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

NCT00412750 | Terminated Phase 3 Results

• 1 other identifier: CLDT600A2406
• Study Type: interventional
• Target: 159
• Locations: 1 country
• Sites: 1

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.

Conditions

Hepatitis B

Keywords

hepatitis B; hepatitis B Virus (HBV); chronic hepatitis B; telbivudine; peginterferon

Outcome Measures

Primary Outcomes (2)

• 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

• 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

Secondary Outcomes (5)

• Change From Baseline in HBV DNA Concentration

  Weeks 12 and 24

• Percentage of Participants Who Experienced Virologic Breakthrough at Weeks 48 and 52

  Weeks 48 and 52

• Percentage of Participants With Hepatitis B 'e' Antigen (HBeAg) Loss and HBeAg Seroconversion

  Weeks 18, 24, 48, 52 and Treatment completion (TC)

• Percentage of Participants Who Achieved HBV DNA Non-detectability With Telbivudine Monotherapy Versus Peginterferon Alpha-2a Monotherapy

  Week 52

• Percentage of Participants Who Achieved HBV DNA Non-detectability With Peginterferon Alpha-2a Plus Telbivudine Combination Therapy Versus Telbivudine Monotherapy

  Week 52

Study Arms (3)

LdT+ PEG-INF

EXPERIMENTAL

Telbivudine (LdT) 600 mg orally once a day for 104 weeks in combination with peginterferon alpha-2a (PEG-INF)180 μg subcutaneous injection once a week for 52 weeks.

Drug: Telbivudine (LdT); Drug: peginterferon alpha-2a

LdT Monotherapy

EXPERIMENTAL

Telbivudine (LdT) monotherapy: 600 mg orally once daily for 104 weeks.

Drug: Telbivudine (LdT)

PEG-INF Monotherapy

ACTIVE COMPARATOR

Peginterferon alpha-2a (PEG- INF) monotherapy: 180 μg subcutaneous injection once a week for 52 weeks.

Drug: peginterferon alpha-2a

Interventions

Telbivudine (LdT) DRUG

600 mg orally once daily for 104 weeks.

Also known as: Sebivo

LdT Monotherapy; LdT+ PEG-INF

peginterferon alpha-2a DRUG

180 μg subcutaneous injection once a week for 52 weeks.

Also known as: Pegasys

LdT+ PEG-INF; PEG-INF Monotherapy

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis: lead

Study Sites (1)

Novartis

San Francisco, California, 94115, United States

Location

Related Publications (1)

• 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.

  PMID: 25152207 DERIVED

MeSH Terms

Conditions

Hepatitis B; Hepatitis B, Chronic

Interventions

Telbivudine; peginterferon alfa-2a

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis; Liver Diseases; Digestive System Diseases; Hepatitis, Chronic; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thymidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: December 15, 2006
• First Posted: December 18, 2006
• Study Start: December 1, 2006
• Primary Completion: February 1, 2009
• Study Completion: February 1, 2009
• Last Updated: July 13, 2011
• Results First Posted: July 13, 2011

Record last verified: 2011-06

Locations

US (1)