Entecavir/Pegylated Interferon in Immune Tolerant Children With Chronic Hepatitis B Virus (HBV) Infection

NCT01368497 | Completed Phase 3 Results DMC FDA Drug

• 10 other identifiers: DK082864 HBRN IT Peds TrialU01DK082916U01DK082864U01DK082874U01DK082944U01DK082843U01DK082871UL1TR000423UL1TR000004A-DK-3002-001
• Study Type: interventional
• Target: 60
• Locations: 2 countries
• Sites: 7

Brief Summary

The purpose of this study is to determine the safety and efficacy of treatment using a combination of drugs (entecavir and pegylated interferon) in children ages 3-\<18 years old with immunotolerant chronic hepatitis B.

Conditions

Hepatitis B

Keywords

Hepatitis B; HBV

Outcome Measures

Primary Outcomes (3)

• Proportion of Participants With Hepatitis B e Antigen (HBeAg) Loss & Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels ≤1,000 International Units (IU) Per Milliliter (mL)

  End of follow-up (up to 96 weeks)

• Incidence of Adverse Events (AEs) Per Person-Year

  The number of AEs includes both AEs and Serious Adverse Events (SAEs). The incidence is calculated as the number of AEs divided by the number of person-years of observation, which is the sum, across all participants, of the number of years between the start of treatment and the end of treatment, or the end of follow-up, respectively.

  From first treatment to the end of treatment (up to 48 weeks) and the end of follow-up (up to 96 weeks)

• Incidence of Serious Adverse Events (SAEs) Per Person-Year

  The incidence is calculated as the number of SAEs divided by the number of person-years of observation, which is the sum, across all participants, of the number of years between the start of treatment and the end of treatment, or the end of follow-up, respectively.

  From first treatment to the end of treatment (up to 48 weeks) and the end of follow-up (up to 96 weeks)

Secondary Outcomes (21)

• Proportion of Participants With Hepatitis B Surface Antigen (HBsAg) Loss

  End of treatment (up to 48 weeks)

• Proportion of Participants With Hepatitis B Surface Antigen (HBsAg) Loss

  End of follow-up (up to 96 weeks)

• Proportion of Participants With Hepatitis B e Antigen (HBeAg) Loss

  End of treatment (up to 48 weeks)

• Proportion of Participants With Hepatitis B e Antigen (HBeAg) Loss

  End of follow-up (up to 96 weeks)

• Proportion of Participants With HBeAg Seroconversion

  End of treatment (up to 48 weeks)

Study Arms (1)

Entecavir and peginterferon

EXPERIMENTAL

Entecavir for 8 weeks followed by 40 weeks of both entecavir and peginterferon

Drug: Entecavir and peginterferon

Interventions

Entecavir and peginterferon DRUG

Entecavir 0.015 mg/kg/day (up to 0.5 mg maximum daily dose) once daily for 48 weeks and Peginterferon alfa-2a 180 µg/1.73m2 subcutaneously once weekly for 40 weeks beginning 8 weeks after entecavir monotherapy).

Also known as: PEGASYS, peginterferon alfa 2a, Baraclude

Entecavir and peginterferon

Eligibility Criteria

• Age: 3 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Enrolled in \& completed the baseline evaluation in NCT01263600 OR completed necessary components of NCT01263600 baseline evaluation by the end of the baseline visit.
• to \<18 years at time of randomization (day 0).
• Documented chronic Hepatitis B virus (HBV) infection as evidenced by detection of hepatitis B surface antigen (HBsAg) in serum for ≥ 24 weeks prior to baseline OR positive HBsAg and negative anti-Hepatitis B core (HBc) immunoglobulin (IgM) within 24 weeks of baseline visit.
• Presence of hepatitis B e-antigen (HBeAg) in serum at the last screening visit within 6 weeks of baseline visit.
• Serum HBV DNA level \>10\^7 IU/mL on at least 2 occasions at least 12 weeks apart during the 52 weeks before baseline visit. The HBV DNA levels must be within 6 weeks of baseline visit.
• ALT ≤60 U/l in males or ≤40 U/l in females, measured on at least 2 occasions, at screening (within 6 weeks prior to baseline visit) \& at least 12 weeks prior to the screening visit \& within the 52 weeks prior to baseline visit.
• Compensated liver disease, with normal total bilirubin (except if Gilbert's syndrome), direct bilirubin ≤0.5 mg/dL, International Normalized Ratio (INR) ≤1.5, and serum albumin ≥3.5 g/dL.
• Creatinine clearance 90 ml/min.
• Absence of hepatocellular carcinoma on liver ultrasound in the past 48 weeks.

You may not qualify if:

• Presence of infection with Hepatitis C virus (HCV)-RNA or anti-HCV, anti-Hepatitis D virus (HDV), or HIV at screening.
• Presence of another cause of liver disease or hepatocellular cancer (HCC) (serum alpha-fetoprotein \>50ng /ml).
• Evidence of decompensated liver disease (Childs B-C).
• History or other evidence of a medical condition associated with chronic liver disease (e.g., hemochromatosis, autoimmune hepatitis, alcoholic liver disease, toxin exposures).
• Females who are pregnant or breastfeeding.
• Adolescent females unwilling or unable to use an acceptable method of contraception if sexually active during the treatment period.
• Children currently breastfeeding while their mother is taking lamivudine, or those who were exposed to lamivudine for ≥24 weeks via maternal lamivudine treatment during pregnancy and/or while breastfeeding.
• Previous liver or other organ transplantation including engrafted bone marrow transplant.
• Hematological abnormalities during the screening period that contraindicate full dosing with study drugs, e.g absolute neutrophil count \< 1.5 x 10\^9 cells/L or platelet count \< 120 x 10\^9 cells/L.
• Known allergy to study drugs; peginterferon alfa-2a or entecavir.
• Treatment with systemic acyclovir or famciclovir within the previous 6 months.
• Need for ongoing use of any antivirals with activity against HBV during the course of the study or history of receiving treatment for HBV.
• Any use of illegal drugs OR use of alcoholic beverages which in the opinion of a study physician is sufficient to prevent adequate compliance with study procedures or increase the risk of pancreatitis or hepatotoxicity.
• History of immunologically mediated disease (e.g. inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune haemolytic anemia, scleroderma, severe psoriasis, rheumatoid arthritis).
• History or other evidence of bleeding from esophageal varices or consistent with decompensated liver disease.

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): lead

Study Sites (7)

University of California San Francisco Medical Center

San Francisco, California, 94143, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Saint Louis Children's Medical Center

St Louis, Missouri, 63104, United States

Location

University of Texas Southwestern

Dallas, Texas, 75235, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98015, United States

Location

Hospital of Sick Children

Toronto, Ontario, m5g1x8, Canada

Location

Related Publications (1)

• Morris NM, Udry JR. Validation of a self-administered instrument to assess stage of adolescent development. J Youth Adolesc. 1980 Jun;9(3):271-80. doi: 10.1007/BF02088471.

  PMID: 24318082 BACKGROUND

Related Links

• Click here for more information about the Hepatitis B Research Network

MeSH Terms

Conditions

Hepatitis B

Interventions

entecavir; 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

Results Point of Contact

• Title: Dr. Steven Belle
• Organization: University of Pittsburgh

belle@edc.pitt.edu

412-624-3758

Study Officials

• Averell Sherker, MD

  National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

  STUDY CHAIR

• Ed Doo, MD

  National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

  STUDY CHAIR

• Kathleen Schwarz, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 6, 2011
• First Posted: June 8, 2011
• Study Start: September 1, 2012
• Primary Completion: December 23, 2016
• Study Completion: December 23, 2016
• Last Updated: May 26, 2022
• Results First Posted: July 3, 2018

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: At completion of HBRN project. Length of availability determined by NIDDK data repository.
• Access Criteria: Per NIDDK-supported data repository.

Locations

CA (1); US (6)