Chronic Hepatitis BPhase 4NCT00324961
Adefovir Dipivoxil Tablets (10mg) In Chinese Subjects With HBe Antigen Negative Chronic Hepatitis B
A Phase 4 study testing adefovir dipivoxil tablets in people with Chronic Hepatitis B, run by GlaxoSmithKline at 18 sites in China.
Trial summary
This is a phase IV, 2-year, multi-center, single arm and open-label study, evaluating the efficacy and safety with using local manufactured adefovir dipivoxil in Chinese subjects with HBeAg negative chronic hepatitis B Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Chronic Hepatitis B
- What is being tested?
- adefovir dipivoxil tablets
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 533 participants
- Where
- 18 sitesChina
- Study dates
- Jan 2006to Jan 2009
- 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 to 65 years
- All sexes
- No healthy volunteers
- 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 at least 6 months
- Documented HBeAg negative and HBeAb positive at the screening visit and with at least a 6 months history of HBeAg negativity.
- Serum HBV DNA ≥ 104 copies/mL (Roche COBAS AMPLICORTM HBV MONITOR Test, LLOD 300 copies/mL) at study screening (within 4 weeks before baseline)
- ALT value ≥1.3 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 to the study screening.
- Serum alpha fetoprotein (AFP) < 50 ng/mL at the first screening visit. If the AFP level is ≥ 50 ng/mL but declined to < 50 ng/mL between screening and baseline, the patient is eligible.
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- Compensated liver disease with the following laboratory and clinical parameters at study screening:
- Prothrombin time ≤ 2 second above normal range.
- Albumin ≥ 35 g/L.
- Total bilirubin ≤ 2.5 mg/dL (≤ 43 µmol/L) or normal direct bilirubin.
- No history of variceal bleeding.
- No history of encephalopathy.
- No history of ascites
- 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) recommended for the patients who will undergo liver biopsy.
- Hemoglobin ≥ 10 g/dL (≥ 100 g/L) (males) or ≥ 9 g/dL (≥ 9 g/L) (females).
- Willing and able to undergo a minimum of two liver biopsies (prior to dosing, and after 104 weeks of therapy; only apply to subjects who are enrolled to the sites where liver biopsy is required).
- A female is eligible to enter and participate in this study if she is of:
- non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is pre-menarchal or post-menopausal);
- child-bearing potential with a negative serum pregnancy test at screen, and agrees to one of the following: Complete abstinence from intercourse from 2 weeks prior to administration of the study drug, throughout the study, and for a time interval after completion or premature discontinuation from the study to account for elimination of the investigational drug, (a minimum of 5 half-lives or longer if the pharmacodynamic profile of the investigational drug warrants a longer time period); or, Female sterilization; or, Sterilization of male partner; or, Implants of levonorgestrel; or, Injectable progestogen; or, Oral contraceptive (combined or progestogen only); or, Any intrauterine device (IUD) with published data showing that the lowest expected failure rate is less than 1% per year (not all IUDs meet this criterion); or, Any other methods with published data showing that the lowest expected failure rate for that method is less than 1% per year; or, Barrier method only if used in combination with any of the above acceptable methods.
- Agree not to participate in any other investigational trials or to undertake other HBV systemic antiviral regimens during participation in this study
- Able to give written informed consent and comply with the requirements of the study
Who cannot join
- 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 eligible; co-infection with hepatitis delta (HDV); co-infection with HIV; autoimmune hepatitis (antinuclear antibody titre > 1:160)
- Clinical signs of decompensated liver disease at baseline. These may include but are not limited to:
- serum bilirubin > 2.5 mg/dL (≤ 43 µmol/L) - prothrombin time > 2 second prolonged above ULN
- serum albumin < 35g/L
- history of ascites, variceal bleeding, or encephalopathy
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- Alanine aminotransferase (ALT) >10 times ULN at screening or history of acute exacerbation leading to transient decompensation
- 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
- 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, chronic anti-viral agents excluding lamivudine (e.g. ganciclovir, adefovir dipivoxil, entecavir, famciclovir, FTC, DAPD, LFMAU, HBIg), Chinese herbal medicines known to have activity against HBV within the previous 12 months or during the study; use of agents with effect of ALT reduction (e.g. schisandra agents) during the study
- Use of lamivudine within the previous 3 months or during the study
- Planned for liver transplantation or previous liver transplantation
- 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.
- 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.
- Receiving systemic (intravenous or oral) steroids, immuno-suppressant therapies or chemotherapeutic agents within 2 months of study screening or expected to receive these agents during the course of the study.
- History of hypersensitivity to nucleoside and/or nucleotide analogues.
- Inability to comply with study requirements.
- Lactating females or females with a positive serum pregnancy test.
- Organ or bone marrow transplant recipients.
- Previous (or planned) participation in an investigational trial involving administration of investigational compound within 2 months prior to the study screening.
- Can not comply with the requirements of the study
Trial locations and contacts
18 sites in 1 country.
18 sites in 1 country
China18 sites
GSK Investigational Site
Beijing, 100011
GSK Investigational Site
Beijing, 100044
GSK Investigational Site
Beijing, 100050
GSK Investigational Site
Changchun, Jilin, 130021
GSK Investigational Site
Changsha, 410008
GSK Investigational Site
Chongqing, 400038
GSK Investigational Site
Chongquin, 400038
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, 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
Wuhan, Hubei, 430030
About this study
Official title: A 2-year Multi-centre, Open-label, Local Phase IV Study to Demonstrate the Efficacy and Safety of Adefovir Dipivoxil Tablets (10mg) in Chinese Subjects With HBe Antigen Negative Chronic Hepatitis B
This is a phase IV, 2-year, multi-center, single arm and open-label study, evaluating the efficacy and safety with using local manufactured adefovir dipivoxil in Chinese subjects with HBeAg negative chronic hepatitis B
- Conditions
- Chronic Hepatitis B
- Being tested
- adefovir dipivoxil tablets
- Keywords
- adefovir dipivoxil, e Antigen negative, 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 dipivoxil tabletsDrug
adefovir dipivoxil once daily 10 mg orally
| Study group | Role | What they receive |
|---|---|---|
| Single arm open label adefovir dipivoxil | Experimental | adefovir dipivoxil once daily 10 mg orally Receives: Drug: adefovir dipivoxil tablets |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Achieving HBV DNA ≤300 Copies/mL at Week 104
Hepatitis B Virus (HBV) DNA level is tested in blood serum by real-time Polymerase Chain Reaction with the lower limit of detection (LLD) as 300 copies/milliliter in a central laboratory.
Measured: Week 104
Secondary outcomes (9)
Number of Participants Achieving Histological Improvement After the 104-week Treatment
Histological improvement (defined as ≥2 point reduction in the Knodell necroinflammation score without worsening fibrosis) was assessed by 2 independent pathologists in the HBeAg-negative participants who underwent 2 sequential liver biopsies at baseline and week 104/withdrawal. The Knodell/histological activity index (HAI) scoring system represents the sum of scores for periportal, bridging necrosis (0-10: none=0, 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, cirrhosis=4)
Measured: Week 104
Liver Histology Scores in HBeAg Negative Participants With Two Sequential Liver Biopsies During the Period of 104 Weeks
The Knodell/histological activity index (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 independent pathologists in the HBeAg negative participants with 2 sequential liver biopsies during the period of 104 weeks.
Measured: Baseline to Week 104
Change From Baseline in Median Serum HBV DNA Over Time
The HBV DNA level was tested in blood serum by real-time PCR with the LLD as 300 copies/mL at baseline and Weeks 13, 26, 39, 52, 65, 78, 91, and 104 in a central laboratory.
Measured: Baseline and Weeks 13, 26, 39, 52, 65, 78, 91, and 104
Number of Participants Achieving ALT Normalization at Week 104
Serum alanine aminotransferase (ALT) normalization was defined as a serum ALT level at or below the upper limit of the normal (ULN) range after a baseline value above the ULN, as determined using central laboratory ranges.
Measured: Week 104
Number of Participants Achieving HBsAg Loss and HBsAg Seroconversion at Week 104
HBsAg loss and HBsAg seroconversion (HBsAg loss and HBsAb detected) were assessed for all participants who were HBeAg negative at Weeks 0 and 104. Confirmed HBsAg loss was defined as undetectable HBeAg.
Measured: Week 104
Number of Participants With ADV-associated Resistance at Week 104
Week 104 serum samples from participants who reached a HBV DNA breakthrough were assessed for the development of ADV (Adefovir dipivoxil) mutations (N236T and A181V) in the HBV polymerase. HBV DNA breakthrough was defined as an increase in HBV DNA level by 1 log10 copies/mL or more from the treatment nadir during Weeks 0 to 104.
Measured: Week 104
Number of Participants Achieving HBV DNA ≤300 Copies/mL Over Time
Hepatitis B Virus (HBV) DNA level is tested in blood serum by real-time Polymerase Chain Reaction with the lower limit of detection (LLD) as 300 copies/milliliter in a central laboratory.
Measured: Weeks 13, 26, 39, 52, 65, 78, 91, and 104
Number of Participants Achieving Complete Response at Week 104
Complete response was defined as an HBV DNA level ≤ 300 copies/mL by the Roche COBAS AMPLICOR HBV MONITOR Test and ALT normalized for two consecutive visits at least 3 months apart.
Measured: Week 104
Time to Protocol-defined Complete Response Over a 104-week Treatment Period
Time to response was defined as the time to participants achieving protocol-defined complete response at week 104 from baseline. Protocol-defined complete response was an HBV DNA level ≤ 300 copies/mL by Roche COBAS AMPLICOR HBV MONITOR Test and ALT normalized for two consecutive visits at least 3 months apart.
Measured: Baseline to Week 104
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 May 2006 (estimated)
- Study startJan 2006
- Primary completionJan 2009
- Study completionJan 2009
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
- 533 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
- NCT00324961
- Sponsor's protocol ID
- ADF106632
- Status last verified
- Oct 2009
- First submitted
- 9 May 2006
- Last updated
- 28 Oct 2009
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A 2-year Multi-centre, Open-label, Local Phase IV Study to Demonstrate the Efficacy and Safety of Adefovir Dipivoxil Tablets (10mg) in Chinese Subjects With HBe Antigen Negative Chronic Hepatitis B
- ClinicalTrials.gov ID
- NCT00324961
- Acronym / sponsor ID
- ADF106632
- Conditions
- Chronic Hepatitis B
- Keywords
- adefovir dipivoxil, e Antigen negative, chronic hepatitis B, Chinese
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 533 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- Jan 2006
- Primary completion
- Jan 2009 (actual)
- Study completion
- Jan 2009 (actual)
- First posted
- 11 May 2006 (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 is a phase IV, 2-year, multi-center, single arm and open-label study, evaluating the efficacy and safety with using local manufactured adefovir dipivoxil in Chinese subjects with HBeAg negative chronic hepatitis B
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 open label adefovir dipivoxil | Experimental | Drug: adefovir dipivoxil tabletsadefovir dipivoxil once daily 10 mg orally |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- Male or female subjects aged 18-65 years inclusive
- Documented chronic hepatitis B infection determined by the presence of serum HBsAg for at least 6 months
- Documented HBeAg negative and HBeAb positive at the screening visit and with at least a 6 months history of HBeAg negativity.
- Serum HBV DNA ≥ 104 copies/mL (Roche COBAS AMPLICORTM HBV MONITOR Test, LLOD 300 copies/mL) at study screening (within 4 weeks before baseline)
- ALT value ≥1.3 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 to the study screening.
Key exclusion criteria (23 listed)
- 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 eligible; co-infection with hepatitis delta (HDV); co-infection with HIV; autoimmune hepatitis (antinuclear antibody titre > 1:160)
- Clinical signs of decompensated liver disease at baseline. These may include but are not limited to:
- serum bilirubin > 2.5 mg/dL (≤ 43 µmol/L) - prothrombin time > 2 second prolonged above ULN
- serum albumin < 35g/L
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 dipivoxil tabletsadefovir dipivoxil once daily 10 mg orally | Drug | Single arm open label adefovir dipivoxil |
Primary outcome
Number of Participants Achieving HBV DNA ≤300 Copies/mL at Week 104
Time frame: Week 104
Hepatitis B Virus (HBV) DNA level is tested in blood serum by real-time Polymerase Chain Reaction with the lower limit of detection (LLD) as 300 copies/milliliter in a central laboratory.
9 secondary outcomes
Number of Participants Achieving Histological Improvement After the 104-week Treatment
Time frame: Week 104
Liver Histology Scores in HBeAg Negative Participants With Two Sequential Liver Biopsies During the Period of 104 Weeks
Time frame: Baseline to Week 104
Change From Baseline in Median Serum HBV DNA Over Time
Time frame: Baseline and Weeks 13, 26, 39, 52, 65, 78, 91, and 104
Number of Participants Achieving ALT Normalization at Week 104
Time frame: Week 104
Number of Participants Achieving HBsAg Loss and HBsAg Seroconversion at Week 104
Time frame: Week 104
Number of Participants With ADV-associated Resistance at Week 104
Time frame: Week 104
Number of Participants Achieving HBV DNA ≤300 Copies/mL Over Time
Time frame: Weeks 13, 26, 39, 52, 65, 78, 91, and 104
Number of Participants Achieving Complete Response at Week 104
Time frame: Week 104
Time to Protocol-defined Complete Response Over a 104-week Treatment Period
Time frame: Baseline to Week 104
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 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
18 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 tablets in people with Chronic Hepatitis B, run by GlaxoSmithKline at 18 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 24 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 28 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 18 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 ≤300 Copies/mL at Week 104 (time frame: Week 104). 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 28 Oct 2009.