Clinical trial NCT02263079: 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
Official title: A Phase IIIb, Randomized, Open-Label Study of Pegylated Interferon Alfa-2A in Combination With Lamivudine or Entecavir Compared With Untreated Control Patients in Children With HBeAg Positive Chronic Hepatitis B in the Immune-Tolerant Phase
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pediatric Immuno-Tolerant Chronic Hepatitis B
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2014-10-13
Enrollment: 62
Sex: ALL
Minimum age (years): 3
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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)

Primary outcomes:
measure: Percentage of Participants With Loss of Hepatitis B Surface Antigen (HBsAg) at 24 Weeks Post-End of Treatment/End of Untreated Observation
timeFrame: 24 weeks post-treatment/at the end of untreated observation (Week 80)
Secondary outcomes:
measure: Percentage of Participants With Loss of HBsAg
timeFrame: 1 year post-end of treatment (End of treatment = Week 56)
measure: Percentage of Participants With Loss of Hepatitis B Virus Envelope Antigen (HBeAg)
timeFrame: 24 weeks post-treatment /end of untreated observation (Week 80), and 1 year post-end of treatment (End of treatment = Week 56)
measure: Percentage of Participants With Seroconversion to Hepatitis B Surface Antibody (Anti-HBs), Defined as Loss of HBsAg and Presence of Anti-HBs
timeFrame: 24 weeks post-treatment /end of untreated observation (Week 80), and 1 year post-end of treatment (End of treatment = Week 56)
measure: Percentage of Participants With Seroconversion to Hepatitis B Envelope Antibody (Anti-HBe), Defined as Loss of HBeAg and Presence of Anti-HBe
timeFrame: 24 weeks post-treatment /end of untreated observation (Week 80), and 1 year post-end of treatment (End of treatment = Week 56)
measure: 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)
timeFrame: 24 weeks post-treatment /end of untreated observation (Week 80), and 1 year post-end of treatment (End of treatment = Week 56)
measure: Change From Baseline in HBV DNA Levels in the Peg-INF-Alfa-2A (Treated) Arm
timeFrame: Baseline, Week 8, 20, 32, 44, 56, Follow up Week 4 and 24
measure: Change From Baseline in HBV DNA Levels in the Untreated Control Participants
timeFrame: Baseline, Week 32, 56 and end of untreated observation (Week 80)
measure: 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
timeFrame: 24 weeks post-treatment /end of untreated observation (Week 80), and 1 year post-end of treatment (End of treatment = Week 56)
measure: 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
timeFrame: 24 weeks post-treatment /end of untreated observation (Week 80), and 1 year post-end of treatment (End of treatment = Week 56)
measure: Percentage of Participants With Adverse Events (AEs)
timeFrame: Baseline up to 24 weeks post-treatment/end of untreated observation (Week 80)
measure: Percentage of Participants With AEs Leading to Dose Modification or Interruption
timeFrame: Baseline up to 24 weeks post-end of treatment
measure: Serum Concentration of Peg-INF-Alfa-2A
timeFrame: At Weeks 12, 16, 20, 32, 44, 56
Other outcomes:
Locations:
city: Kansas City
country: United States
facility: Children's Mercy Hosp Clinics
state: Missouri
city: New York
country: United States
facility: Columbia University
state: New York
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
city: North Adelaide
country: Australia
facility: Womens and Childrens Hospital; Department of Gastroenterology
state: South Australia
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires St-Luc
city: Gent
country: Belgium
facility: UZ Gent
city: Essen
country: Germany
facility: Universitätsklinikum Essen; Klinik für Kinder- und Jugendmedizin Pädiatrie II
city: Mainz
country: Germany
facility: Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Zentrum für Kinder- und Jugendmedizin
city: München
country: Germany
facility: Dr. von Haunerschen Kinderspital, Kinderchirurgische Klinik und Poliklinik
city: Wuppertal
country: Germany
facility: HELIOS Klinikum Wuppertal, Zentrum für Kinder- und Jugendmedizin, Universität Witten-Herdecke
city: Bologna
country: Italy
facility: Azienda Ospedaliero-Universitaria Policlinico S. Orsola Malpighi; U.O. Malattie Infettive
state: Emilia-Romagna
city: Kuala Lumpur
country: Malaysia
facility: University Malaya Medical Center; Department of Paediatrics
city: Bucharest
country: Romania
facility: Grigore Alexandrescu Emergency Clinical Hospital for Children
city: Saint Petersburg
country: Russian Federation
facility: FSI Scientific research Institute of children's infections
city: Samara
country: Russian Federation
facility: MC Gepatolog
city: Taoyuan County
country: Taiwan
facility: Chang-Gung Memorial Hospital-Linkou; Division of Pediatric Gastroenterology, Dept Pediatrics
city: Adana
country: Turkey
facility: Cukurova University Medical School Department of Pediatrics; Pediatric Infectious Diseases
city: Ankara
country: Turkey
facility: Ankara University School of Medicine, Pediatrics Department; Pediatric Gastroenterology
city: Ankara
country: Turkey
facility: Hacettepe Uni , School of Medicine; Gastroenterology
city: Ankara
country: Turkey
facility: Gazi Universitesi Tip Fakultesi Pediyatri Anabilim Dalı; Pediyatrik Gastroenteroloji
city: Kyiv
country: Ukraine
facility: SI Institute of the pediatrics, obstetrics and gynecology
city: Birmingham
country: United Kingdom
facility: Birmingham Children'S Hopsital; Liver Unit
city: Leeds
country: United Kingdom
facility: Leeds Teaching Hospitals NHS Trust
city: London
country: United Kingdom
facility: Kings College Hospital NHS Foundation Trust
city: Manchester
country: United Kingdom
facility: North Manchester General Hospital
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: