Gish RG, Leung NW, Wright TL, Trinh H, Lang W, Kessler HA, Fang L, Wang LH, Delehanty J, Rigney A, Mondou E, Snow A, Rousseau F. Dose range study of pharmacokinetics, safety, and preliminary antiviral activity of emtricitabine in adults with hepatitis B virus infection. Antimicrob Agents Chemother. 2002 Jun;46(6):1734-40. doi: 10.1128/AAC.46.6.1734-1740.2002.

Study record dates

Study Major Dates

• Study Start: January 1, 2015
• Primary Completion (Anticipated): July 1, 2015
• Study Completion (Anticipated): July 1, 2017

Study Registration Dates

• First Submitted: December 23, 2014
• First Submitted That Met QC Criteria: December 29, 2014
• First Posted (Estimate): December 30, 2014

Study Record Updates

• Last Update Posted (Estimate): December 30, 2014
• Last Update Submitted That Met QC Criteria: December 29, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Keywords: Cirrhosis; Hepatitis B virus; Emtricitabine; Adefovir dipivoxil
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Hepatitis, Chronic; Fibrosis; Hepatitis B; Hepatitis; Hepatitis B, Chronic; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Emtricitabine; Adefovir; Adefovir dipivoxil
• Other Study ID Numbers: FTC-01-cirrhosis patients