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Trial record 65 of 349 for:    hepatitis b | Open Studies

A Study of Pegylated Interferon Alfa-2A in Combination With Lamivudine or Entecavir Compared With Untreated Control Group in Children With Hepatitis B Envelope Antigen (HBeAg)-Positive Chronic Hepatitis B (CHB) in the Immune-Tolerant Phase

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2017 by Hoffmann-La Roche
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT02263079
First received: October 2, 2014
Last updated: January 19, 2017
Last verified: January 2017
  Purpose
This randomized, controlled, parallel group, open-label multicenter study will evaluate the efficacy and safety of a combination of pegylated interferon alfa-2A (Pegasys) plus lamivudine or entecavir compared with an untreated control group in participants with HBeAg positive CHB in the immune tolerant phase.

Condition Intervention Phase
Hepatitis B, Chronic
Drug: Entecavir
Drug: Lamivudine
Drug: Pegylated Interferon Alfa-2A
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Phase IIIb, Randomized, Open-Label Study of Pegylated Interferon Alfa-2A in Combination With Lamivudine or Entecavir Compared With Untreated Control Patients in Children With HBeAg Positive Chronic Hepatitis B in the Immune-Tolerant Phase

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Proportion of Participants With Loss of Hepatitis B Surface Antigen (HBsAg) at 24 Weeks Post-End of Treatment/End of Untreated Observation [ Time Frame: 24 weeks post-end of treatment /end of untreated observation (Week 80) ]

Secondary Outcome Measures:
  • Proportion of Participants With Loss of HBsAg [ Time Frame: 1, 2, 3, 4, and 5 years post-end of treatment (End of treatment = Week 56) ]
  • Proportion of Participants With Loss of Hepatitis B Virus Envelope Antigen (HBeAg) [ Time Frame: 24 weeks post-end of treatment /end of untreated observation (Week 80), 1, 2, 3, 4, and 5 years post-end of treatment ]
  • Proportion of Participants With Seroconversion to Hepatitis B Surface Antibody (Anti-HBs), Defined as Loss of HBsAg and Presence of anti-HBs [ Time Frame: 24 weeks post-end of treatment /end of untreated observation (Week 80), 1, 2, 3, 4, and 5 years post-end of treatment (End of treatment = Week 56) ]
  • Proportion of Participants With Seroconversion to Hepatitis B Envelope Antibody (Anti-Hbe), Defined as Loss of HBeAg and Presence of anti-Hbe [ Time Frame: 24 weeks post-end of treatment /end of untreated observation (Week 80), 1, 2, 3, 4, and 5 years post-end of treatment (End of treatment = Week 56) ]
  • Proportion of Participants With Different Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels (Less Than [<] 20,000 International Units per Milliliter [IU/mL], < 2000 IU/mL, or Undetectable HBV DNA) [ Time Frame: 24 weeks post-end of treatment /end of untreated observation (Week 80), 1, 2, 3, 4, and 5 years post-end of treatment (End of treatment = Week 56) ]
  • Change From Baseline in HBV DNA Levels [ Time Frame: Baseline, 24 weeks post-end of treatment /end of untreated observation (Week 80), 1, 2, 3, 4, and 5 years post-end of treatment (End of treatment = Week 56) ]
  • Proportion of Participants With Combined Response for HBeAg Seroconversion (Defined as Loss of HBeAg and Presence of anti-HBe) and HBV DNA Levels <20,000 IU/mL [ Time Frame: 24 weeks post-end of treatment /end of untreated observation (Week 80), 1, 2, 3, 4, and 5 years post-end of treatment (End of treatment = Week 56) ]
  • Proportion of Participants With Combined Response for HBeAg Seroconversion (Defined as Loss of HBeAg and Presence of anti-HBe) and HBV DNA Levels <2000 IU/mL [ Time Frame: 24 weeks post-end of treatment /end of untreated observation (Week 80), 1, 2, 3, 4, and 5 years post-end of treatment (End of treatment = Week 56) ]
  • Proportion of Participants With Adverse Events [ Time Frame: Baseline up to 5 years after end of treatment (End of Treatment = Week 56) ]
  • Maximum Serum Plasma Concentration (Cmax) of Pegylated Interferon-Alfa-2A (Peg-IFN-Alfa-2A) [ Time Frame: Pre-lamivudine/entecavir dose (-6 hours [Hr] to Hr 0) on baseline (Study Day 1); Pre-Peg-IFN-Alfa-2A dose (-6 Hr to Hr 0) on Day 1 of Weeks 20, 32, & 56; 24-48, 72-96, & 168 Hr post-Peg-IFN-Alfa-2A dose on Day 1 of Week 32; at Day 1 of Week 60 ]
  • Area Under the Concentration-Time Curve (AUC) of Peg-IFN-Alfa-2A [ Time Frame: Pre-lamivudine/entecavir dose (-6 Hr to Hr 0) on baseline (Study Day 1); Pre-Peg-IFN-Alfa-2A dose (-6 Hr to Hr 0) on Day 1 of Weeks 20, 32, & 56; 24-48, 72-96, & 168 Hr post-Peg-IFN-Alfa-2A dose on Day 1 of Week 32; at Day 1 of Week 60 ]
  • Clearance (CL/F) of Peg-IFN-Alfa-2A [ Time Frame: Pre-lamivudine/entecavir dose (-6 Hr to Hr 0) on baseline (Study Day 1); Pre-Peg-IFN-Alfa-2A dose (-6 Hr to Hr 0) on Day 1 of Weeks 20, 32, & 56; 24-48, 72-96, & 168 Hr post-Peg-IFN-Alfa-2A dose on Day 1 of Week 32; at Day 1 of Week 60 ]
  • Volume of Distribution (V/F) of Peg-IFN-Alfa-2A [ Time Frame: Pre-lamivudine/entecavir dose (-6 Hr to Hr 0) on baseline (Study Day 1); Pre-Peg-IFN-Alfa-2A dose (-6 Hr to Hr 0) on Day 1 of Weeks 20, 32, & 56; 24-48, 72-96, & 168 Hr post-Peg-IFN-Alfa-2A dose on Day 1 of Week 32; at Day 1 of Week 60 ]
  • Percentage of Participants by Tanner Stage [ Time Frame: Baseline up to 5 years after end of treatment (End of Treatment = Week 56) ]

Estimated Enrollment: 114
Study Start Date: June 2014
Estimated Study Completion Date: April 2024
Estimated Primary Completion Date: October 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Peg-IFN-Alfa-2A + Lamivudine or Entecavir
Participants will receive lamivudine or entecavir alone for 8 weeks followed by peg-IFN-alfa-2A in combination with lamivudine or entecavir for 48 weeks.
Drug: Entecavir
Participants will receive entecavir, either as a film-coated tablet or oral solution, once daily at a dose of 0.015 milligrams per kilogram (mg/kg) (maximum daily dose of 0.5 mg).
Drug: Lamivudine
Participants will receive lamivudine, either as a film-coated tablet or oral solution, once daily at a dose of 3 mg/kg (maximum daily dose of 100 mg).
Drug: Pegylated Interferon Alfa-2A
Participants will receive pegylated interferon-alfa-2A at a body surface area (BSA) based dose of 180 micrograms per 1.73 square meter (mcg/1.73m^2) BSA.
Other Name: Pegasys, Peg-IFN-Alfa-2A
No Intervention: Untreated Control Participants
Untreated control participants will be observed up to 80 weeks.

  Eligibility

Ages Eligible for Study:   3 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Positive for HBsAg and HBeAg for more than 6 months prior to baseline
  • Detectable HBV-DNA (>20,000 IU/mL) as measured by polymerization chain reaction (PCR) or hybridization on at least 2 occasions at least one month apart with the latest determination obtained less than or equal to (</=) 42 days prior to baseline
  • Compensated liver disease (Child-Pugh Class A clinical classification)
  • Either Liver biopsy performed within 2 years prior to baseline showing no or minimal fibrosis (Liver Biopsy Scores and stable normal ALT levels (less than or equal to upper limit of normal [ULN]) during the 6 months leading up to baseline (including two separate occasions at least 1 month apart over the 6 months prior to baseline). Screening ALT levels must be normal (</= ULN) OR Stable normal ALT levels (</= ULN), during the 1 year leading up to baseline (including three separate occasions at least 1 month apart over the 1 year prior to baseline) and no signs of hepatocellular carcinoma (HCC), advanced fibrosis/cirrhosis, or splenomegaly on liver abdominal ultrasound at screening. Screening ALT levels must be normal (</= ULN)

Exclusion Criteria:

  • Participants who have received investigational drugs or licensed treatments with anti HBV activity (Exception: Participants who have had a limited [</= 7-day] course of acyclovir for herpetic lesions more than 1 month before the study baseline visit are not excluded)
  • Participants who have participated in any other clinical trial or who have received any investigational drug within 6 months prior to baseline
  • Known hypersensitivity to interferon (IFN), pegylated interferon-alfa-2a or lamivudine or entecavir
  • Positive test results at screening for hepatitis A virus Immunoglobulin M (IgM) antibody (Ab), anti-hepatitis C virus (HCV) Ab, anti- hepatitis D (HDV) Ab or anti-human immunodeficiency virus (HIV) Ab
  • Decompensated liver disease (e.g., Child-Pugh Class B or C clinical classification or clinical evidence such as ascites or varices)
  • Advanced fibrosis or cirrhosis
  • Suspicion of HCC on liver abdominal ultrasound (all patients to have liver abdominal ultrasound within 6 months prior to baseline)
  • History or other evidence of a medical condition associated with chronic liver disease other than CHB including metabolic liver diseases such as hemochromatosis, Wilson's disease or alpha-1 anti-trypsin deficiency
  • Active substance abuse within 6 months prior to screening
  • Sexually active females of childbearing potential and sexually active males who are not willing to utilize reliable contraception during treatment and for 90 days following the end of treatment
  • Females who are pregnant or who are breastfeeding (females of childbearing potential who have a positive urine or serum pregnancy test result within 24 hours of baseline are excluded)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02263079

Contacts
Contact: Reference Study ID Number: NV25361 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global.rochegenentechtrials@roche.com

  Show 48 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02263079     History of Changes
Other Study ID Numbers: NV25361  2006-000977-31 
Study First Received: October 2, 2014
Last Updated: January 19, 2017

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis, Chronic
Hepatitis B
Hepatitis B, Chronic
Hepatitis, Viral, Human
Liver Diseases
Digestive System Diseases
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Interferons
Interferon-alpha
Lamivudine
Peginterferon alfa-2a
Entecavir
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunologic Factors
Physiological Effects of Drugs
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-HIV Agents

ClinicalTrials.gov processed this record on February 20, 2017