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



Status:Completed
Conditions:Hepatitis
Therapuetic Areas:Immunology / Infectious Diseases
Healthy:No
Age Range:3 - 18
Updated:9/23/2018
Start Date:September 2012
End Date:December 23, 2016

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Clinical Trial of Entecavir/Pegylated Interferon in Immune Tolerant Children With Chronic HBV Infection (HBRN)

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.

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.

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.
We found this trial at
7
sites
3400 N Charles St
Baltimore, Maryland 21205
410-516-8000
Johns Hopkins University The Johns Hopkins University opened in 1876, with the inauguration of its...
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Minneapolis, Minnesota 55455
(612) 625-5000
Univ of Minnesota With a flagship campus in the heart of the Twin Cities, and...
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Dallas, Texas 75390
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Saint Louis, Missouri 63104
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Saint Louis, MO
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505 Parnassus Ave
San Francisco, California 94143
(415) 476-1000
University of California, San Francisco Medical Center UCSF Medical Center is recognized throughout the world...
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San Francisco, CA
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4800 Sand Point Way NE
Seattle, Washington 98105
(206) 987-2000
Seattle Children's Hospital Seattle Children’s Hospital specializes in meeting the unique physical, emotional and developmental...
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Seattle, WA
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555 University Avenue
Toronto, Ontario M5G 1X8
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Toronto,
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