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

NCT ID: NCT01368497

Last Updated: 2022-05-26

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-09-30

Study Completion Date

2016-12-23

Brief Summary

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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.

Detailed Description

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This single arm treatment study was conducted by the pediatric centers within the National Institute of Diabetes Digestive and Kidney Diseases (NIDDK)-sponsored Hepatitis B Research Network (HBRN). Children age 3-\<18 years with immunotolerant chronic hepatitis B (CHB) infection who fulfilled the entry criteria received entecavir as monotherapy for 8 weeks and then combination therapy with entecavir and pegylated interferon by weekly subcutaneous injection until week 48. Children were to be followed for 48 weeks after discontinuation of therapy (week 96 for those who completed 48 weeks of treatment).

Assessment was undertaken at baseline, weeks 4, 8, 10, 12, 14, \& 16, then every 4 weeks until week 48, and then 4, 8, 12, 24,36, and 48 weeks following treatment discontinuation corresponding to weeks 52, 56, 60, 72, 84 and 96 for those who received treatment for 48 weeks. Blood work was drawn to measure markers of viral and liver disease status and for research biospecimen banking.

Participants were to receive therapy until week 48 and enter 48 weeks of follow-up thereafter. Participants who experienced a sustained elevation of alanine aminotransferase (ALT) were eligible to receive treatment as recommended by their hepatologist and continued to complete the study protocol.

Conditions

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Hepatitis B

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Entecavir and peginterferon

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

Group Type EXPERIMENTAL

Entecavir and peginterferon

Intervention Type 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).

Interventions

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Entecavir and peginterferon

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).

Intervention Type DRUG

Other Intervention Names

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PEGASYS, peginterferon alfa 2a, Baraclude

Eligibility Criteria

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Inclusion Criteria

* Enrolled in \& completed the baseline evaluation in NCT01263600 OR completed necessary components of NCT01263600 baseline evaluation by the end of the baseline visit.
* 3 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.

Exclusion Criteria

* 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.
* History or other evidence of chronic pulmonary disease associated with functional limitation.
* History of significant cardiovascular diseases.
* History of a severe seizure disorder or current anticonvulsant use.
* History or other evidence of severe retinopathy.
* History of thyroid disease poorly controlled on prescribed medications. Participants with elevated thyroid stimulating hormone concentrations with elevation of antibodies to thyroid peroxidase and any clinical manifestations of thyroid disease are excluded.
* Concomitant use or use during ≤ 6 months prior to the first dose of study drug of anti-neoplastic, immunosuppressive, nephrotoxic or hepatotoxic medication, methadone, theophylline or medications that may affect renal excretion or hepatic metabolism are not permitted.
* Concomitant use of complementary or alternative medications purported to have antiviral activity.
* A participant may not be co-enrolled in another clinical trial where an investigational drug is administered.
* Any other condition or situation that in the opinion of a study physician would make the participant unsuitable for enrollment or could interfere with the participant participating in and completing the study.
Minimum Eligible Age

3 Years

Maximum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Averell Sherker, MD

Role: STUDY_CHAIR

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

Ed Doo, MD

Role: STUDY_CHAIR

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

Kathleen Schwarz, MD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Locations

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University of California San Francisco Medical Center

San Francisco, California, United States

Site Status

Johns Hopkins University

Baltimore, Maryland, United States

Site Status

University of Minnesota

Minneapolis, Minnesota, United States

Site Status

Saint Louis Children's Medical Center

St Louis, Missouri, United States

Site Status

University of Texas Southwestern

Dallas, Texas, United States

Site Status

Seattle Children's Hospital

Seattle, Washington, United States

Site Status

Hospital of Sick Children

Toronto, Ontario, Canada

Site Status

Countries

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United States Canada

References

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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.

Reference Type BACKGROUND
PMID: 24318082 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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U01DK082916

Identifier Type: NIH

Identifier Source: secondary_id

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U01DK082864

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01DK082874

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01DK082944

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01DK082843

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01DK082871

Identifier Type: NIH

Identifier Source: secondary_id

View Link

UL1TR000423

Identifier Type: NIH

Identifier Source: secondary_id

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UL1TR000004

Identifier Type: NIH

Identifier Source: secondary_id

View Link

A-DK-3002-001

Identifier Type: OTHER

Identifier Source: secondary_id

DK082864 HBRN IT Peds Trial

Identifier Type: -

Identifier Source: org_study_id

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