Chronic Hepatitis BPhase 4NCT00441974
Adefovir Dipivoxil For The Treatment Of Chinese Compensated Chronic Hepatitis B(CHB)Patients
A Phase 4 study testing adefovir dipivoxil in people with Chronic Hepatitis B, run by GlaxoSmithKline at 25 sites in China.
Trial summary
This 48-week open-label study of local manufactured adefovir dipivoxil Tablet evaluates the efficacy and safety of adefovir 10mg once daily in Chinese subjects with compensated CHB. Read more about this study
- Who is it for?
- Ages 16 to 65 years
- Conditions the study is for
- Chronic Hepatitis B
- What is being tested?
- adefovir dipivoxil
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,470 participants
- Where
- 25 sitesChina
- Study dates
- Dec 2006to Sep 2008
- 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 16 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Male or female subjects aged 18-65 years inclusive
- Documented chronic hepatitis B infection determined by the presence of serum HBsAg for a least 6 months
- Serum HBV DNA ≥105 copies/ml for HBeAg positive subjects or ≥104 copies/ml for HBeAg negative subjects (Real-time PCR, LLQ=1000cp/ml) at study screening (within 2 weeks before baseline), respectively.
- ALT value ≥2 times the upper limit of normal (ULN) at the time of screening, as determined using laboratory ranges and documented ALT abnormal within 6 month prior the study screening.
- Compensated liver disease with the following laboratory and clinical parameters study screening:
- prothrombin time ≤ 2 seconds above normal direct bilirubin
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- Albumin≥35g/L
- Total bilirubin ≤2.5mg/dL (≤ 43 µmol/L) or normal direct bilirubin
- No history of variceal bleeding
- No history of encephalopathy
- No history of ascites
- Willing and able to undergo two liver biopsies (prior to dosing, and after 48 weeks of therapy; only apply to subjects who are enrolled to the sites where liver biopsy is required).
- Agree not to participate in any other investigational trials or to undertake other HBV systemic antiviral regimens during participation in this study
Who cannot join
- A subject will not be eligible for inclusion in this study if any of the following criteria apply:
- 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, may not limit to, renal, cardiac, pulmonary, vascular, neurogenic, digestive, metabolic (diabetes, thyroid disorders, adrenal disease), immunodeficiency disorders, active infection or cancer.
- Documented evidence of active liver disease due to other causes including
- co-infection hepatitis C (HCV), Subjects who are anti-HCV positive and in whom HCV RNA is undetectable are considered to be HCV seropositive and will not be eligible
- co-infection with hepatitis delta (HDV)
- co-infection with HIV
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- autoimmune hepatitis (antinuclear antibody titre>1:160)
- Alanine aminotransferase(ALT) > 10 times ULN at screening or history of acute exacerbation leading to transient decompensation
- Serum alpha fetoprotein (AFP) >50 ng/mL.
- Hepatocellular carcinoma as evidenced by one of the following:
- suspicious foci on ultrasound or radiological examination
- where no positive ultrasound finding, but serum alpha-fetoprotein > 100ng/ml
- Adequate renal function defined as serum creatinine >1.5 mg/dL (>130 µmol/L)
- Adequate hematological function defined as:
- Absolute neutrophil count <1 x 10³/mm³ (1 x 10^9/L)
- Platelets<80 x 10³/mm³ (80 x 10^9/L); platelets<100 x 10³/mm³ (100 x 10^9/L)
- Hemoglobin<12g/dL (120 g/L)(males) or <10 g/dL (100 g/L) (females)
- 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.
- Use of immunosuppressive therapy, immunomodulatory therapy (including interferon or thymosin), systemic cytotoxic agents within the previous 6 months or during the study.
- Use of chronic anti-viral agents(e.g. lamivudine, adefovir dipivoxil, entecavir, famciclovir, tenofovir, FTC, ganciclovir, DAPD, LfMA, HBIg, etc.), Chinese herbal medicines known to have activity against HBV within the previous 3 months or during the study; use of agents with effect of ALT reduction (e.g. schisandra agents) during the study.
- Received nephrotoxic drugs (e.g., aminoglycosides, amphotericin B, vancomycin, cidofovir, foscarnet, cis-platinum, pentamidine etc.) or competitors of renal excretion (e.g., probenecid within 2 months prior to study screening or the expectation that patient will receive any of these during the course of the study.
- Received hepatotoxic drugs (e.g., anabolic steroids, ketaconazole, itraconazole, isoniazid, rifampin, rifabutin) within 2 months prior to study screening or expected to receive these during the course of the study.
- Previous (or planned) participation in an investigational trial involving administration of investigational compound within 2 months prior to the study screening.
Trial locations and contacts
25 sites in 1 country.
25 sites in 1 country
China25 sites
GSK Investigational Site
Beijing, 100011
GSK Investigational Site
Beijing, 100044
GSK Investigational Site
Beijing, 100050
GSK Investigational Site
Beijing, 100069
GSK Investigational Site
Changchun, Jilin, 130021
GSK Investigational Site
Changsha, 410008
GSK Investigational Site
Changsha, 410011
GSK Investigational Site
Chengdu, Sichuan, 610041
GSK Investigational Site
Chongqing, 400038
GSK Investigational Site
Chongquin, 400038
GSK Investigational Site
Fuzhou, 350025
GSK Investigational Site
Guangzhou, Guangdong, 510515
GSK Investigational Site
Guangzhou, Guangdong, 510630
GSK Investigational Site
Hangzhou, Zhejiang, 310003
GSK Investigational Site
Jinan, 250021
GSK Investigational Site
Nanjing, Jiangsu, 210002
GSK Investigational Site
Nanjing, Jiangsu, 210003
GSK Investigational Site
Nanjing, Jiangsu, 210029
GSK Investigational Site
Shanghai, 200001
GSK Investigational Site
Shanghai, 200003
GSK Investigational Site
Shanghai, 200025
GSK Investigational Site
Shanghai, 200040
GSK Investigational Site
Shanghai, 200433
GSK Investigational Site
Tianjin, 300192
GSK Investigational Site
Wuhan, Hubei, 430030
About this study
Official title: A 48-week Multi-centre, Open-label, Local Phase IV Study to Demonstrate the Efficacy and Safety of Adefovir Dipivoxil Tablets (10mg) in Chinese Subjects With Compensated Chronic Hepatitis B
This 48-week open-label study of local manufactured adefovir dipivoxil Tablet evaluates the efficacy and safety of adefovir 10mg once daily in Chinese subjects with compensated CHB. Primary endpoint is proportion of subjects achieving HBV DNA undetectable (<=1000 copies/mL by by Roche COBAS AMPLICOR HBV MONITOR Test) at week 48. Approximately 1250 patients will be recruited in 30 study centers in China. The subjects are offered 48 weeks of open label adefovir dipivoxil treatment, with assessments every three months, after with is a 12-week post study treatment follow-up prior to study completion.
- Conditions
- Chronic Hepatitis B
- Being tested
- adefovir dipivoxil
- Keywords
- adefovir dipivoxil, compensated, chronic hepatitis B, Chinese
- 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.
adefovir dipivoxilDrug
adefovir dipivoxil once daily one tablet 10mg orally
| Study group | Role | What they receive |
|---|---|---|
| Single arm adefovir dipivoxil | Experimental | adefovir dipivoxil once daily orally 10 mg Receives: Drug: adefovir dipivoxil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Achieving HBV DNA (Hepatitis B Virus Deoxyribonucleic Acid) <1000 Copies/Milliliter at Week 48
HBV (Hepatitis B Virus) DNA level was tested by real-time Polymerase Chain Reaction at Week 48.
Measured: Week 48
Secondary outcomes (6)
Number of HBeAg Positive Participants Achieving Histological Improvement at Week 48
Histological improvement (defined as a ≥2 point reduction in the Knodell necroinflammation score without worsening fibrosis) was accessed by two pathologists in HBeAg-positive participants undergoing liver biopsy at baseline and week 48/withdrawal. Knodell/Histological Activity Index (HAI) score = combined scores for necrosis, inflammation, and fibrosis and is the sum of scores for periportal bridging necrosis (0-10: none=0, multilobular necrosis=10), intralobular degeneration and focal necrosis and portal inflammation (0-4: none=0, marked=4), and fibrosis (0-4: none=0, cirrhosis=4).
Measured: Week 48
Ranked Assessment of Liver Histology in HBeAg Positive Participants From Baseline to Week 48
A ranked assessment with the Knodell/HAI scoring system that represents the sum of scores for periportal bridging necrosis (0-10: none=0, moderate piecemeal necrosis plus bridging necrosis=5, multilobular necrosis=10); interlobular degeneration and focal necrosis (0-4: none=0, marked=4); portal inflammation (0-4: none=0, marked=4) and fibrosis (0-4: none=0, fibrous portal expansion=1, bridging fibrosis=3, cirrhosis=4) was carried out by two pathologists in the HBeAg positive participants who underwent liver biopsy at baseline and Week 48/withdrawal.
Measured: Baseline to Week 48
Change From Screening in Median Serum HBV DNA at Weeks 24 and 48
The HBV DNA level was tested in blood serum by real-time Polymerase Chain Reaction with the LLD (lower limit of detection) as 300 copies/milliliter (cp/mL) at screening, week 24, and week 48 in a central laboratory. The change in HBV DNA from screening to week 24 and week 48 was conducted.
Measured: Weeks 24 and 48
Number of Participants Achieving ALT (Alanine Aminotransferase) Normalization at Week 48
Elevated serum ALT levels are defined as serum ALT levels greater than the upper limit of the normal range (ULN), as determined using local laboratory ranges. ALT normalization was defined as ALT measurements at or below the ULN after a baseline value above the ULN.
Measured: Week 48
Number of HBeAg Positive Participants Achieving HBeAg Loss and HBeAg Seroconversion at Week 48
HBeAg loss and HBeAg seroconversion (HBeAg loss and HBeAb detected) were assessed in participants who were HBeAg positive at Weeks 0 and 48. Confirmed HBeAg loss was defined as undetectable HBeAg.
Measured: Week 48
Number of Participants With ADV-associated Resistance at Week 48
Week 48 serum samples from participants, who reached a HBV DNA breakthrough or have HBV DNA≥5 log copies/mL at Weeks 24 and 48 were assessed for the development of ADV (Adefovir dipivoxil) mutation (N236T and A181V) in the HBV polymerase. Virologic breakthrough was defined as an increase in the level of HBV DNA 1 log10 copy/mL from Week 24 to Week 48. ADV-associated resistance was defined as participants with both virologic breakthrough and ADV mutation.
Measured: Week 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Mar 2007 (estimated)
- Study startDec 2006
- Primary completionSep 2008
- Study completionSep 2008
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 Chronic Hepatitis BStudies 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1,470 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00441974
- Sponsor's protocol ID
- ADF108356
- Status last verified
- Oct 2009
- First submitted
- 28 Feb 2007
- Last updated
- 20 Oct 2009
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 20 Oct 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A 48-week Multi-centre, Open-label, Local Phase IV Study to Demonstrate the Efficacy and Safety of Adefovir Dipivoxil Tablets (10mg) in Chinese Subjects With Compensated Chronic Hepatitis B
- ClinicalTrials.gov ID
- NCT00441974
- Acronym / sponsor ID
- ADF108356
- Conditions
- Chronic Hepatitis B
- Keywords
- adefovir dipivoxil, compensated, chronic hepatitis B, Chinese
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,470 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- Dec 2006
- Primary completion
- Sep 2008 (actual)
- Study completion
- Sep 2008 (actual)
- First posted
- 1 Mar 2007 (estimated)
- Results
- Posted 2 Oct 2009
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This 48-week open-label study of local manufactured adefovir dipivoxil Tablet evaluates the efficacy and safety of adefovir 10mg once daily in Chinese subjects with compensated CHB. Primary endpoint is proportion of subjects achieving HBV DNA undetectable (<=1000 copies/mL by by Roche COBAS AMPLICOR HBV MONITOR Test) at week 48. Approximately 1250 patients will be recruited in 30 study centers in China. The subjects are offered 48 weeks of open label adefovir dipivoxil treatment, with assessments every three months, after with is a 12-week post study treatment follow-up prior to study completion.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single arm adefovir dipivoxil | Experimental | Drug: adefovir dipivoxiladefovir dipivoxil once daily orally 10 mg |
Who may qualify
- Ages
- 16 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (13 listed)
- Male or female subjects aged 18-65 years inclusive
- Documented chronic hepatitis B infection determined by the presence of serum HBsAg for a least 6 months
- Serum HBV DNA ≥105 copies/ml for HBeAg positive subjects or ≥104 copies/ml for HBeAg negative subjects (Real-time PCR, LLQ=1000cp/ml) at study screening (within 2 weeks before baseline), respectively.
- ALT value ≥2 times the upper limit of normal (ULN) at the time of screening, as determined using laboratory ranges and documented ALT abnormal within 6 month prior the study screening.
- Compensated liver disease with the following laboratory and clinical parameters study screening:
Key exclusion criteria (23 listed)
- A subject will not be eligible for inclusion in this study if any of the following criteria apply:
- 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, may not limit to, renal, cardiac, pulmonary, vascular, neurogenic, digestive, metabolic (diabetes, thyroid disorders, adrenal disease), immunodeficiency disorders, active infection or cancer.
- Documented evidence of active liver disease due to other causes including
- co-infection hepatitis C (HCV), Subjects who are anti-HCV positive and in whom HCV RNA is undetectable are considered to be HCV seropositive and will not be eligible
- co-infection with hepatitis delta (HDV)
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 |
|---|---|---|
| adefovir dipivoxiladefovir dipivoxil once daily one tablet 10mg orally | Drug | Single arm adefovir dipivoxil |
Primary outcome
Number of Participants Achieving HBV DNA (Hepatitis B Virus Deoxyribonucleic Acid) <1000 Copies/Milliliter at Week 48
Time frame: Week 48
HBV (Hepatitis B Virus) DNA level was tested by real-time Polymerase Chain Reaction at Week 48.
6 secondary outcomes
Number of HBeAg Positive Participants Achieving Histological Improvement at Week 48
Time frame: Week 48
Ranked Assessment of Liver Histology in HBeAg Positive Participants From Baseline to Week 48
Time frame: Baseline to Week 48
Change From Screening in Median Serum HBV DNA at Weeks 24 and 48
Time frame: Weeks 24 and 48
Number of Participants Achieving ALT (Alanine Aminotransferase) Normalization at Week 48
Time frame: Week 48
Number of HBeAg Positive Participants Achieving HBeAg Loss and HBeAg Seroconversion at Week 48
Time frame: Week 48
Number of Participants With ADV-associated Resistance at Week 48
Time frame: Week 48
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Oct 2009.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Chronic Hepatitis B
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
25 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing adefovir dipivoxil in people with Chronic Hepatitis B, run by GlaxoSmithKline at 25 sites in China.
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 13 inclusion and 23 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 20 Oct 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 25 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
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 2 Oct 2009). 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?
Number of Participants Achieving HBV DNA (Hepatitis B Virus Deoxyribonucleic Acid) <1000 Copies/Milliliter at Week 48 (time frame: Week 48). 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 20 Oct 2009.