A Two-year Study of Telbivudine in HBeAg Negative Hepatitis

NCT ID: NCT01521975

Last Updated: 2017-10-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 360 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-01-01
• Study Completion Date: 2014-05-30

Brief Summary

Based on GLOBE study supplying predictability analysis results, ROADMAP strategy provides an individualized telbivudine treatment roadmap strategy designed to achieve optimal viral suppression and low resistance rate in patients with chronic hepatitis B(CHB), which includes adding ADV treatment at different time points according to individual patient response. China CHB Guidelines (China Medical Association 2010) make impress on and confirm LDT ROADMAP strategy particularly, which may be a large potential to expand the naïve patients. We are lack of optimal model in HBeAg(-). In China HBeAg(-) is around 38% of total CHB patients. In GLOBE study, LdT treatment against HBeAg(-) patients with HBV DNA <7log showed a good 2 year efficacy, but we still look forward to more efficient treatment and lower resistance rate. This study complies with the principle of individualized therapy recommended and ethical principles. It is expected that this study design with individualized treatment approach may improve efficacy and lower the resistance rates. In addition, it will provide important information on how to bring greater benefits to patients with CHB.

Detailed Description

This study is an open-label, multicenter, PCR response adaptive clinical study design, with intensification of treatment (addition of adefovir to telbivudine treatment) depending on HBV DNA level at week 24. All patients commence with Telbivudine 600mg daily. At week 24 they will be divided into 2 Groups according to virological response. Patients with PCR detectable HBV DNA will add on ADV(Group I). Patients with PCR undetectable HBV DNA(Group II)will continue telbivudine monotherapy. ADV will not be added on unless viral breakthrough occurs.

Conditions

Hepatitis B, Chronic

Keywords

HBV DNA; LdT; ADV; HBeAg negative hepatitis; CHB

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

HBeAg Negative Hepatitis

HBeAg Negative Hepatitis patients.

Group Type: EXPERIMENTAL

Telbivudine, Adefovir dipivoxil

Intervention Type: DRUG

All patients will take Telbivudine 600 mg PO daily from baseline. Some patients will take Adefovir dipivoxil 10 mg PO daily if they meet the criteria of adding Adefovir dipivoxil.

Interventions

Telbivudine, Adefovir dipivoxil

All patients will take Telbivudine 600 mg PO daily from baseline. Some patients will take Adefovir dipivoxil 10 mg PO daily if they meet the criteria of adding Adefovir dipivoxil.

Intervention Type: DRUG

Other Intervention Names

Sebivo, LDT

Eligibility Criteria

Inclusion Criteria

• Detectable serum HBsAg at the Screening visit and at least 6 months prior
• HBeAg negative at Screening visit
• serum HBV DNA level >2,000 IU/mL at Screening visit
• Elevated serum ALT≥2 ×ULN and <10×ULN at Screening visit (excluding ALT elevations due to non-HBV reasons such as drug, alcohol etc)

Exclusion Criteria

• Patient has a history of clinical signs/symptoms of hepatic decompensation (Child-Pugh Grade B or C) or ascites, esophageal variceal bleeding, hepatic encephalopathy, or spontaneous bacterial peritonitis.
• Patient has a history of hepatocellular carcinoma (HCC) or suspected symptoms of HCC, such as suspicious foci on imaging studies and/or serum alpha-fetoprotein (AFP)>50ng/mL.
• Patient has received treatment of nucleoside or nucleotide drugs whether approved or investigational before.
• Patient has received IFN or other immunomodulatory treatment within 52 weeks before Screening.
• Patient has a medical condition that requires frequent use of systemic acyclovir or famciclovir.
• Patient has a medical condition that requires frequent use of systemic corticosteroids, however topical and inhaled corticosteroids are allowed.
• Patient has used hepatotoxic drugs within one month.
• Patient has overtaken alcohol (>40g/day) or abused illicit drugs in recent one year.
• Use of other investigational drugs at the time of enrollment.
• History of hypersensitivity to any of the study drugs (telbivudine or adefovir).
• Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive urine pregnancy test.
• Patient is co-infected with HCV, HDV or HIV.
• Patient has one or more additional known primary or secondary causes of liver disease, other than hepatitis B (e.g., alcoholism, autoimmune hepatitis).
• History of malignancy of any organ system.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Guangdong Provincial People's Hospital

OTHER

Sponsor Role: collaborator

Guangzhou 8th People's Hospital

OTHER

Sponsor Role: collaborator

Third Affiliated Hospital, Sun Yat-Sen University

OTHER

Sponsor Role: lead

Responsible Party

Chao-Shuang Lin

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Zhi-Liang Gao, Prof

Role: PRINCIPAL_INVESTIGATOR

Third Affiliated Hospital, Sun Yat-Sen University

Locations

The Third Affiliated Hospital of Sun Yat-sen University

Guangzhou, Guangdong, China

Countries

China

References

Gan W, Li J, Zhang C, Chen X, Lin C, Gao Z. Efficacy of 104-week Telbivudine-based optimization strategy in patients with HBeAg-negative chronic hepatitis B virus infections. BMC Infect Dis. 2020 Dec 7;20(1):931. doi: 10.1186/s12879-020-05642-y.

Reference Type: DERIVED

PMID: 33287722 (View on PubMed)

Other Identifiers

HBeAg negative Roadmap

Identifier Type: -

Identifier Source: org_study_id