Efficacy and Safety of Telbivudine in Treatment naïve Patients With Hepatitis B e Antigen (HBeAg)-Positive Chronic Hepatitis B (CHB)

Hepatitis B Clinical Trial

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.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00412750
• Other study ID #: CLDT600A2406
• Status: Terminated
• Phase: Phase 3
• First received: December 15, 2006
• Last updated: June 14, 2011
• Start date: December 2006
• Est. completion date: February 2009

Study information

• Verified date: June 2011
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationAustralia: Department of Health and Ageing Therapeutic Goods AdministrationBelgium: The Federal Public Service (FPS) Health, Food Chain Safety and EnvironmentFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Federal Institute for Drugs and Medical DevicesItaly: Ministry of HealthNetherlands: Medicines Evaluation Board (MEB)Spain: Ministry of Health and ConsumptionSwitzerland: Federal Office of Public HealthUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyIsrael: Ministry of HealthArgentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia MedicaTaiwan: National Bureau of Controlled DrugsSingapore: Health Sciences AuthorityNew Zealand: Health and Disability Ethics CommitteesHong Kong: Department of Health
• Study type: Interventional

Clinical Trial 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.

Other known NCT identifiers

• NCT00376389

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 159
• Est. completion date: February 2009
• Est. primary completion date: February 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic

Intervention

Drug:
• Telbivudine (LdT)
600 mg orally once daily for 104 weeks.
• peginterferon alpha-2a
180 µg subcutaneous injection once a week for 52 weeks.

Locations

Country	Name	City	State
United States	Novartis	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Novartis

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Who Achieved HBV DNA Non-detectability With Peginterferon Alpha-2a Plus Telbivudine Combination Therapy Versus Peginterferon Alpha-2a Monotherapy	The original primary efficacy variable was the percentage of patients achieving HBV DNA non-detectability utilizing polymerase chain reaction (PCR) (threshold for detection 300 copies/mL); however, this analysis was not performed due to premature study termination.	At week 52	No
Primary	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)	The percentage of participants who achieved HBV DNA non-detectability using the COBAS Amplicor HBV Monitor assay utilizing polymerase chain reaction (PCR) (threshold for detection 300 copies/mL) and Alanine aminotransferase (ALT) normalization defined as ALT within normal limits on two successive visits for a patient with an elevated ALT (>1.0 x upper limit normal) at baseline summarized at Weeks 12 and 24.	Weeks 12 and 24	No
Secondary	Change From Baseline in HBV DNA Concentration	The change from baseline in HBV DNA concentration at Weeks 12 and 24 was analyzed using an analysis of covariance (ANCOVA) model with baseline HBV DNA concentration (log10 copies/ml) as a covariate, treatment and country as factors.	Weeks 12 and 24	No
Secondary	Percentage of Participants Who Experienced Virologic Breakthrough at Weeks 48 and 52	The percentage of participants with Virologic breakthrough at Week 48 and 52 by treatment. For the subgroup of patients on treatment who achieve HBV DNA >= 1 log10 copies/mL reduction from baseline on 2 consecutive visits, Virologic Breakthrough is defined as HBV DNA >= 1 log10 copies/mL from nadir on two consecutive visits.	Weeks 48 and 52	No
Secondary	Percentage of Participants With Hepatitis B 'e' Antigen (HBeAg) Loss and HBeAg Seroconversion	HBeAg loss is defined as the loss of detectable serum HBeAg in a patient who was HBeAg positive at baseline. HBeAg seroconversion is defined as HBeAg loss with detectable Hepatitis B 'e' antibody (HBeAb). The efficacy was assessed for 18 weeks, 24 weeks, 48 weeks, 52 weeks and on treatment completion (TC).	Weeks 18, 24, 48, 52 and Treatment completion (TC)	No
Secondary	Percentage of Participants Who Achieved HBV DNA Non-detectability With Telbivudine Monotherapy Versus Peginterferon Alpha-2a Monotherapy	Antiviral efficacy was assessed by percentage of patients achieving HBV DNA non-detectability assay utilizing polymerase chain reaction (PCR) (threshold for detection 300 copies/mL); however, this analysis was not performed due to premature study termination.	Week 52	No
Secondary	Percentage of Participants Who Achieved HBV DNA Non-detectability With Peginterferon Alpha-2a Plus Telbivudine Combination Therapy Versus Telbivudine Monotherapy	Antiviral efficacy was assessed by percentage of patients achieving HBV DNA non-detectability assay utilizing polymerase chain reaction (PCR) (threshold for detection 300 copies/mL); however, this analysis was not performed due to premature study termination.	Week 52	No