A Randomized, Double-Blind Trial of Telbivudine (LdT) versus Lamivudine in Adults with Decompensated Chronic Hepatitis B and Evidence of Cirrhosis

• Conditions: Decompensated Chronic Hepatitis B and Evidence of Cirrhosis

• Registration Number: EUCTR2004-000443-17-LV
• Lead Sponsor: Idenix Pharmaceuticals, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2005-09-19
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 270

Inclusion Criteria

1. Male or female, 16 to 70 years of age.

2. Documented decompensated chronic hepatitis B defined by all of the following:
• Clinical history compatible with decompensated chronic hepatitis B related cirrhosis
• Child-Turcotte-Pugh score > 7 points.
• Evidence of hepatic cirrhosis or portal hypertension, documented by at least one of the following six methods:
i. Evidence of cirrhosis by previous liver biopsy within 5 years prior to Screen,
OR
ii. Evidence of cirrhosis by liver biopsy prior to randomization,
OR
iii. Evidence of cirrhosis by ultrasound, CT, or MRI imaging within 2 years prior to Screen,
OR
iv. Evidence of cirrhosis by ultrasound, CT, or MRI imaging prior to randomization (for patients who are considered high-risk for liver biopsy, due to thrombocytopenia or bleeding diatheses),
OR
v. Evidence of portal hypertension by previous endoscopy demonstrating moderate to severe esophageal varices protruding from esophagal or upper mucosal gastro-intestinal mucosa within 5 years prior to Screening,
OR
vi. Clinical evidence of portal hypertension documented by history of variceal bleeding, spontaneous bacterial peritonitis (SBP), endoscopic evidence of esophagal varices, or hepatic venous pressure gradient > 15 mmHg within 2 years prior to Screen
• Detectable serum HBsAg at the Screening visit
• Elevated serum ALT level (1.2 – 10 x ULN) at the Screening visit. If Screening ALT < 1.2xULN, re-test should be >1.2 x ULN or patient should have at least one documented ALT >1.2 x ULN in preceding 12 months.

3. Serum HBV DNA level = 5 log10 copies/mL, as determined by the PCR assay at the central study laboratory at Screen.

4. Patient is ambulatory.

5. Patient is willing and able to comply with the study drug regimen and all other study requirements.

6. The patient is willing and able to provide written informed consent to participate in the study.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Patient is pregnant or breastfeeding. Women of childbearing potential must have a
negative serum beta-human chorionic gonadotropin (ß-HCG) at Screening.

2. Patient is of childbearing potential (men and women) and unwilling to use double barrier method of contraception.

3. Patient is coinfected with hepatitis C virus (HCV), hepatitis D virus (HDV), or HIV.

4. Patient previously received more than 8 weeks of continuous lamivudine or
emtricitabine (FTC) treatment or more than 12 total weeks of lamivudine or
emtricitabine (FTC) treatment. If the patient previously received lamivudine or
emtricitabine (FTC) treatment, they must be off treatment for 8 weeks prior to the
Screening visit. A patient who is currently on lamivudine treatment should not be
discontinued from current treatment solely for the purpose of screening for this study.
Previous exposure to adefovir or other PMEA analogs (tenofovir, MCC-478), lobucavir,
entecavir, L-FMAU, L-Fd4C, or other investigational anti-HBV nucleosides/nucleotides
is allowed, but such antiviral treatment must have been discontinued at least 6 months prior to Screening.

5. Patient has received interferon or other immunomodulatory treatment for HBV infection in the 12 months before Screening for this study. Precluded therapies include, but are not limited to, interferon agents (alpha-, beta- or gamma-interferons), thymosin, IL-12, or other putative systemic immunomodulators.

6. Patient has a medical condition that requires prolonged or frequent use of systemic acyclovir or famciclovir

7. Patient is currently intubated or has an endotracheal tube for any reason, or requires chronic supplemental oxygen for any reason.

8. Patient has grade 3 or 4 encephalopathy as defined in Appendix 1 of the protocol.

9. Patient has history of acute variceal bleeding or SBP or bacterial sepsis within 8 weeks prior to Screening.

10. Patient has evidence of renal insufficiency defined as patient requires dialysis or has an estimated creatinine clearance, below 70 mL/min, as estimated by the Cockcroft-Gault formula:

11. Patient has a history of hepatocellular carcinoma (HCC) or findings suggestive of
possible HCC.

12. Patient has one or more additional known primary or secondary causes of liver disease.

13. Patient has a history of clinically-evident pancreatitis.

14. Patient is currently abusing alcohol or illicit drugs, or has a history of alcohol abuse or illicit substance abuse within the preceding two years.

15. Patient has a medical condition that requires frequent or prolonged use of systemic corticosteroids

16. Patient has been on warfarin or other anticoagulants within 30 days prior to Screening or if expected use during the present study.

17. Patient has any other concurrent medical or social condition likely to preclude
compliance with the schedule of evaluations in the protocol, or likely to confound the
efficacy or safety observations of the study, or has other medical or social circumstances likely to interfere with the schedule of evaluations.

18. Patient is enrolled or plans to enroll in another clinical trial of an investigational agent while participating in this study.

19. Patient has any of the following laboratory values at Screening:
• Hemoglobin < 9 g/dL for men or < 8 g/dL for women (< 90 g/L for men or < 80 g/L for women)
• Total WBC < 1,500/ mm3 (< 1.5 x 109/L)
• Absolute neutrophil count (ANC) < 1,000/mm3 (< 1.0x109/L)
• Platelet count < 30,000/mm3 (< 30 x 109/L)
• Serum al

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified