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

NCT02263079 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: NV253612006-000977-31
• Study Type: interventional
• Target: 62
• Locations: 12 countries
• Sites: 25

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

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Loss of Hepatitis B Surface Antigen (HBsAg) at 24 Weeks Post-End of Treatment/End of Untreated Observation

  This endpoint is defined as loss of HBsAg at 24 weeks post-treatment (follow-up Week 24)/end of untreated observation (Week 80). The percentage of responders (response rate) and 95% CI (using the Clopper-Pearson method) for the response rate are presented for each group.

  24 weeks post-treatment/at the end of untreated observation (Week 80)

Secondary Outcomes (12)

• Percentage of Participants With Loss of HBsAg

  1 year post-end of treatment (End of treatment = Week 56)

• Percentage of Participants With Loss of Hepatitis B Virus Envelope Antigen (HBeAg)

  24 weeks post-treatment /end of untreated observation (Week 80), and 1 year post-end of treatment (End of treatment = Week 56)

• Percentage of Participants With Seroconversion to Hepatitis B Surface Antibody (Anti-HBs), Defined as Loss of HBsAg and Presence of Anti-HBs

  24 weeks post-treatment /end of untreated observation (Week 80), and 1 year post-end of treatment (End of treatment = Week 56)

• Percentage of Participants With Seroconversion to Hepatitis B Envelope Antibody (Anti-HBe), Defined as Loss of HBeAg and Presence of Anti-HBe

  24 weeks post-treatment /end of untreated observation (Week 80), and 1 year post-end of treatment (End of treatment = Week 56)

• Percentage 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)

  24 weeks post-treatment /end of untreated observation (Week 80), and 1 year post-end of treatment (End of treatment = Week 56)

Study Arms (3)

Peg-IFN-Alfa-2A + Lamivudine or Entecavir

EXPERIMENTAL

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; Drug: Lamivudine; Drug: Pegylated Interferon Alfa-2A

Untreated Control Participants

NO INTERVENTION

Untreated control participants will be observed up to 80 weeks.

Peg-INF-Alfa-2A Monotherapy

EXPERIMENTAL

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

Drug: Pegylated Interferon Alfa-2A

Interventions

Entecavir 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).

Peg-IFN-Alfa-2A + Lamivudine or Entecavir

Lamivudine 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).

Peg-IFN-Alfa-2A + Lamivudine or Entecavir

Pegylated Interferon Alfa-2A 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.

Also known as: Pegasys, Peg-IFN-Alfa-2A

Peg-IFN-Alfa-2A + Lamivudine or Entecavir; Peg-INF-Alfa-2A Monotherapy

Eligibility Criteria

• Age: 3 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (25)

Children's Mercy Hosp Clinics

Kansas City, Missouri, 64108, United States

Location

Columbia University

New York, New York, 10032-3725, United States

Location

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Womens and Childrens Hospital; Department of Gastroenterology

North Adelaide, South Australia, 5006, Australia

Location

Cliniques Universitaires St-Luc

Brussels, 1200, Belgium

Location

UZ Gent

Ghent, 9000, Belgium

Location

Universitätsklinikum Essen; Klinik für Kinder- und Jugendmedizin Pädiatrie II

Essen, 45122, Germany

Location

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

Mainz, 55131, Germany

Location

Dr. von Haunerschen Kinderspital, Kinderchirurgische Klinik und Poliklinik

München, 80337, Germany

Location

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

Wuppertal, 42283, Germany

Location

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

Bologna, Emilia-Romagna, 40138, Italy

Location

University Malaya Medical Center; Department of Paediatrics

Kuala Lumpur, 59100, Malaysia

Location

Grigore Alexandrescu Emergency Clinical Hospital for Children

Bucharest, 011743, Romania

Location

FSI Scientific research Institute of children's infections

Saint Petersburg, 197022, Russia

Location

MC Gepatolog

Samara, 443100, Russia

Location

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

Taoyuan, 333, Taiwan

Location

Cukurova University Medical School Department of Pediatrics; Pediatric Infectious Diseases

Adana, 01330, Turkey (Türkiye)

Location

Ankara University School of Medicine, Pediatrics Department; Pediatric Gastroenterology

Ankara, 06100, Turkey (Türkiye)

Location

Hacettepe Uni , School of Medicine; Gastroenterology

Ankara, 06100, Turkey (Türkiye)

Location

Gazi Universitesi Tip Fakultesi Pediyatri Anabilim Dalı; Pediyatrik Gastroenteroloji

Ankara, 06500, Turkey (Türkiye)

Location

SI Institute of the pediatrics, obstetrics and gynecology

Kyiv, 04050, Ukraine

Location

Birmingham Children'S Hopsital; Liver Unit

Birmingham, B4 6NH, United Kingdom

Location

Leeds Teaching Hospitals NHS Trust

Leeds, LS9 7AU, United Kingdom

Location

Kings College Hospital NHS Foundation Trust

London, SE5 9RS, United Kingdom

Location

North Manchester General Hospital

Manchester, M8 5RB, United Kingdom

Location

MeSH Terms

Interventions

entecavir; Lamivudine; peginterferon alfa-2a

Intervention Hierarchy (Ancestors)

Zalcitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Dideoxynucleosides

Limitations and Caveats

In accordance with the recommendation from the DSMB, enrollment was stopped due to low efficacy and a changed benefit risk assessment. Enrolled participants were allowed to complete treatment and were followed up for 1 year after the end of treatment

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

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
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 2, 2014
• First Posted: October 13, 2014
• Study Start: June 16, 2014
• Primary Completion: January 29, 2020
• Study Completion: January 29, 2020
• Last Updated: August 24, 2020
• Results First Posted: August 24, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will share

Locations

RU (2); UA (1); BE (2); MY (1); IT (1); US (3); DE (4); TW (1); GB (4); RO (1); AU (1); TU (4)