Overview

This trial is active, not recruiting.

Condition chronic hepatitis b
Treatments group a (zeffix, sebivo, hepsera), group b (baraclude, viread)
Phase phase 4
Sponsor Yonsei University
Collaborator Bristol-Myers Squibb
Start date August 2012
End date May 2014
Trial size 104 participants
Trial identifier NCT01597934, AI463-274

Summary

Switching to Entecavir(ETV) plus Tenofovir Disoproxil Fumarate(TDF) combination will result in faster and greater antiviral activity and lower rates of resistance emergence over maintaining Lamivudine(LAM)/Telbivudine(LdT)+Adefovir(ADV) combination in partial responders to LAM/LdT+ADV rescue therapy.

Earlier switching to combination with the most potent regimen will be more effective to achieve virologic response(VR) and prevent further resistance emergence.

All subjects will orally take assigned drugs once daily for 48 weeks. All subjects will be assessed at baseline and every three months thereafter. Evaluations at each visit will include vital signs, physical examinations, laboratory tests, HBV DNA levels and adverse events. At baseline and every six months thereafter, serum will be assayed for HBV serology. Genotypic analysis will be performed at baseline and 48 weeks.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Active Comparator)
Maintaining LAM/LdT+ADV combination Lamivudine 100mg / Telbivudine 600mg +Adefovir 10mg
group a (zeffix, sebivo, hepsera) Zeffix
Maintaining LAM/LdT+ADV combination Lamivudine 100mg / Telbivudine 600mg +Adefovir 10mg
(Experimental)
Switching to ETV plus TDF combination Entecavir 1.0mg + Tenofovir 300mg
group b (baraclude, viread) Baraclude
Switching to ETV plus TDF combination Entecavir 1.0mg + Tenofovir 300mg

Primary Outcomes

Measure
The proportion of subjects who achieve virologic response(HBV DNA < 60 IU/mL, approximately 300 copies/mL) by real-time PCR at Week 48
time frame: at Week 48

Secondary Outcomes

Measure
Virologic efficacy
time frame: Week 12, 24, 36, and 48
serologic efficacy
time frame: Week 12, 24, 36, and 48
biochemical efficacy
time frame: Week 12, 24, 36, and 48
Safety issue
time frame: Week 12, 24, 36, and 48

Eligibility Criteria

Male or female participants at least 20 years old.

Inclusion Criteria: 1. ≥ 20 years of age 2. History of HBsAg positive for more than 6 months 3. History of genotypic resistance to LAM or LdT (YMDDm) 4. Partial responder (HBV DNA ≥ 60 IU/mL) currently receiving antiviral combination rescue therapy for at least 24 weeks of treatment with LAM+ADV or LdT+ADV 5. Hepatitis B e Antigen(HBeAg)-positive and -negative 6. Compensated liver disease (Child-Pugh A) 7. Signed written informed consent after being instructed about the objective and procedure of the clinical study Exclusion Criteria: 1. History of genotypic resistance to ADV 2. Most previous treatment of other than LAM+ADV and LdT+ADV 3. Subjects with Alanine Aminotransferase(ALT) > 10xUpper Limit of normal(ULN) 4. Co-infected with hepatitis C virus(HCV) or HIV 5. Pregnant or lactating woman 6. Subject who needs long-term administration of drugs including immunosuppressive agents, agents related to high risk in the hepatic/renal toxicity, agents influencing renal excretion 7. History of liver transplantation or planned for liver transplantation 8. Subject who was diagnosed malignant tumor and has been receiving chemotherapy 9. Subject who has HCC history or who shows potential hepatocellular carcinoma (HCC) finding such as suspicious region in the radiologic exam(abdominal US or CT) or serum Alpha Feto Protein(AFP) elevation 10. Renal Insufficiency (CLcr < 50ml/min based on Cockcroft-Gault equation considering weight, ages and serum creatinine) 11. Subject who has a liver disease other than chronic hepatitis B (e.g. hemochromatosis, Wilson's disease, alcoholic liver disease, nonalcoholic fatty liver disease, alpha 1-antitrypsin deficiency etc.) 12. Subject who has a history of hypersensitivity to study drug or its ingredients 13. Subject who is involved in other clinical trial within 60 days prior to study entry 14. Subject who the investigator deems inappropriate to participate in this study

Additional Information

Official title A Randomized, Multicenter, Prospective Study to Compare Antiviral Efficacy and Safety of Switching to ETV Plus TDF Versus Maintaining LAM/LDT Plus ADF Combination in CHC With PVR to LAM/LDF Plus ADF Combination Rescue Therapy for YMDD Mutation
Principal investigator Sang Hoon Ahn, MD, PhD
Description 1. As TDF has not been approved yet in Korea, current KASL practice guideline generally recommends to add ADV in LAM-resistant or LdT-resistant patients. 2. However, several local literatures reported a substantial proportion of patients treated with LAM plus ADV combination therapy showed a persistently inadequate or partial virologic response('VR') and YMDDm still maintained in spite of under rescue combination therapy. 3. Due to the unavailability of TDF in Korea, ETV plus ADV combination has being considered a better salvage therapy with non-overlapping cross-resistance profiles in pts who fail to LAM plus ADV rescue therapy and local report demonstrated that the rate of VR was significantly higher with ETV+ADV switching group than LAM+ADV continuation group in partial responder to LAM plus ADV combination rescue therapy for LAM resistance. 4. Hence, more earlier combination therapy with the most potent Nucleoside and Nucleotide analogue would be a promising salvage treatment for previous NA treatment failures but comparative prospective trials are limited. 5. Therefore, this study will investigate the greater effectiveness and safety of switching to the most potent combination versus maintaining LAM(or LdT) plus ADV and also compare the rate of VR based on the HBV DNA cut-off level at switching - more than and less than 20,000 IU/mL. All subjects will orally take assigned drugs once daily for 48 weeks. All subjects will be assessed at baseline and every three months thereafter. Evaluations at each visit will include vital signs, physical examinations, laboratory tests, HBV DNA levels and adverse events. At baseline and every six months thereafter, serum will be assayed for HBV serology. Genotypic analysis will be performed at baseline and 48 weeks.
Trial information was received from ClinicalTrials.gov and was last updated in January 2014.
Information provided to ClinicalTrials.gov by Yonsei University.