A Phase IIIb study to openly compare a group treated with only pegylated interferon alfa-2a (PEG-IFN) to an untreated group in children with chronic hepatitis B (CHB) who are HBeAg positive (a marker of their stage of CHB infection).

Phase 1

Conditions: Treatment of HBeAg positive chronic hepatitis B (CHB) in children.
MedDRA version: 14.1Level: LLTClassification code 10008910Term: Chronic hepatitis BSystem Organ Class: 10021881 - Infections and infestations
Therapeutic area: Diseases [C] - Virus Diseases [C02]

Registration Number: EUCTR2011-002732-70-IT

Lead Sponsor: F. HOFFMANN - LA ROCHE LTD.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 161

Inclusion Criteria

• Male or female subjects aged 3 to <18 years old at baseline.
• Positive HBsAg for more than 6 months.
• Positive HBeAg and detectable HBV DNA at screening (subjects must have
>10,000 copies/mL [>2,000 IU/mL] as measured by PCR).
• Negative anti-HBs and anti-HBe at screening.
• A liver biopsy obtained within the past 2 years prior to baseline (and more than 6 months after the end of any previous therapy for Hepatitis B) to confirm the presence of advanced fibrosis or exclude cirrhosis
• Compensated liver disease (Child-Pugh Class A clinical classification)
• Elevated serum ALT >ULN but = 10 × ULN as determined by two abnormal values taken =14 days apart during the six months before the first dose of study drug with at least one of the determinations obtained =35 days prior to the first dose. Reference range at local site should be used.
• Normal thyroid gland function at screening assessed by TSH, FT3, FT4, TPO antibodies and TBG determination.
• Signed informed consent from legal guardian and willingness of legal guardian to abide by the requirements of the study, and signed assent from child if appropriate.
Are the trial subjects under 18? yes
Number of subjects for this age range: 160
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

•Subjects with cirrhosis
•Subjects who have received investigational drugs or licensed treatments with anti-HBV activity within 6 months prior to baseline (e.g. IFNs, systemic corticosteroids,
lamivudine, tenofovir, emtricitabine, adefovir, entecavir, telbivudine, systemic acyclovir, systemic famciclovir). (Exception: subjects 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.)
• Known hypersensitivity to PEG-IFN.
• Positive test results at screening for HAV IgM Ab, anti-HCV Ab, anti-HDV Ab or anti-HIV Ab.
• History or other evidence of a medical condition associated with chronic liver disease other than CHB.
• History or other evidence of bleeding from esophageal varices.
Decompensated liver disease (e.g. ascites, varices, Child-Pugh Class B or C clinical
classification).
• History or other evidence of metabolic liver disease.
• Suspicion of hepatocellular carcinoma on ultrasound or other liver imaging. (All subjects to have ultrasound during screening.)
• Screening Alfa-fetoprotein (AFP) =100 ng/mL.
• Screening neutrophil count <1.5 x 109 cells/L, platelet count <90 x 109 cells/L, or hemoglobin <11 g/dL for females and <12 g/dL for males.
• Screening serum creatinine concentration >1.5 x ULN for age or severe renal disease e.g. glomerulonephritis.
• Autoimmune hepatitis.
• History of immunologically mediated disease to include but not limited to:
inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus
erythematosus, autoimmune hemolytic anemia, scleroderma, severe psoriasis, or clinical evidence of rheumatoid arthritis.
• Major depression or history of psychiatric disorder, such as major psychoses, suicidal ideation, and/or suicide attempt, where clinical trial participation would be
inappropriate.
• History or other evidence of chronic pulmonary or cardiac disease associated with clinically significant functional limitation.
• History of thyroid disease poorly controlled on prescribed medications.
• Poorly controlled diabetes.
• History of solid organ or bone marrow transplantation.
• Evidence of an active or suspected cancer or a history of malignancy in which the risk of recurrence was/is >20% within 2 years.
• History of having received any systemic anti-neoplastic (including radiation) or immunomodulatory treatment (including systemic corticosteroids) =6 months prior to
the study baseline visit or the expectation that such treatment will be needed at any time during the study. (Exception: Topical corticosteroids, corticosteroids
prescribed as physiological replacement therapies, or short courses [= 7 days] of
systemic corticosteroids.)
• Coagulopathy (international normalized ratio >1.5), hemoglobinopathy, hemophilia,
or history of severe illness or other blood disorders that would make subject
unsuitable for the study.
• History of seizure disorder requiring treatment with anticonvulsant medication
(excluding febrile seizures).
• History or other evidence of severe retinopathy.
• History or other evidence of severe illness or any other conditions which would make the subject, in the opinion of the investigator, unsuitable for the study.
• Active substance abuse within the last 6 months before the study.
• Sexually active females of childbearing potential and sexually active males who are not willing to utilize reliable contraception during the treatment/principal observation
period and

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Primary end point(s): HBeAg seroconversion (loss of HBeAg and presence of anti-HBe).;Timepoint(s) of evaluation of this end point: At the 24 week <br>post-treatment/principal observation period follow-up visit.;Main Objective: To compare HBeAg seroconversion (loss of HBeAg and presence of anti-<br>HBe) between a group treated with PEG-IFN monotherapy and an<br>untreated control group.;Secondary Objective: To examine the short and longer term effects on various efficacy and safety measures between a group treated with PEG-IFN monotherapy and an untreated control group, and to evaluate pharmacokinetics (PK) in PEG-IFN treated subjects.

Secondary Outcome Measures

Name	Time	Method

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