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Phase 3 N=62 Randomized Treatment

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

Pediatric Immuno-Tolerant Chronic Hepatitis B

Enrolled (actual)
62
Serious AEs
1.6%
Results posted
Aug 2020
Primary outcome: Primary: Percentage of Participants With Loss of Hepatitis B Surface Antigen (HBsAg) at 24 Weeks Post-End of Treatment/End of Untreated Observation — 3.8; 0 Percentage of Participants

Study Design & Population

Study type
Interventional
Phase
Phase 3
Interventions
Entecavir (Drug); Lamivudine (Drug); Pegylated Interferon Alfa-2A (Drug)
Age
Pediatric · 3+ yrs
Sex
All
Sponsor
Hoffmann-La Roche
Primary completion
Jan 2020

Outcome Measures

OutcomeResultp-value
PRIMARY
Percentage of Participants With Loss of Hepatitis B Surface Antigen (HBsAg) at 24 Weeks Post-End of Treatment/End of Untreated Observation
3.8; 0
SECONDARY
Percentage of Participants With Loss of HBsAg
3.8
SECONDARY
Percentage of Participants With Loss of Hepatitis B Virus Envelope Antigen (HBeAg)
3.8; 12.1; 11.5
SECONDARY
Percentage of Participants With Seroconversion to Hepatitis B Surface Antibody (Anti-HBs), Defined as Loss of HBsAg and Presence of Anti-HBs
3.8; 0.0; 3.8
SECONDARY
Percentage of Participants With Seroconversion to Hepatitis B Envelope Antibody (Anti-HBe), Defined as Loss of HBeAg and Presence of Anti-HBe
0.0; 9.1; 7.7
SECONDARY
Percentage of Participants With Different Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels (Less Than [<] 20,000 International Units Per Milliliter [IU/mL], < 2000 IU/mL, or Undetectable HBV DNA)
7.7; 12.1; 7.7; 12.1; 0.0; 6.1
SECONDARY
Change From Baseline in HBV DNA Levels in the Peg-INF-Alfa-2A (Treated) Arm
8.02; 4.74; 3.54; 2.56; 2.15; 2.21
SECONDARY
Change From Baseline in HBV DNA Levels in the Untreated Control Participants
8.22; 8.29; 7.57; 7.24
SECONDARY
Percentage of Participants With Combined Response for HBeAg Seroconversion (Defined as Loss of HBeAg and Presence of Anti-HBe) and HBV DNA Levels <20,000 IU/mL
0.0; 9.1; 7.7
SECONDARY
Percentage of Participants With Combined Response for HBeAg Seroconversion (Defined as Loss of HBeAg and Presence of Anti-HBe) and HBV DNA Levels <2000 IU/mL
0.0; 9.1; 7.7
SECONDARY
Percentage of Participants With Adverse Events (AEs)
92.3; 45.5; 0; 3.0
SECONDARY
Percentage of Participants With AEs Leading to Dose Modification or Interruption
23.0
SECONDARY
Serum Concentration of Peg-INF-Alfa-2A
8430; 16300; 13800; 14900; 22700; 23000

Summary

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

Eligibility Criteria

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)
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT02263079). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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