An Open Label, Multi Centre Phase IV Study of Adefovir Dipivoxil in Korean Patients With Chronic Hepatitis B (CHB)

NCT01205165 | Completed Phase 4 Results

• 1 other identifier: 103814
• Study Type: interventional
• Target: 104
• Locations: 0 countries
• Sites: N/A

Brief Summary

Objective(s) The primary study objective is to assess the antiviral effect of 12 weeks of adefovir dipivoxil treatment in Korean patients with chronic hepatitis B and compensated liver disease. The secondary study objectives are to assess the antiviral effect, clinical benefit and safety of 52 weeks of adefovir dipivoxil treatment. Endpoint(s) The primary efficacy endpoint is "Mean log10 reduction in serum HBV DNA level from baseline to Week 12". The secondary efficacy endpoints include (a) the proportion of patients achieving serum ALT normalization at Week 52, (b) other assessments of antiviral effects (the proportion of patients achieving HBV DNA no less than 300 copies per mL at Week 52), (c)HBeAg loss, HBeAg seroconversion, HBsAg loss and HBsAg seroconversion, (d)the proportion of patients achieving serum ALT normalization at Week 12. Study Design This is an open label, multi centre phase IV study for Korean patients with chronic hepatitis B and compensated liver disease, assessing the antiviral effect of 12 weeks treatment of Adefovir dipivoxil as a primary objective and antiviral effect, clinical benefit and safety of 52 weeks treatment as secondary objectives. Patients will be screened for eligibility criteria and the baseline visit for the treatment initiation should occur no more than 4 weeks after screening. Total treatment period will be 52 weeks and patients will return to the clinic for assessments as scheduled during treatment period. After the 52 week study period, it is likely that the patient will benefit from continued treatment with commercial adefovir. If in the investigator's clinical judgement this is the case, the investigator should ensure that a routine prescription is available in a timely manner, and that no unnecessary interruption in treatment occurs. Study Population A minimum of 100 male or female Korean patients more than 18 years of age with HBeAg positive chronic hepatitis B and compensated liver disease who meet the eligibility criteria will be enrolled. Study Assessments and Procedures Potential patients will be screened prior to study entry and eligible patients who have given their consent will have further baseline assessments. Following the screening, the first doses of study medications will be given at baseline and patients will return to the clinic for assessment as scheduled during treatment period. Patients who discontinue treatment prematurely will be followed up every 4 weeks for 12 weeks following the withdrawal visit. The following key assessment and or measurement will be made at one or more visits during the study. (See section 14.1 Appendix 1. Time and event schedule):

• Pregnancy test (females of child-bearing potential only)
• Haematology and serum chemistry profile including prothrombin time(PT) and AFP
• HBV DNA (Roche COBAS AMPLICOR HBV MONITOR Test, LLOD 300 copies per ml)
• Hepatitis B markers: HBeAg(Anti HBe will be tested if HBeAg is negative), HBsAg(Anti HBs will be tested if HBsAg is negative) Investigational Product(s) Adefovir dipivoxil 10mg tablets will be supplied by GlaxoSmithKline and presented as a white to off white, round tablets, packaged in the bottle containing 30 tablets

Conditions

Hepatitis B, Chronic

Outcome Measures

Primary Outcomes (1)

• Mean Log 10 Reduction in Serum Hepatitis B Virus (HBV), Deoxyribonucleic Acid (DNA) Level From Baseline to Week 12

  HBV DNA was tested with Roche Cobas Amplicor HBV monitor test, where the lower limit of detection was 300 copies/milliliter (mL), at baseline and other study visits. The mean log 10 reduction in serum HBV DNA level from baseline to week 12 was calculated as the week 12 value minus the baseline value. Baseline was the Day 1 for the study, when participant received study drug. Log 10 reduction implied reduced viral load.

  Baseline (Day 1) and Week 12

Secondary Outcomes (9)

• Number of Participants Achieving Alanine Aminotransferase (ALT) Normalization at Week 52

  At week 52

• Number of Participants Achieving Virological Response at Week 52

  At Week 52

• HBV DNA Levels at Each Collection Timepoint Through Week 52

  Week 4, week 8, week 12, week 20, week 28, week 36, week 44 and week 52

• Number of Participants With Hepatitis B e Viral Protein (HBeAg) Loss, HBeAg Seroconversion, Hepatitis B Virus Surface Antigen (HBsAg) Loss and HBsAg Seroconversion at Week 52

  Week 52

• Number of Participants Achieving ALT Normalization at Week 12

  at Week 12

Study Arms (1)

Adefovir Dipivoxil 10mg

EXPERIMENTAL

All enrolled subject were enrolled to adefovir dipivoxil 10mg arm.

Drug: Adefor dipivoxil

Interventions

Adefor dipivoxil DRUG

All enrolled subjects were enrolled to adefovir dipivoxil arm.

Adefovir Dipivoxil 10mg

Eligibility Criteria

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

You may qualify if:

• Age more than 18 years
• HBV Serology Presence of HBsAg for at least 6 months Presence of HBeAg at the time of screening Positive HBV DNA plasma assay with screening value at the time of screening
• \. Evidence of at least one elevated serum alanine amonotransferase (ALT) levels greater than 2 times (inclusive) the upper limit of the normal range (ULN) in the previous 6 months.
• serum ALT levels greater than 2 times (inclusive) the ULN at screening visit. 5. Availability and willingness of subject to provide written informed consent.

You may not qualify if:

• Use of immunosuppressive therapy requiring use of more than 5mg of prednisone(or equivalent) per day, immunomodulatory therapy (including interferon or thymosin ) or systemic cytotoxic agents within previous 6 months or during the study
• Previous or current lamivudine or adefovir dipivoxil therapy or antiviral therapy with agents demonstrating potential anti-HBV activity
• Clinical signs of decompensated liver disease at screening according to the protocol
• Serum creatinine over 1.5mg per dL
• Alanine aminotransferase (ALT) over 10 times ULN at screening or history of acute exacerbation leading to transient decompensation
• Serum Amylase and/or lipase over 2 times ULN
• Inadequate haematological function
• Anti-HBe or Anti-HBs positive subjects
• Hepatocellular carcinoma as evidenced by the protocol
• Documented evidence of active liver disease
• Any serious or active medical or psychiatric illnesses other than hepatitis B which, in the opinion of the investigator, would interfere with patient treatment, assessment or compliance with the protocol. This would include any uncontrolled clinically significant renal, cardiac, pulmonary, vascular, neurogenic, digestive, metabolic (diabetes, thyroid disorders, adrenal disease), immunodeficiency disorders or cancer.
• Active alcohol or drug abuse or history of alcohol or drug abuse considered by the investigator to be sufficient to hinder compliance with treatment, participation in the study or interpretation of results.
• Planned for liver transplantation or previous liver transplantation
• Receipt of any investigational drug within within 3 months prior to screening.
• Therapy with nephrotoxic drugs or competitors of renal excretion within 2 months prior to study screening or the expectation that patient will receive any of these during the course of the study.

Sponsors & Collaborators

• GlaxoSmithKline: lead

MeSH Terms

Conditions

Hepatitis B, Chronic

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

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 17, 2010
• First Posted: September 20, 2010
• Study Start: December 17, 2004
• Primary Completion: April 28, 2006
• Study Completion: April 28, 2006
• Last Updated: July 2, 2018
• Results First Posted: March 26, 2018

Record last verified: 2017-08