Efficacy of Telbivudine With or Without add-on Tenofovir According to Roadmap Strategy Compare With Entecavir

NCT01588912 | Unknown Phase 4

• 1 other identifier: CLDT600AKR07T
• Study Type: interventional
• Target: 104
• Locations: 1 country
• Sites: 10

Brief Summary

Oral antiviral drugs which can be given to patients with HBeAg-positive chronic hepatitis B include Lamivudine, Clevudine, Adefovir, Telbivudine, Entecavir and Tenofovir. 2009 American Association for the Study of Liver Disease (AASLD) Treatment Guidelines and 2009 European association for the Study of the Liver (EASL) Treatment Guidelines recommend the administration of Entecavir or Tenofovir with high potency and low resistance. Lamivudine has low antiviral potency and high incidence of mutation in long-term administration compared to Entecavir or Tenofovir. Clevudine causes the elevated creatinine kinase (CK), side effects including myositis/myopathy and much mutation in the long-term administration. Globe study demonstrated Telbivudine had more excellent antiviral potency than Lamivudine, which was also comparable to or higher than Entecavir or Tenofovir. Nevertheless, the choice of treatment drugs can be limited due to the mutation rate of 25% for 2 years. However, the analysis of Globe study results showed that 2-year treatment progress was very good in patient who showed virologic response at 24 weeks after the initiation of treatment and that high antiviral potency and low mutation rate were observed when the Telbivudine roadmap strategy (in the event that virologic response is shown at 24 weeks, telbivudine monotherapy is maintained and in the event that virologic response is not shown, tenofovir add-on therapy is done) recently implemented and announced in 2011 Asian Pacific Association for the Study of the Liver (APASL) was applied. However, the study was single arm study, which restricted the comparison between Entecavir and Tenofovir monotherapy groups. Therefore, this study intends to compare the anti-viral effect and mutation rate between Entecavir 0.5mg monotherapy group and Telbivudine roadmap strategy group in patients with HBeAg-positive chronic hepatitis B through a randomized study.

Conditions

Chronic Hepatitis B

Keywords

chronic hepatitis B; HBeAg positive; telbivudine; tenofovir; entecavir; roadmap

Outcome Measures

Primary Outcomes (1)

• HBV DNA non-detectability

  Low detection limit of HBV DNA is 50 IU/mL

  Week 48

Secondary Outcomes (12)

• HBV DNA non-detectability

  Week 96

• Reduction of HBV DNA from baseline

  Week 12, 24, 36, 48, 60, 72, 84 & 96

• HBeAg loss or HBeAg seroconversion

  Week 48 & 96

• HBsAg loss or HBsAg seroconversion

  Week 48 & 96

• ALT normalization

  Week 48 & 96

Study Arms (2)

Telbivudine-Tenofovir roadmap

EXPERIMENTAL

Drug: Telbivudine; Drug: Tenofovir

Entecavir

ACTIVE COMPARATOR

Drug: Entecavir

Interventions

Telbivudine DRUG

If virologic response, which means HBV DNA \< 50 IU/mL, is shown at 24 weeks, telbivudine monotherapy is maintained and in the event that virologic response is not shown, tenofovir add-on therapy is done

Also known as: Sebivo

Telbivudine-Tenofovir roadmap

Tenofovir DRUG

If virologic response, which means HBV DNA \< 50 IU/mL, is shown at 24 weeks, telbivudine monotherapy is maintained and in the event that virologic response is not shown, tenofovir add-on therapy is done

Also known as: Viread

Telbivudine-Tenofovir roadmap

Entecavir DRUG

Maintain the entecavir through the study period

Also known as: Baraclude

Entecavir

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, at least 18 years of age
• Documented CHB defined by HBsAg or HBeAg positive at least 6 month prior
• HBsAg positive at screening visit
• HBeAg positive and Anti-HBe negative at screening visit
• Serum HBV DNA 20,000\~200,000,000 IU/mL as determined by Realtime PCR at screening visit
• Serum ALT 80\~400 IU/mL at screening visit
• Patient is willing and able to comply with the study drug regimen and all other study requirements
• Patient is willing and able to provide written informed consent to participate in the study

You may not qualify if:

• Patient has received interferon, pegylated interferon, nucleoside or nucleotide drugs at any time
• Patient is co-infected with HCV, HDV, or HIV
• Patient with Child Pugh B or C (Child Pugh score ≥ 7)
• Patient has a history of or clinical signs/symptoms of hepatic decompensation such as ascites, esophageal variceal bleeding, hepatic encephalopathy
• Patient has any of the following laboratory values at screening visit:
• Hemoglobin \<10 g/dL
• Absolute neutrophil count (ANC) \<1,500/mm3
• Platelet count \<70,000/mm3
• Patient has a history of clinical and laboratory evidence of chronic renal insufficiency defined as an estimated serum creatinine clearance \< 50 mL/min using the MDRD formula at screening visit
• Patient is pregnant or breastfeeding
• Patient with currently abusing illegal drugs or alcohol sufficient
• Patient has organ transplantation
• Patient has one or more additional known primary or secondary causes of liver disease, other than CHB, including steatohepatitis and autoimmune hepatitis
• Patient, if AFP is \>50ng/mL at screening visit, has image findings suggestive of HCC at Liver CT or Liver MRI
• Patient with hypersensitivity for study drug

Sponsors & Collaborators

• Pusan National University Yangsan Hospital: lead

Study Sites (10)

Byung Chul Yoon

Busan, South Korea

NOT YET RECRUITING

Eun Uk Jung

Busan, South Korea

NOT YET RECRUITING

Hyun Young Woo

Busan, South Korea

NOT YET RECRUITING

Nae-Yun Heo

Busan, South Korea

NOT YET RECRUITING

Yang Hyun Baek

Busan, South Korea

NOT YET RECRUITING

Hyun Jin Jo

Changwon, South Korea

NOT YET RECRUITING

Byung Seok Kim

Daegu, South Korea

NOT YET RECRUITING

Soo Young Park

Daegu, South Korea

NOT YET RECRUITING

Hyun Ju Min

Jinju, South Korea

NOT YET RECRUITING

Ki Tae Yoon

Yangsan, South Korea

RECRUITING

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

Telbivudine; Tenofovir; entecavir

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thymidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Ki Tae Yoon, M.D.

  Pusan National University Yangsan Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ki Tae Yoon, M.D.

CONTACT

82-55-360-2362; ktyoon@pusan.ac.kr

Surin Tak

CONTACT

82-55-360-1738; surintak@hanmail.net

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: April 27, 2012
• First Posted: May 1, 2012
• Study Start: April 1, 2012
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2014
• Last Updated: May 2, 2012

Record last verified: 2012-04

Locations

KR (10)