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

Roche

Status and phase: Completed; Phase 3

Conditions: Pediatric Immuno-Tolerant Chronic Hepatitis B

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT02263079

2006-000977-31 (EudraCT Number)

NV25361

Details and patient eligibility

About

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

Enrollment: 62 patients

Sex: All

Ages: 3 to 17 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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)

Exclusion criteria

• 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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

62 participants in 3 patient groups

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

Experimental group

Description:

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.

Treatment:

Drug: Pegylated Interferon Alfa-2A

Drug: Entecavir

Drug: Lamivudine

Untreated Control Participants

No Intervention group

Description:

Untreated control participants will be observed up to 80 weeks.

Peg-INF-Alfa-2A Monotherapy

Experimental group

Description:

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

Treatment:

Drug: Pegylated Interferon Alfa-2A