Treatment of naïve patients with HBeAg-positive compensated chronic hepatitis B MedDRA version: 8.1 Level: LLT Classification code 10008910 Term: Chronic hepatitis B
Conditions
Interventions
Product Name: Telbivudine
Product Code: LdT, LdT600
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: telbivudine
CAS Number:
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female, at least 18 years of age. 2. Documented CHB defined by all of the following: • Clinical history compatible with CHB • Detectable serum HBsAg at the Screening visit and at least 6 months prior • HBeAg-positive at the Screening visit • HBeAb-negative at the Screening visit • History of evidence of chronic liver inflammation, documented by previous history of elevated serum ALT (at least two elevated ALT values spanning six months or more, documented in available records) • Elevated serum ALT level (1.3 – 10 x upper limit of normal (ULN)) at the Screening visit • Serum HBV DNA level = 6 log10 copies/mL, as determined by the COBAS Amplicor HBV PCR assay at the central study laboratory at Screening visit • Chronic liver inflammation on previous liver biopsy within the previous 24 months in source documents. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes 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
Exclusion criteria: 1.Co-infection with HCV, HDV, or HIV. 2.Has any of the following drug therapy: •Previously been treated in a trial with telbivudine •Received nucleoside or nucleotide therapy whether approved or investigational. •Received any immunomodulatory treatment in the 12 months before Screening for this study. •Has a medical condition that required prolonged or frequent use of systemic acyclovir or famciclovir. Has a medical condition that requires frequent or prolonged use of systemic corticosteroids although inhaled or intra-articular corticosteroids are allowed. •Has a medical condition requiring the chronic or prolonged use of potentially hepatotoxic drugs or nephrotoxic drugs. •Is currently abusing alcohol or illicit drugs or has a history of alcohol abuse illicit substance abuse within the preceding two years. •Uses other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer. •Is currently receiving methodone. 4.Patient has any of the following: •History of or clinical signs/symptoms of hepatic decompensation such as ascites, esophageal variceal bleeding, hepatic encephalopathy, or spontaneous bacterial peritonitis. •History of malignancy of any organ system, treated or untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin. Patients with previous findings suggestive of possible HCC should have the disease ruled out prior to entrance into the study. •One or more additional known primary or secondary causes of liver disease other than hepatitis B, including steatohepatitis. Note: Gilbert's syndrome and Dubin-Johnson syndrome are not considered exclusion criteria for this study. •History of clinical and laboratory evidence of chronic pancreatitis, or demonstrates a clinical and laboratory course consistent with current pancreatitis. •Subject has a history of myopathy, myositis, or persistent muscle weakness. •Has in the opinion of the investigator 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. If in the opinion of the investigator, the patient is at risk of developing a serious or life-threatening neuropsychiatric condition • Pre-existing retinal disorder conditions. • Active autoimmune disorder, • Unstable angina, MI or CVA within the past three months 5.Has any of the following laboratory values during Screening: •HGB 1:320 •Prothrombin Time >3 seconds over ULN despite vitamin K administration •Patient has TSH < 0.35microU/ml or 5.5 microU/ml •Estimated calculated serum creatinine clearance < 50 mL/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to demonstrate the superior antiviral efficacy of the combination of peginterferon alpha-2a plus telbivudine vs peginterferon alpha-2a monotherapy as demonstrated by HBV DNA non-detectability using the COBAS Amplicor HBV Monitor™ assay (threshold for detection 300 copies/mL) at Week 52 in adult patients with HBeAg-positive CHB; Secondary Objective: The key secondary objectives of the study are •Demonstrate that telbivudine monotherapy has superior antiviral efficacy compared to peginterferon alpha-2a monotherapy as shown via PCR non-detectability at Week 52. •Compare the antiviral efficacy of the combination of peginterferon alpha-2a plus telbivudine to telbivudine monotherapy at Week 52 Other secondary objectives evaluated at various time points include: •Assessment HBV DNA non-detectability, reduction from baseline and sustained reduction in HBV DNA over the course of the study. •Assessment Virologic Breakthrough (See glossary of terms) and treatment emergent HBV resistance at Weeks 48 and 96 •Assessment of HBeAg loss and HBeAg seroconversion (defined as loss of HBeAg and development of HBeAb). •Assessment of HBsAg loss •Assessment of ALT normalization ;Primary end point(s): HBV DNA non-detectability at Week 52 | — |
Countries
Belgium, France, Germany, Italy, Netherlands, United Kingdom
Outcome results
None listed