Clinical trial NCT00412750: Efficacy and Safety of Telbivudine in Treatment naïve Patients With Hepatitis B e Antigen (HBeAg)-Positive Chronic Hepatitis B (CHB)
Official title: A Randomized, Open-label, Controlled, Multi-center Two-year Study Comparing Efficacy and Safety of Telbivudine, 600 mg PO in Combination With Peginterferon Alpha-2a sq 180 µg With Peginterferon Alpha-2a Monotherapy, and With Telbivudine Monotherapy in Treatment naïve Patients With HBeAg-positive CHB.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Hepatitis B
Keywords: hepatitis B
hepatitis B Virus (HBV)
chronic hepatitis B
telbivudine
peginterferon
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2006-12-18
Enrollment: 159
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To evaluate the combination of telbivudine 600 mg orally (PO) once daily and peginterferon alpha-2a 180 ug subcutaneous (sq) injection weekly for antiviral efficacy in comparison to peginterferon alpha-2a monotherapy.


Eligibility criteria: Inclusion Criteria:

Documented Chronic hepatitis B (CHB) defined by all of the following:

* Clinical history compatible with CHB
* Detectable serum Hepatitis B Surface Antigen (HBsAg) at the Screening visit and at least 6 months prior
* HBeAg-positive at the Screening visit
* Hepatitis B 'e' Antibody (HBeAb)-negative at the Screening visit
* History of evidence of chronic liver inflammation,
* Elevated serum Alanine aminotransferase (ALT) level (1.3 - 10 x upper limit of normal (ULN)) at the Screening visit
* Serum HBV DNA level ≥ 6 log10 copies/mL,
* Chronic liver inflammation on previous liver biopsy within the previous 24 months.

Exclusion Criteria:

* Co-infection with Hepatitis C Virus (HCV), Hepatitis D Virus (HDV), or Human Immunodeficiency Virus (HIV).
* 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 methadone.
* 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.
  * History of clinical and laboratory evidence of chronic pancreatitis, or demonstrates a clinical and laboratory course consistent with current pancreatitis.
* Has laboratory values during screening visit not within normal limits.
* Is pregnant or breastfeeding.
* Is a women of child-bearing potential that is unwilling to practice birth control.

Primary outcomes:
measure: Percentage of Participants Who Achieved HBV DNA Non-detectability With Peginterferon Alpha-2a Plus Telbivudine Combination Therapy Versus Peginterferon Alpha-2a Monotherapy
timeFrame: At week 52
measure: Percentage of Participants With HBV DNA Non-detectability and Alanine Aminotransferase (ALT) Normalization at Week 12 and Week 24 in Participants With HBeAg-positive Chronic Hepatitis B (CHB)
timeFrame: Weeks 12 and 24
Secondary outcomes:
measure: Change From Baseline in HBV DNA Concentration
timeFrame: Weeks 12 and 24
measure: Percentage of Participants Who Experienced Virologic Breakthrough at Weeks 48 and 52
timeFrame: Weeks 48 and 52
measure: Percentage of Participants With Hepatitis B 'e' Antigen (HBeAg) Loss and HBeAg Seroconversion
timeFrame: Weeks 18, 24, 48, 52 and Treatment completion (TC)
measure: Percentage of Participants Who Achieved HBV DNA Non-detectability With Telbivudine Monotherapy Versus Peginterferon Alpha-2a Monotherapy
timeFrame: Week 52
measure: Percentage of Participants Who Achieved HBV DNA Non-detectability With Peginterferon Alpha-2a Plus Telbivudine Combination Therapy Versus Telbivudine Monotherapy
timeFrame: Week 52
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: Novartis
state: California
Study officials:
References:
citation: Marcellin P, Wursthorn K, Wedemeyer H, Chuang WL, Lau G, Avila C, Peng CY, Gane E, Lim SG, Fainboim H, Foster GR, Safadi R, Rizzetto M, Manns M, Bao W, Trylesinski A, Naoumov N. Telbivudine plus pegylated interferon alfa-2a in a randomized study in chronic hepatitis B is associated with an unexpected high rate of peripheral neuropathy. J Hepatol. 2015 Jan;62(1):41-7. doi: 10.1016/j.jhep.2014.08.021. Epub 2014 Aug 23.