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

Chronic Hepatitis B Clinical Trial

— TETRA  

Official title:

A Randomized, Prospective, Multicenter, Open-label Study to Evaluate the Efficacy of Telbivudine With or Without add-on Tenofovir According to Roadmap Strategy Compare With Entecavir in HBeAg-positive Chronic Hepatitis B Patients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01588912
• Other study ID #: CLDT600AKR07T
• Status: Recruiting
• Phase: Phase 4
• First received: April 27, 2012
• Last updated: April 30, 2012
• Start date: April 2012
• Est. completion date: December 2014

Study information

• Verified date: April 2012
• Source: Pusan National University Yangsan Hospital
• Contact: Ki Tae Yoon, M.D.
• Phone: 82-55-360-2362
• Email: ktyoon[@]pusan.ac.kr
• Is FDA regulated: No
• Health authority: Korea: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Description:

104 treatment-naïve patients with HBeAg-positive chronic hepatitis B who fulfill the inclusion criteria will be randomized in a 1:1 ratio to receive either Telbivudine 600mg monotherapy or Entecavir monotherapy with stratification before randomization according to presence of cirrhosis. For Telbivudine group, Telbivudine monotherapy or Tenofovir combined therapy will be done according to virologic response at 24 weeks and the primary study will be completed at Week 48 and treatment response will be analyzed. The treatment will be extended to Week 96 and the secondary analysis will be performed then.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 104
• Est. completion date: December 2014
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

• History of any other acute or chronic medical condition that in the opinion of the investigator would make the patient unsuitable for inclusion into the study

• 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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Hepatitis B
• Hepatitis
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• Telbivudine
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
• Tenofovir
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
• Entecavir
Maintain the entecavir through the study period

Locations

Country	Name	City	State
Korea, Republic of	Byung Chul Yoon	Busan
Korea, Republic of	Eun Uk Jung	Busan
Korea, Republic of	Hyun Young Woo	Busan
Korea, Republic of	Nae-Yun Heo	Busan
Korea, Republic of	Yang Hyun Baek	Busan
Korea, Republic of	Hyun Jin Jo	Changwon
Korea, Republic of	Byung Seok Kim	Daegu
Korea, Republic of	Soo Young Park	Daegu
Korea, Republic of	Hyun Ju Min	Jinju
Korea, Republic of	Ki Tae Yoon	Yangsan

Sponsors (1)

Lead Sponsor	Collaborator
Pusan National University Yangsan Hospital

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	HBV DNA non-detectability	Low detection limit of HBV DNA is 50 IU/mL	Week 48	No
Secondary	HBV DNA non-detectability	Low detection limit of HBV DNA is 50 IU/mL	Week 96	No
Secondary	Reduction of HBV DNA from baseline		Week 12, 24, 36, 48, 60, 72, 84 & 96	No
Secondary	HBeAg loss or HBeAg seroconversion		Week 48 & 96	No
Secondary	HBsAg loss or HBsAg seroconversion		Week 48 & 96	No
Secondary	ALT normalization		Week 48 & 96	No
Secondary	Accumulate rate of Viral breakthrough		Week 48 & 96	No
Secondary	Accumulate rate of Biochemical Breakthrough		Week 48 & 96	No
Secondary	Accumulate rate of genotypic mutation in HBV		Week 48 & 96	No
Secondary	Change of eGFR from baseline		Week 12, 24, 36, 48, 60, 72, 84 & 96	No
Secondary	Accumulate rate of CK abnormal elevation		Week 48 & 96	Yes
Secondary	Accumulate rate of symptom related muscular disease		Week 48 & 96	Yes
Secondary	Accumulate rate of Adverse event or serious adverse event		Week 48 & 96	Yes