Chronic Hepatitis B, Hepatitis B, Chronic
Conditions
Keywords
Adefovir Dipivoxil(Hepsera), Chronic Hepatitis B (CHB)
Brief summary
This is an open label, single-arm, multi-centre extension study for Korean patients with chronic hepatitis B and compensated liver disease who have completed one-year adefovir dipivoxil treatment in ADF103814. The objective is to assess clinical efficacy and safety of long term (up to 3 years) adefovir dipivoxil 10mg therapy.
Interventions
DRUGadefovir dipivoxil 10mg
Sponsors
GlaxoSmithKline
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Subject has completed ADF103814 and continues with adefovir dipivoxil treatment via prescription without interruption prior enrolment in this extension study. Availability and willingness of subject to provide written informed consent.
Exclusion criteria
Use of immunosuppressive therapy requiring use of more than 5mg of prednisolone(or equivalent) per day, immunomodulatory therapy (including interferon or thymosin) or systemic cytotoxic agents during the study. Previous or current lamivudine or antiviral therapy Clinical signs of decompensated liver disease as indicated by the protocol Inadequate haematological function defined by the protocol - Documented evidence of active liver disease due to other causes Hepatocellular carcinoma as evidenced by the protocol 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 Therapy with nephrotoxic drugs or competitors of renal excretion can be expected during the course of the study. History of hypersensitivity to nucleoside and/or nucleotide analogues. Inability to comply with study requirements as determined by the study investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hepatitis B Virus (HBV) DNA (log10 Copies/mL) Change From Baseline at Week 156 of Adefovir Therapy | Baseline, Week 156 | HBV DNA was tested with Roche Cobas Amplicor HBV monitor test, Lower Limit of Detection 300 copies/mL) after 3 years (156 weeks: Weeks 1-52 in Study ADF103814; Weeks 53-156 in Study 108005) of adefovir therapy). Change from baseline was calculated as the Week 156 value minus the Baseline value. Baseline is defined as the first day of study ADF103814, of which Study 108005 is an extension. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Achieving ALT Normalization at Week 104 & 156 | Week 104, Week 156 | Alanine aminotransferase (ALT) normalization is defined as a value \<= upper limit of normal (ULN) range based on the set of subjects with ALT\>ULN at baseline. The normal range for ALT is 0-40 Units/Liter. |
| Number of Participants Achieving Virological Response at Week 104 & 156 | Week 104, Week 156 | Virological response is defined as HBV DNA level\<300 copies/ml |
| HBV DNA Levels at Each Collection Time Point From Baseline Through Week 156 | Baseline, Weeks 68, 80, 92, 104, 120, 132, 144, 156 | Serum HBV DNA. Baseline is defined as the first day of study ADF103814, of which Study 108005 is an extension. |
| Number of Participants With HBeAg Loss, HBeAg Seroconversion, HBsAg Loss and HBsAg Seroconversion at Week 104 & 156 | Week 104 and 156 | Hepatitis B e antigen (HBeAg) loss, HBeAg seroconversion (defined as HBeAg negative and hepatitis B e antibody \[HBeAb\] positive), hepatitis B surface antigen (HBsAg) loss and HBsAg seroconversion (defined as HBsAg negative and hepatitis B surface antibody \[HBsAb\] positive). HBeAg and HBsAg seroconversion are defined as the loss (becoming negative) of HBeAg and the concurrent appearance of antibodies against HBeAg and the loss of HBsAg and the concurrent appearance of antibodies against HBsAg, respectively. |
| Safety Assessment: Number of Participants With a Serious Adverse Event and an Adverse Event | Treatment Phase (Weeks 53-156) | The number of participants with a serious adverse event and an adverse event is reported. Refer to the adverse event section for details. |
Countries
South Korea
Participant flow
Recruitment details
Study ADF108005 (NCT00403585; 80 subjects enrolled) is an extension of Study ADF103814 (104 subjects enrolled). For several outcome measures, baseline is defined as the first day of Study 103814; thus, baseline data for 104 subjects are provided, even though 80 subjects were enrolled in Study 108005.
Participants by arm
| Arm | Count |
|---|---|
| Adefovir Dipivoxil Adefovir Dipivoxil 10 mg tablets once daily | 104 |
| Total | 104 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Initial Treatment Phase | Lost to Follow-up | 2 |
| Open-Label Phase; Extension Study | HBV DNA Mutation Positive | 4 |
| Open-Label Phase; Extension Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Adefovir Dipivoxil |
|---|---|
| Age Continuous | 35.3 years STANDARD_DEVIATION 10.4 |
| Race/Ethnicity, Customized | 104 Participants |
| Sex: Female, Male Female | 21 Participants |
| Sex: Female, Male Male | 83 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 43 / 80 |
| serious Total, serious adverse events | 2 / 80 |
Outcome results
Primary
Hepatitis B Virus (HBV) DNA (log10 Copies/mL) Change From Baseline at Week 156 of Adefovir Therapy
HBV DNA was tested with Roche Cobas Amplicor HBV monitor test, Lower Limit of Detection 300 copies/mL) after 3 years (156 weeks: Weeks 1-52 in Study ADF103814; Weeks 53-156 in Study 108005) of adefovir therapy). Change from baseline was calculated as the Week 156 value minus the Baseline value. Baseline is defined as the first day of study ADF103814, of which Study 108005 is an extension.
Time frame: Baseline, Week 156
Population: Study ADF103814 Intent-to-Treat (ITT) Population: All subjects regardless of whether or not the subject completed the planned duration of the study will be analyzed with no data exclusion. As baseline is defined as the first day of study ADF103814, all 104 subjects enrolled in this study were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Adefovir Dipivoxil | Hepatitis B Virus (HBV) DNA (log10 Copies/mL) Change From Baseline at Week 156 of Adefovir Therapy | Baseline, n=104 | 7.94 log10 copies/mL | Standard Deviation 1.66 |
| Adefovir Dipivoxil | Hepatitis B Virus (HBV) DNA (log10 Copies/mL) Change From Baseline at Week 156 of Adefovir Therapy | Week 156, n=74 | 3.89 log10 copies/mL | Standard Deviation 1.59 |
| Adefovir Dipivoxil | Hepatitis B Virus (HBV) DNA (log10 Copies/mL) Change From Baseline at Week 156 of Adefovir Therapy | Change from Baseline | -4.16 log10 copies/mL | Standard Deviation 1.79 |
p-value: <0.001Wilcoxon signed rank
Secondary
HBV DNA Levels at Each Collection Time Point From Baseline Through Week 156
Serum HBV DNA. Baseline is defined as the first day of study ADF103814, of which Study 108005 is an extension.
Time frame: Baseline, Weeks 68, 80, 92, 104, 120, 132, 144, 156
Population: Study ADF103814 ITT Population. As baseline is defined as the first day of study ADF103814, all 104 subjects enrolled in this study were analyzed. Some participants were not tested at various weeks.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Adefovir Dipivoxil | HBV DNA Levels at Each Collection Time Point From Baseline Through Week 156 | Baseline, n=104 | 7.94 log 10 copies/mL | Standard Deviation 1.66 |
| Adefovir Dipivoxil | HBV DNA Levels at Each Collection Time Point From Baseline Through Week 156 | Week 68, n=74 | 3.90 log 10 copies/mL | Standard Deviation 1.37 |
| Adefovir Dipivoxil | HBV DNA Levels at Each Collection Time Point From Baseline Through Week 156 | Week 80, n=73 | 3.79 log 10 copies/mL | Standard Deviation 1.36 |
| Adefovir Dipivoxil | HBV DNA Levels at Each Collection Time Point From Baseline Through Week 156 | Week 92, n=77 | 3.99 log 10 copies/mL | Standard Deviation 1.49 |
| Adefovir Dipivoxil | HBV DNA Levels at Each Collection Time Point From Baseline Through Week 156 | Week 104, n=76 | 3.97 log 10 copies/mL | Standard Deviation 1.44 |
| Adefovir Dipivoxil | HBV DNA Levels at Each Collection Time Point From Baseline Through Week 156 | Week 120, n=76 | 3.88 log 10 copies/mL | Standard Deviation 1.44 |
| Adefovir Dipivoxil | HBV DNA Levels at Each Collection Time Point From Baseline Through Week 156 | Week 132, n=78 | 3.93 log 10 copies/mL | Standard Deviation 1.51 |
| Adefovir Dipivoxil | HBV DNA Levels at Each Collection Time Point From Baseline Through Week 156 | Week 144, n=74 | 3.97 log 10 copies/mL | Standard Deviation 1.55 |
| Adefovir Dipivoxil | HBV DNA Levels at Each Collection Time Point From Baseline Through Week 156 | Week 156, n=73 | 3.89 log 10 copies/mL | Standard Deviation 1.59 |
Secondary
Number of Participants Achieving ALT Normalization at Week 104 & 156
Alanine aminotransferase (ALT) normalization is defined as a value \<= upper limit of normal (ULN) range based on the set of subjects with ALT\>ULN at baseline. The normal range for ALT is 0-40 Units/Liter.
Time frame: Week 104, Week 156
Population: ITT Population: some participants were not tested at Weeks 104 or 156.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Adefovir Dipivoxil | Number of Participants Achieving ALT Normalization at Week 104 & 156 | Week 104, n=77 | 63 Participants |
| Adefovir Dipivoxil | Number of Participants Achieving ALT Normalization at Week 104 & 156 | Week 156, n=73 | 65 Participants |
Secondary
Number of Participants Achieving Virological Response at Week 104 & 156
Virological response is defined as HBV DNA level\<300 copies/ml
Time frame: Week 104, Week 156
Population: ITT Population: some participants were not tested at Weeks 104 or 156.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Adefovir Dipivoxil | Number of Participants Achieving Virological Response at Week 104 & 156 | Week 104, n=77 | 20 Participants |
| Adefovir Dipivoxil | Number of Participants Achieving Virological Response at Week 104 & 156 | Week 156, n=73 | 24 Participants |
Secondary
Number of Participants With HBeAg Loss, HBeAg Seroconversion, HBsAg Loss and HBsAg Seroconversion at Week 104 & 156
Hepatitis B e antigen (HBeAg) loss, HBeAg seroconversion (defined as HBeAg negative and hepatitis B e antibody \[HBeAb\] positive), hepatitis B surface antigen (HBsAg) loss and HBsAg seroconversion (defined as HBsAg negative and hepatitis B surface antibody \[HBsAb\] positive). HBeAg and HBsAg seroconversion are defined as the loss (becoming negative) of HBeAg and the concurrent appearance of antibodies against HBeAg and the loss of HBsAg and the concurrent appearance of antibodies against HBsAg, respectively.
Time frame: Week 104 and 156
Population: All participants achieving viological response, defined as an HBV DNA level ≤ 300. Some participants were not tested at various weeks.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Adefovir Dipivoxil | Number of Participants With HBeAg Loss, HBeAg Seroconversion, HBsAg Loss and HBsAg Seroconversion at Week 104 & 156 | Week 104 HBeAg loss, n=77 | 23 Participants |
| Adefovir Dipivoxil | Number of Participants With HBeAg Loss, HBeAg Seroconversion, HBsAg Loss and HBsAg Seroconversion at Week 104 & 156 | Week 104 HBeAg seroconversion, n=77 | 6 Participants |
| Adefovir Dipivoxil | Number of Participants With HBeAg Loss, HBeAg Seroconversion, HBsAg Loss and HBsAg Seroconversion at Week 104 & 156 | Week 104 HBsAg loss, n=77 | 0 Participants |
| Adefovir Dipivoxil | Number of Participants With HBeAg Loss, HBeAg Seroconversion, HBsAg Loss and HBsAg Seroconversion at Week 104 & 156 | Week 104 HBsAg seroconversion, n=77 | 0 Participants |
| Adefovir Dipivoxil | Number of Participants With HBeAg Loss, HBeAg Seroconversion, HBsAg Loss and HBsAg Seroconversion at Week 104 & 156 | Week 156 HBeAg loss, n=73 | 27 Participants |
| Adefovir Dipivoxil | Number of Participants With HBeAg Loss, HBeAg Seroconversion, HBsAg Loss and HBsAg Seroconversion at Week 104 & 156 | Week 156 HBeAg seroconversion, n=73 | 12 Participants |
| Adefovir Dipivoxil | Number of Participants With HBeAg Loss, HBeAg Seroconversion, HBsAg Loss and HBsAg Seroconversion at Week 104 & 156 | Week 156 HBsAg loss, n=73 | 1 Participants |
| Adefovir Dipivoxil | Number of Participants With HBeAg Loss, HBeAg Seroconversion, HBsAg Loss and HBsAg Seroconversion at Week 104 & 156 | Week 156 HBsAg seroconversion, n=73 | 0 Participants |
Secondary
Safety Assessment: Number of Participants With a Serious Adverse Event and an Adverse Event
The number of participants with a serious adverse event and an adverse event is reported. Refer to the adverse event section for details.
Time frame: Treatment Phase (Weeks 53-156)
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Adefovir Dipivoxil | Safety Assessment: Number of Participants With a Serious Adverse Event and an Adverse Event | Serious adverse event | 2 participants |
| Adefovir Dipivoxil | Safety Assessment: Number of Participants With a Serious Adverse Event and an Adverse Event | Adverse event | 43 participants |