Clinical trial NCT01588912: Efficacy of Telbivudine With or Without add-on Tenofovir According to Roadmap Strategy Compare With Entecavir
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Chronic Hepatitis B
Keywords: chronic hepatitis B
HBeAg positive
telbivudine
tenofovir
entecavir
roadmap
Lead sponsor: Pusan National University Yangsan Hospital
Sponsor class: OTHER
First posted: 2012-05-01
Enrollment: 104
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: HBV DNA non-detectability
timeFrame: Week 48
Secondary outcomes:
measure: HBV DNA non-detectability
timeFrame: Week 96
measure: Reduction of HBV DNA from baseline
timeFrame: Week 12, 24, 36, 48, 60, 72, 84 & 96
measure: HBeAg loss or HBeAg seroconversion
timeFrame: Week 48 & 96
measure: HBsAg loss or HBsAg seroconversion
timeFrame: Week 48 & 96
measure: ALT normalization
timeFrame: Week 48 & 96
measure: Accumulate rate of Viral breakthrough
timeFrame: Week 48 & 96
measure: Accumulate rate of Biochemical Breakthrough
timeFrame: Week 48 & 96
measure: Accumulate rate of genotypic mutation in HBV
timeFrame: Week 48 & 96
measure: Change of eGFR from baseline
timeFrame: Week 12, 24, 36, 48, 60, 72, 84 & 96
measure: Accumulate rate of CK abnormal elevation
timeFrame: Week 48 & 96
measure: Accumulate rate of symptom related muscular disease
timeFrame: Week 48 & 96
measure: Accumulate rate of Adverse event or serious adverse event
timeFrame: Week 48 & 96
Other outcomes:
Locations:
city: Busan
country: Korea, Republic of
facility: Byung Chul Yoon
city: Busan
country: Korea, Republic of
facility: Eun Uk Jung
city: Busan
country: Korea, Republic of
facility: Hyun Young Woo
city: Busan
country: Korea, Republic of
facility: Nae-Yun Heo
city: Busan
country: Korea, Republic of
facility: Yang Hyun Baek
city: Changwon
country: Korea, Republic of
facility: Hyun Jin Jo
city: Daegu
country: Korea, Republic of
facility: Byung Seok Kim
city: Daegu
country: Korea, Republic of
facility: Soo Young Park
city: Jinju
country: Korea, Republic of
facility: Hyun Ju Min
city: Yangsan
country: Korea, Republic of
facility: Ki Tae Yoon
Study officials:
affiliation: Pusan National University Yangsan Hospital
name: Ki Tae Yoon, M.D.
role: PRINCIPAL_INVESTIGATOR
References: