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

NCT ID: NCT02263079

Last Updated: 2020-08-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 62 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-06-16
• Study Completion Date: 2020-01-29

Brief Summary

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. NOTE: STUDY RECRUITMENT HAS BEEN TERMINATED

Conditions

Pediatric Immuno-Tolerant Chronic Hepatitis B

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Entecavir

Intervention Type: DRUG

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).

Lamivudine

Intervention Type: DRUG

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).

Pegylated Interferon Alfa-2A

Intervention Type: DRUG

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.

Untreated Control Participants

Untreated control participants will be observed up to 80 weeks.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Peg-INF-Alfa-2A Monotherapy

Participants will receive Peginterferon Alfa 2A subcutaneously once weekly with dosing based on body surface area (BSA) categories for 48 weeks.

Group Type: EXPERIMENTAL

Pegylated Interferon Alfa-2A

Intervention Type: DRUG

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.

Interventions

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).

Intervention Type: 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).

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Pegasys, Peg-IFN-Alfa-2A

Eligibility 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)

• Minimum Eligible Age: 3 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Children's Mercy Hosp Clinics

Kansas City, Missouri, United States

Columbia University

New York, New York, United States

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Womens and Childrens Hospital; Department of Gastroenterology

North Adelaide, South Australia, Australia

Cliniques Universitaires St-Luc

Brussels, , Belgium

UZ Gent

Ghent, , Belgium

Universitätsklinikum Essen; Klinik für Kinder- und Jugendmedizin Pädiatrie II

Essen, , Germany

Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Zentrum für Kinder- und Jugendmedizin

Mainz, , Germany

Dr. von Haunerschen Kinderspital, Kinderchirurgische Klinik und Poliklinik

München, , Germany

HELIOS Klinikum Wuppertal, Zentrum für Kinder- und Jugendmedizin, Universität Witten-Herdecke

Wuppertal, , Germany

Azienda Ospedaliero-Universitaria Policlinico S. Orsola Malpighi; U.O. Malattie Infettive

Bologna, Emilia-Romagna, Italy

University Malaya Medical Center; Department of Paediatrics

Kuala Lumpur, , Malaysia

Grigore Alexandrescu Emergency Clinical Hospital for Children

Bucharest, , Romania

FSI Scientific research Institute of children's infections

Saint Petersburg, , Russia

MC Gepatolog

Samara, , Russia

Chang-Gung Memorial Hospital-Linkou; Division of Pediatric Gastroenterology, Dept Pediatrics

Taoyuan, , Taiwan

Cukurova University Medical School Department of Pediatrics; Pediatric Infectious Diseases

Adana, , Turkey (Türkiye)

Ankara University School of Medicine, Pediatrics Department; Pediatric Gastroenterology

Ankara, , Turkey (Türkiye)

Hacettepe Uni , School of Medicine; Gastroenterology

Ankara, , Turkey (Türkiye)

Gazi Universitesi Tip Fakultesi Pediyatri Anabilim Dalı; Pediyatrik Gastroenteroloji

Ankara, , Turkey (Türkiye)

SI Institute of the pediatrics, obstetrics and gynecology

Kyiv, , Ukraine

Birmingham Children'S Hopsital; Liver Unit

Birmingham, , United Kingdom

Leeds Teaching Hospitals NHS Trust

Leeds, , United Kingdom

Kings College Hospital NHS Foundation Trust

London, , United Kingdom

North Manchester General Hospital

Manchester, , United Kingdom

Countries

United States; Australia; Belgium; Germany; Italy; Malaysia; Romania; Russia; Taiwan; Turkey (Türkiye); Ukraine; United Kingdom

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2006-000977-31

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

NV25361

Identifier Type: -

Identifier Source: org_study_id