Hepatitis B, ChronicPhase 4NCT01205165
An Open Label, Multi Centre Phase IV Study of Adefovir Dipivoxil in Korean Patients With Chronic Hepatitis B (CHB)
A Phase 4 study testing Adefor dipivoxil in people with Hepatitis B, Chronic, run by GlaxoSmithKline.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatitis B, Chronic
- What is being tested?
- Adefor dipivoxil
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 104 participants
- Where
- No sites listed yet
- Study dates
- 17 Dec 2004to 28 Apr 2006
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- A subject will be eligible for inclusion in this study only if all of the following criteria apply:
- 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
- 4. 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.
Who cannot join
- A subject will not be eligible for inclusion in this study if any of the following criteria apply:
- 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
Show all 18Show fewer
- 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.
- History of hypersensitivity to nucleoside and/or nucleotide analogues.
- Inability to comply with study requirements as determined by the study investigator.
About this study
Official title: An Open Label, Multicenter Phase IV Study of Adefovir Dipivoxil in Korean Patients With Chronic Hepatitis B (CHB)
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".
Read more
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
- Being tested
- Adefor dipivoxil
- Medical subject headings
- Hepatitis B, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Adefor dipivoxilDrug
All enrolled subjects were enrolled to adefovir dipivoxil arm.
| Study group | Role | What they receive |
|---|---|---|
| Adefovir Dipivoxil 10mg | Experimental | All enrolled subject were enrolled to adefovir dipivoxil 10mg arm. Receives: Drug: Adefor dipivoxil |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline (Day 1) and Week 12
Secondary outcomes (9)
Number of Participants Achieving Alanine Aminotransferase (ALT) Normalization at Week 52
ALT normalization was defined as measurement less than or equal to the upper limit of the normal range. Only those set of participants with a baseline ALT value above the upper limit of the normal range was included in this analysis. The normal range for ALT is 7 to 43 Units/Liter.
Measured: At week 52
Number of Participants Achieving Virological Response at Week 52
Virological response was defined as HBV DNA level < 300 copies/ml in serum. The number of participants achieving these DNA levels were reported.
Measured: At Week 52
HBV DNA Levels at Each Collection Timepoint Through Week 52
Serum HBV DNA at different timepoints namely Baseline, Week 4, week 8, week 12, week 20, week 28, week 36, week 44 and week 52 were reported. The HBV DNA copies in the serum were reported in multiples of log 10 copies per mL, detected using Roche COBAS AMPLICOR HBV monitor.
Measured: 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
The HBeAg loss, defined as the number of participants with an undetectable level of serum HBeAg. The percentage of participants with a HBeAg seroconversion, defined as an undetectable level of serum HBeAg and a detectable level of serum hepatitis B e antibody (HBeAb) at Week 52. The number of participants with HBsAg loss was defined as an undetectable level of serum HBsAg; and those participants with HBsAg seroconversion were defined as an undetectable level of serum HBsAg and a detectable level of serum HBsAb. All these participant were reported at week 52. Only the subset of participants, with above parameters detectable at baseline were included and for participants with post-baseline values missing were considered as non-responders.
Measured: Week 52
Number of Participants Achieving ALT Normalization at Week 12
ALT normalization was defined as measurement less than or equal to the upper limit of the normal range. The normal range for ALT is 7-43 Units/Liter. Only those set of participants with a baseline ALT value above the upper limit of the normal range were included in this analysis, done at week 12.
Measured: at Week 12
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAEs)
AE is defined as, any untoward medical occurrence in a participant or clinical investigation, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that at any dose, results in death; is life threatening; requires hospitalization or prolongation of hospitalization; results in disability or incapacity, is a congenital anomaly/birth defect or requires medical intervention.
Measured: From treatment initiation (Week 0) to follow-up (up to 52 weeks)
Number of Participants With Shift From Baseline Hematology Parameters at Week 12 and Week 52
The data for hematology parameters was summarized for Hemoglobin, Red blood cells (RBC), Platelets, Neutrophils, Lymphocytes, Monocytes, and Eosinophil as per the scheduled assessments and also according to maximum grade common terminology criteria (CTC) toxicity grade. The data for number of participants with shift in grade for hematology parameters at Week 12 and Week 52 were reported.
Measured: Baseline (Day 1), Week 12 and Week 52
Number of Participants With Shift From Baseline Clinical Chemistry Parameters at Week 12 and Week 52
The data for clinical chemical parameters namely sodium, potassium, calcium, phosphorus, total protein, albumin, amylase, creatinine phospho kinase, creatinine, blood urea nitrogen, total bilirubin, alkaline phosphatase, aspartate transaminase, alanine transaminase, and prothrombin time as per the scheduled assessments and also according to maximum CTC toxicity grade was reported. The data for number of participants with shift in grade for clinical chemistry parameters at Week 12 and Week 52 were reported.
Measured: Baseline (Day 1), Week 12 and Week 52
Mean Log 10 Reduction in Serum HBV DNA Level From Baseline to Week 52
HBV DNA was tested with Roche Cobas Amplicor HBV monitor test, HBV DNA was tested with Roche Cobas Amplicor HBV monitor test, Lower Limit of Detection 300 copies/mL), at baseline and other study visits. The mean log 10 reduction in serum HBV DNA level from baseline to Week 52 was calculated as the Week 52 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
Measured: Baseline (Day 1) and Week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Sep 2010 (estimated)
- Study start17 Dec 2004
- Primary completion28 Apr 2006
- Study completion28 Apr 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hepatitis B, ChronicStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 104 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01205165
- Sponsor's protocol ID
- 103814
- Status last verified
- Aug 2017
- First submitted
- 17 Sep 2010
- Last updated
- 2 Jul 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label, Multicenter Phase IV Study of Adefovir Dipivoxil in Korean Patients With Chronic Hepatitis B (CHB)
- ClinicalTrials.gov ID
- NCT01205165
- Acronym / sponsor ID
- 103814
- Conditions
- Hepatitis B, Chronic
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 104 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 17 Dec 2004 (actual)
- Primary completion
- 28 Apr 2006 (actual)
- Study completion
- 28 Apr 2006 (actual)
- First posted
- 20 Sep 2010 (estimated)
- Results
- Posted 26 Mar 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Adefovir Dipivoxil 10mg | Experimental | Drug: Adefor dipivoxilAll enrolled subject were enrolled to adefovir dipivoxil 10mg arm. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- A subject will be eligible for inclusion in this study only if all of the following criteria apply:
- 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
- 4. 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.
Key exclusion criteria (18 listed)
- A subject will not be eligible for inclusion in this study if any of the following criteria apply:
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Adefor dipivoxilAll enrolled subjects were enrolled to adefovir dipivoxil arm. | Drug | Adefovir Dipivoxil 10mg |
Primary outcome
Mean Log 10 Reduction in Serum Hepatitis B Virus (HBV), Deoxyribonucleic Acid (DNA) Level From Baseline to Week 12
Time frame: Baseline (Day 1) and 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.
9 secondary outcomes
Number of Participants Achieving Alanine Aminotransferase (ALT) Normalization at Week 52
Time frame: At week 52
Number of Participants Achieving Virological Response at Week 52
Time frame: At Week 52
HBV DNA Levels at Each Collection Timepoint Through Week 52
Time frame: 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
Time frame: Week 52
Number of Participants Achieving ALT Normalization at Week 12
Time frame: at Week 12
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAEs)
Time frame: From treatment initiation (Week 0) to follow-up (up to 52 weeks)
Number of Participants With Shift From Baseline Hematology Parameters at Week 12 and Week 52
Time frame: Baseline (Day 1), Week 12 and Week 52
Number of Participants With Shift From Baseline Clinical Chemistry Parameters at Week 12 and Week 52
Time frame: Baseline (Day 1), Week 12 and Week 52
Mean Log 10 Reduction in Serum HBV DNA Level From Baseline to Week 52
Time frame: Baseline (Day 1) and Week 52
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Adefor dipivoxil in people with Hepatitis B, Chronic, run by GlaxoSmithKline.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Mar 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean Log 10 Reduction in Serum Hepatitis B Virus (HBV), Deoxyribonucleic Acid (DNA) Level From Baseline to Week 12 (time frame: Baseline (Day 1) and Week 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2018.