Last updated: 11/04/2018 04:32:23
Adefovir Dipivoxil For The Treatment Of Chinese Compensated Chronic Hepatitis B(CHB)Patients
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
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
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Single Group Assignment
Masking:
None (Open Label)
Allocation:
Non-randomized
Primary outcomes:
Number of participants achieving HBV DNA (Hepatitis B Virus Deoxyribonucleic Acid) <1000 copies/milliliter at week 48
Timeframe: Week 48
Secondary outcomes:
Number of HBeAg positive participants achieving histological improvement at week 48
Timeframe: Week 48
Ranked assessment of liver histology in HBeAg positive participants from baseline to week 48
Timeframe: Baseline to Week 48
Change from screening in median serum HBV DNA at Weeks 24 and 48
Timeframe: Weeks 24 and 48
Number of participants achieving ALT (alanine aminotransferase) normalization at week 48
Timeframe: Week 48
Number of HBeAg positive participants achieving HBeAg loss and HBeAg seroconversion at week 48
Timeframe: Week 48
Number of participants with ADV-associated resistance at week 48
Timeframe: Week 48
Interventions:
Drug: adefovir dipivoxil
Enrollment:
1470
Observational study model:
Not applicable
Primary completion date:
2008-04-12
Time perspective:
Not applicable
Clinical publications:
Not applicable
Medical condition
Chronic Hepatitis B
Product
adefovir
Collaborators
Not applicable
Study date(s)
December 2006 to December 2008
Type
Interventional
Phase
4
Participation criteria
Sex
Female & Male
Age
16 - 65 years
Accepts healthy volunteers
No
- 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
- 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.
Inclusion and exclusion criteria
Inclusion criteria:
- 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
- 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
Exclusion criteria:
- 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
- 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 location(s)
Study documents
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Completed
Actual primary completion date
2008-04-12
Actual study completion date
2008-04-12
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
Additional information
Not applicable
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