A Study of Pegasys (Peginterferon Alfa-2a) Versus Untreated Control in Children With HBeAg Positive Chronic Hepatitis B

A Phase IIIb Parallel Group, Open Label Study of Pegylated Interferon Alfa-2a Monotherapy (PEG-IFN, Ro 25-8310) Compared to Untreated Control in Children With HBeAg Positive Chronic Hepatitis B

This parallel group, open label study will evaluate the safety and efficacy of Pegasys (peginterferon alfa-2a) versus untreated control in children (age 3 years to <18 years at baseline) with HBeAg positive chronic hepatitis B. Children without advanced fibrosis and without cirrhosis will be randomized 2:1 to treatment Group A, receiving Pegasys 45-180 mcg subcutaneously weekly for 48 weeks, or to the untreated control Group B. Children with advanced fibrosis will be assigned to treatment group C and receive 48 weeks of treatment with Pegasys. Children in the untreated control Group B who have not experienced seroconversion 48 weeks after randomization may enter the Switch Arm to receive 48 weeks of Pegasys treatment. This offer will be available for 1 year following 48 weeks from randomization. Anticipated time on study treatment is 48 weeks. All subjects will be followed up for 5 years after the end of treatment (A,C,Switch)/principal observation (B) period.

Study Overview

• Status: Completed
• Conditions: Hepatitis B, Chronic
• Intervention / Treatment: Drug: peginterferon alfa-2a [Pegasys]; Drug: peginterferon alfa-2a [Pegasys]

• Study Type: Interventional
• Enrollment (Actual): 165
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • South Australia
    • North Adelaide, South Australia, Australia, 5006
      • Womens and Childrens Hospital; Department of Gastroenterology
  • Victoria
    • Melbourne, Victoria, Australia, 3053
      • Royal Children's Hospital; Department of Gastroenterology
• Belgium
  • Bruxelles, Belgium, 1200
    • Cliniques Universitaires St-Luc
  • Gent, Belgium, 9000
    • UZ Gent
• Bulgaria
  • Sofia, Bulgaria, 1612
    • Specialized Hospital for Active Treatment of Pediatrics Diseases; Clinic of Gastroenterology
  • Varna, Bulgaria, 9000
    • University Hospital "St. Marine"; Dept. of Pediatrics
• China
  • Beijing, China, 100039
    • Beijing 302 Hospital; No. 2 Infectious Disease Section
  • Beijing City, China, 100069
    • Beijing You An Hospital; Digestive Dept
  • Changchun, China, 130021
    • The First Hospital of Jilin University
  • Chongqing, China, 400038
    • Southwest Hospital , Third Military Medical University
  • Guangzhou, China, 510060
    • The Eighth People's Hospital of Guangzhou
  • Guangzhou, China, 510630
    • The Third Affiliated Hospital of Sun Yat-Sen University
  • Kunming, China, 650032
    • The First Affilliated Hospital of Kunming Medical College
  • Urumqi (乌鲁木齐), China, 830000
    • Xinjiang Uygur Autonomous Region Hospital of Chinese Traditional Medicine
  • Wuhan, China, 430030
    • Tongji Hosp, Tongji Med. Col, Huazhong Univ. of Sci. & Tech
  • Xi'an, China, 710061
    • First Affiliated Hospital of Medical College of Xi'an Jiaotong University
• Germany
  • Wuppertal, Germany, 42283
    • HELIOS Klinikum Wuppertal, Zentrum für Kinder- und Jugendmedizin, Universität Witten-Herdecke
• Israel
  • Haifa, Israel, 3109601
    • Rambam Medical Center
  • Jerusalem, Israel, 9112001
    • Hadassah University Hospital - Ein Kerem
  • Nahariya, Israel, 22100
    • Western Galilee Hospital - Nahariya
• Italy
  • Emilia-Romagna
    • Bologna, Emilia-Romagna, Italy, 40138
      • Uni Degli Studi Di Bologna - Policlinica S. Orsola; Inst. Di Malattie Infettive
• Poland
  • Bydgoszcz, Poland, 85-030
    • Wojewodzki Szpital Obserwacyjno-Zakazny; Oddział Pediatrii, Chorób Infekcyjnych i Hepatologii
  • Krakow, Poland, 31-202
    • Krakowski Szpital Specjalistyczny im Jana Pawła II; Oddział Chorób Infekcyjnych Dzieci
  • Łodz, Poland, 91-347
    • Wojewodzki Specjalistyczny Szpital im. Dr W.Bieganskiego; Oddział Obserwacyjno-Zakażny dla Dzieci
• Russian Federation
  • Moscow, Russian Federation, 119991
    • SI Sceintific children health center RAMS
  • Moscow, Russian Federation, 115446
    • SFI Sceintific Research institute of nutrition of RAMS
  • Saint Petersburg, Russian Federation, 197022
    • FSI Scientific research Institute of children's infections
  • Samara, Russian Federation, 443100
    • MC Gepatolog
• Ukraine
  • Kyiv, Ukraine, 04050
    • SI Institute of the pediatrics, obstetrics and gynecology
  • Kyiv, Ukraine, 01119
    • Kyiv Children's Clinical Infectious Diseases Hospital
• United Kingdom
  • Birmingham, United Kingdom, B4 6NH
    • Birmingham Children'S Hopsital; Liver Unit
  • London, United Kingdom, SE5 9RS
    • Kings College Hospital NHS Foundation Trust
  • London, United Kingdom, W2 1PG
    • Imperial College Healthcare Trust
• United States
  • California
    • San Francisco, California, United States, 94143
      • Univ of California SF, Benioff Children's Hospital; Pediatrics, Gastro, Hepatology & Nutrition
  • Maryland
    • Baltimore, Maryland, United States, 21287-5554
      • Johns Hopkins Hospital - Pediatric Gastroenterology
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Children's Hospital Boston-Harvard Medical School; Division of Gastoenterology
  • Missouri
    • Saint Louis, Missouri, United States, 63104
      • St. Louis University - Cardinal Glennon Children's Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female patients, 3 years to <18 years of age at baseline
• Positive HBsAg for more than 6 months
• Positive HBeAg and detectable HBV DNA at screening
• A liver biopsy obtained within the past 2 years prior to baseline (and more than 6 months after the end of previous therapy for hepatitis B) to confirm the presence of advanced fibrosis or exclude cirrhosis
• Compensated liver disease (Child-Pugh Class A)
• Elevated serum alanine transferase (ALT)
• Normal thyroid gland function at screening

Exclusion Criteria:

• Subjects with cirrhosis
• Subjects must not have received investigational drugs or licensed treatments with anti-HBV activity within 6 months of baseline. Subjects who are expected to need systemic antiviral therapy other than that provided by the study at any time during their participation in the study are also excluded
• Known hypersensitivity to peginterferon
• Positive test results at screening for hepatitis A, hepatitis C, hepatitis D or HIV infection
• History or evidence of medical condition associated with chronic liver disease other than chronic hepatitis B
• History or evidence of bleeding from esophageal varices
• Decompensated liver disease (e.g. ascites, Child-Pugh Class B or C)
• History of immunologically mediated disease
• Pregnant or lactating females

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A Pegasys	Drug: peginterferon alfa-2a [Pegasys]; Body surface area adapted doses of 45-180 mcg subcutaneously weekly for 48 weeks, Weeks 1- 48; Drug: peginterferon alfa-2a [Pegasys]; Body surface area adapted doses of 45-180 mcg subcutaneously weekly for 48 weeks, after Week 48 for Group B patients who have not experienced HBeAg seroconversion
No Intervention: B Untreated Control
Experimental: C Fibrosis non-randomized	Drug: peginterferon alfa-2a [Pegasys]; Body surface area adapted doses of 45-180 mcg subcutaneously weekly for 48 weeks, Weeks 1- 48; Drug: peginterferon alfa-2a [Pegasys]; Body surface area adapted doses of 45-180 mcg subcutaneously weekly for 48 weeks, after Week 48 for Group B patients who have not experienced HBeAg seroconversion
Experimental: Switch	Drug: peginterferon alfa-2a [Pegasys]; Body surface area adapted doses of 45-180 mcg subcutaneously weekly for 48 weeks, Weeks 1- 48; Drug: peginterferon alfa-2a [Pegasys]; Body surface area adapted doses of 45-180 mcg subcutaneously weekly for 48 weeks, after Week 48 for Group B patients who have not experienced HBeAg seroconversion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With HBeAg Seroconversion at 24 Weeks After End of Treatment (EOT)/POP in Groups A and B	HBeAg seroconversion was defined as loss of HBeAg and the presence of hepatitis B envelope antibody (anti-HBe). The percentage of participants with HBeAg seroconversion at 24 weeks after EOT/POP was reported. The 95 percent (%) confidence interval (CI) was calculated by the Pearson-Clopper method. Intent-to-Treat (ITT) Population: All randomized participants regardless of treatment received.	FU Week 24 (up to 72 weeks overall)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Loss of HBeAg at 24 Weeks After EOT/POP in Groups A and B	The percentage of participants with loss of HBeAg at 24 weeks after EOT/POP was reported. The 95% CI was calculated by the Pearson-Clopper method. ITT Population.	FU Week 24 (up to 72 weeks overall)
Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Seroconversion at 24 Weeks After EOT/POP in Groups A and B	HBsAg seroconversion was defined as loss of HBsAg and the presence of hepatitis B surface antibody (anti-HBs). The percentage of participants with HBsAg seroconversion at 24 weeks after EOT/POP was reported. The 95% CI was calculated by the Pearson-Clopper method. ITT Population.	FU Week 24 (up to 72 weeks overall)
Percentage of Participants With Normal ALT at 24 Weeks After EOT/POP in Groups A and B	Normal ALT was defined as ALT less than or equal to (≤) ULN, where each ULN was given by the laboratory at which the sample was analyzed. The percentage of participants with normal ALT at 24 weeks after EOT/POP was reported. The 95% CI was calculated by the Pearson-Clopper method. ITT Population.	FU Week 24 (up to 72 weeks overall)
Percentage of Participants With HBV Deoxyribonucleic Acid (DNA) <20,000 International Units Per Milliliter (IU/mL) at 24 Weeks After EOT/POP in Groups A and B	HBV DNA was quantified using polymerase chain reaction (PCR) by Roche Taqman. The percentage of participants with HBV DNA <20,000 IU/mL at 24 weeks after EOT/POP was reported. The 95% CI was calculated by the Pearson-Clopper method. ITT Population.	FU Week 24 (up to 72 weeks overall)
Percentage of Participants With HBV DNA <2,000 IU/mL at 24 Weeks After EOT/POP in Groups A and B	HBV DNA was quantified using PCR by Roche Taqman. The percentage of participants with HBV DNA <2,000 IU/mL at 24 weeks after EOT/POP was reported. The 95% CI was calculated by the Pearson-Clopper method. ITT Population.	FU Week 24 (up to 72 weeks overall)
Percentage of Participants With Combined HBeAg Seroconversion and HBV DNA <20,000 IU/mL at 24 Weeks After EOT/POP in Groups A and B	HBeAg seroconversion was defined as loss of HBeAg and the presence of anti-HBe. HBV DNA was quantified using PCR by Roche Taqman. The percentage of participants with combined HBeAg seroconversion and HBV DNA <20,000 IU/mL at 24 weeks after EOT/POP was reported. The 95% CI was calculated by the Pearson-Clopper method. ITT Population.	FU Week 24 (up to 72 weeks overall)
Percentage of Participants With Combined HBeAg Seroconversion and HBV DNA <2,000 IU/mL at 24 Weeks After EOT/POP in Groups A and B	HBeAg seroconversion was defined as loss of HBeAg and the presence of anti-HBe. HBV DNA was quantified using PCR by Roche Taqman. The percentage of participants with combined HBeAg seroconversion and HBV DNA <2,000 IU/mL at 24 weeks after EOT/POP was reported. The 95% CI was calculated by the Pearson-Clopper method. ITT Population.	FU Week 24 (up to 72 weeks overall)
Percentage of Participants With HBeAg Seroconversion at EOT/POP in Groups A and B	HBeAg seroconversion was defined as loss of HBeAg and the presence of anti-HBe. The percentage of participants with HBeAg seroconversion at EOT/POP was reported. The 95% CI was calculated by the Pearson-Clopper method. ITT Population.	Week 48
Percentage of Participants With Loss of HBeAg at EOT/POP in Groups A and B	The percentage of participants with loss of HBeAg at EOT/POP was reported. The 95% CI was calculated by the Pearson-Clopper method. ITT Population.	Week 48
Percentage of Participants With HBsAg Seroconversion at EOT/POP in Groups A and B	HBsAg seroconversion was defined as loss of HBsAg and the presence of anti-HBs. The percentage of participants with HBsAg seroconversion at EOT/POP was reported. The 95% CI was calculated by the Pearson-Clopper method. ITT Population.	Week 48
Percentage of Participants With Loss of HBsAg at EOT/POP in Groups A and B	The percentage of participants with loss of HBsAg at EOT/POP was reported. The 95% CI was calculated by the Pearson-Clopper method. ITT Population.	Week 48
Percentage of Participants With Normal ALT at EOT/POP in Groups A and B	Normal ALT was defined as ALT ≤ ULN, where each ULN was given by the laboratory at which the sample was analyzed. The percentage of participants with normal ALT at EOT/POP was reported. The 95% CI was calculated by the Pearson-Clopper method. ITT Population.	Week 48
Percentage of Participants With HBV DNA <20,000 IU/mL at EOT/POP in Groups A and B	HBV DNA was quantified using PCR by Roche Taqman. The percentage of participants with HBV DNA <20,000 IU/mL at EOT/POP was reported. The 95% CI was calculated by the Pearson-Clopper method. ITT Population.	Week 48
Percentage of Participants With HBV DNA <2,000 IU/mL at EOT/POP in Groups A and B	HBV DNA was quantified using PCR by Roche Taqman. The percentage of participants with HBV DNA <2,000 IU/mL at EOT/POP was reported. The 95% CI was calculated by the Pearson-Clopper method. ITT Population.	Week 48
Percentage of Participants With HBV DNA Undetectable at EOT/POP in Groups A and B	HBV DNA was quantified using PCR by Roche Taqman. Undetectable HBV DNA was defined as HBV DNA <29 IU/mL. The percentage of participants with HBV DNA undetectable at EOT/POP was reported. The 95% CI was calculated by the Pearson-Clopper method. ITT Population.	Week 48
Percentage of Participants With Combined HBeAg Seroconversion and HBV DNA <20,000 IU/mL at EOT/POP in Groups A and B	HBeAg seroconversion was defined as loss of HBeAg and the presence of anti-HBe. HBV DNA was quantified using PCR by Roche Taqman. The percentage of participants with combined HBeAg seroconversion and HBV DNA <20,000 IU/mL at EOT/POP was reported. The 95% CI was calculated by the Pearson-Clopper method. ITT Population.	Week 48
Percentage of Participants With Combined HBeAg Seroconversion and HBV DNA <2,000 IU/mL at EOT/POP in Groups A and B	HBeAg seroconversion was defined as loss of HBeAg and the presence of anti-HBe. HBV DNA was quantified using PCR by Roche Taqman. The percentage of participants with combined HBeAg seroconversion and HBV DNA <2,000 IU/mL at EOT/POP was reported. The 95% CI was calculated by the Pearson-Clopper method. ITT Population.	Week 48
Quantitative Serum ALT Level in Groups A and B	Quantitative ALT at each visit was averaged among all participants and expressed as a factor of the laboratory-specific ULN (for example, 1 × ULN, 2 × ULN, 3 × ULN). ITT Population. The number of participants who provided evaluable data for the analysis at each timepoint (n) is shown in the table.	Baseline; Weeks 1, 2, 4, 8, 12, 18, 24, 30, 36, 42, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall)
Quantitative HBV DNA Level in Groups A and B	Quantitative HBV DNA at each visit was averaged among all participants and expressed in log10 IU/mL. ITT Population. The number of participants who provided evaluable data for the analysis at each timepoint (n) is shown in the table.	Baseline; Weeks 12, 24, 36, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall)
Change From Baseline in Quantitative HBV DNA Level in Groups A and B	The change in quantitative HBV DNA from Baseline to each visit was averaged among all participants and expressed in log10 IU/mL. ITT Population. All participants were included in the endpoint analysis. The number of participants who provided evaluable data for the analysis at each timepoint (n) is shown in the table.	Weeks 12, 24, 36, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall)
Percentage of Participants With Loss of HBeAg at 24 Weeks After EOT in Group C	The percentage of participants with loss of HBeAg at 24 weeks after EOT was reported. The 95% CI was calculated by the Pearson-Clopper method. Safety Population: All participants who received at least one dose of study drug (if assigned) and had at least one post-baseline safety assessment.	FU Week 24 (up to 72 weeks overall)
Percentage of Participants With HBsAg Seroconversion at 24 Weeks After EOT in Group C	HBsAg seroconversion was defined as loss of HBsAg and the presence of anti-HBs. The percentage of participants with HBsAg seroconversion at 24 weeks after EOT was reported. The 95% CI was calculated by the Pearson-Clopper method. Safety Population.	FU Week 24 (up to 72 weeks overall)
Percentage of Participants With Loss of HBsAg at 24 Weeks After EOT in Group C	The percentage of participants with loss of HBsAg at 24 weeks after EOT was reported. The 95% CI was calculated by the Pearson-Clopper method. Safety Population	FU Week 24 (up to 72 weeks overall)
Percentage of Participants With Normal ALT at 24 Weeks After EOT in Group C	Normal ALT was defined as ALT ≤ ULN, where each ULN was given by the laboratory at which the sample was analyzed. The percentage of participants with normal ALT at 24 weeks after EOT was reported. The 95% CI was calculated by the Pearson-Clopper method. Safety Population.	FU Week 24 (up to 72 weeks overall)
Percentage of Participants With HBV DNA <20,000 IU/mL at 24 Weeks After EOT in Group C	HBV DNA was quantified using PCR by Roche Taqman. The percentage of participants with HBV DNA <20,000 IU/mL at 24 weeks after EOT was reported. The 95% CI was calculated by the Pearson-Clopper method. Safety Population.	FU Week 24 (up to 72 weeks overall)
Percentage of Participants With HBV DNA <2,000 IU/mL at 24 Weeks After EOT in Group C	HBV DNA was quantified using PCR by Roche Taqman. The percentage of participants with HBV DNA <2,000 IU/mL at 24 weeks after EOT was reported. The 95% CI was calculated by the Pearson-Clopper method. Safety Population.	FU Week 24 (up to 72 weeks overall)
Percentage of Participants With HBV DNA Undetectable at 24 Weeks After EOT in Group C	HBV DNA was quantified using PCR by Roche Taqman. Undetectable HBV DNA was defined as HBV DNA <29 IU/mL. The percentage of participants with HBV DNA undetectable at 24 weeks after EOT was reported. The 95% CI was calculated by the Pearson-Clopper method. Safety Population.	FU Week 24 (up to 72 weeks overall)
Percentage of Participants With Combined HBeAg Seroconversion and HBV DNA <20,000 IU/mL at 24 Weeks After EOT in Group C	HBeAg seroconversion was defined as loss of HBeAg and the presence of anti-HBe. HBV DNA was quantified using PCR by Roche Taqman. The percentage of participants with combined HBeAg seroconversion and HBV DNA <20,000 IU/mL at 24 weeks after EOT was reported. The 95% CI was calculated by the Pearson-Clopper method. Safety Population.	FU Week 24 (up to 72 weeks overall)
Percentage of Participants With Combined HBeAg Seroconversion and HBV DNA <2,000 IU/mL at 24 Weeks After EOT in Group C	HBeAg seroconversion was defined as loss of HBeAg and the presence of anti-HBe. HBV DNA was quantified using PCR by Roche Taqman. The percentage of participants with combined HBeAg seroconversion and HBV DNA <2,000 IU/mL at 24 weeks after EOT was reported. The 95% CI was calculated by the Pearson-Clopper method. Safety Population.	FU Week 24 (up to 72 weeks overall)
Percentage of Participants With HBeAg Seroconversion at EOT in Group C	HBeAg seroconversion was defined as loss of HBeAg and the presence of anti-HBe. The percentage of participants with HBeAg seroconversion at EOT was reported. The 95% CI was calculated by the Pearson-Clopper method. Safety Population.	Week 48
Percentage of Participants With Loss of HBeAg at EOT in Group C	The percentage of participants with loss of HBeAg at EOT was reported. The 95% CI was calculated by the Pearson-Clopper method. Safety Population.	Week 48
Percentage of Participants With HBsAg Seroconversion at EOT in Group C	HBsAg seroconversion was defined as loss of HBsAg and the presence of anti-HBs. The percentage of participants with HBsAg seroconversion at EOT was reported. The 95% CI was calculated by the Pearson-Clopper method. Safety Population.	Week 48
Percentage of Participants With Loss of HBsAg at EOT in Group C	The percentage of participants with loss of HBsAg at EOT was reported. The 95% CI was calculated by the Pearson-Clopper method. Safety Population.	Week 48
Percentage of Participants With Normal ALT at EOT in Group C	Normal ALT was defined as ALT ≤ ULN, where each ULN was given by the laboratory at which the sample was analyzed. The percentage of participants with normal ALT at EOT was reported. The 95% CI was calculated by the Pearson-Clopper method. Safety Population.	Week 48
Percentage of Participants With HBV DNA <20,000 IU/mL at EOT in Group C	HBV DNA was quantified using PCR by Roche Taqman. The percentage of participants with HBV DNA <20,000 IU/mL at EOT was reported. The 95% CI was calculated by the Pearson-Clopper method. Safety Population.	Week 48
Percentage of Participants With HBV DNA <2,000 IU/mL at EOT in Group C	HBV DNA was quantified using PCR by Roche Taqman. The percentage of participants with HBV DNA <2,000 IU/mL at EOT was reported. The 95% CI was calculated by the Pearson-Clopper method. Safety Population.	Week 48
Percentage of Participants With HBV DNA Undetectable at EOT in Group C	HBV DNA was quantified using PCR by Roche Taqman. Undetectable HBV DNA was defined as HBV DNA <29 IU/mL. The percentage of participants with HBV DNA undetectable at EOT was reported. The 95% CI was calculated by the Pearson-Clopper method. Safety Population.	Week 48
Percentage of Participants With Combined HBeAg Seroconversion and HBV DNA <20,000 IU/mL at EOT in Group C	HBeAg seroconversion was defined as loss of HBeAg and the presence of anti-HBe. HBV DNA was quantified using PCR by Roche Taqman. The percentage of participants with combined HBeAg seroconversion and HBV DNA <20,000 IU/mL at EOT was reported. The 95% CI was calculated by the Pearson-Clopper method. Safety Population.	Week 48
Percentage of Participants With Combined HBeAg Seroconversion and HBV DNA <2,000 IU/mL at EOT in Group C	HBeAg seroconversion was defined as loss of HBeAg and the presence of anti-HBe. HBV DNA was quantified using PCR by Roche Taqman. The percentage of participants with combined HBeAg seroconversion and HBV DNA <2,000 IU/mL at EOT was reported. The 95% CI was calculated by the Pearson-Clopper method. Safety Population.	Week 48
Quantitative Serum ALT Level in Group C	Quantitative ALT at each visit was averaged among all participants and expressed as a factor of the laboratory-specific ULN (for example, 1 × ULN, 2 × ULN, 3 × ULN). Safety Population. The number of participants who provided evaluable data for the analysis at each timepoint (n) is shown in the table.	Baseline; Weeks 1, 2, 4, 8, 12, 18, 24, 30, 36, 42, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall)
Quantitative HBV DNA Level in Group C	Quantitative HBV DNA at each visit was averaged among all participants and expressed in log10 IU/mL. Safety Population. The number of participants who provided evaluable data for the analysis at each timepoint (n) is shown in the table.	Baseline; Weeks 12, 24, 36, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall)
Change From Baseline in Quantitative HBV DNA Level in Group C	The change in quantitative HBV DNA from Baseline to each visit was averaged among all participants and expressed in log10 IU/mL. Safety Population. The number of participants who provided evaluable data for the analysis at each timepoint (n) is shown in the table.	Weeks 12, 24, 36, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall)
Estimated Area Under the Concentration-Time Curve (AUC) by BSA Category	AUC was estimated using population pharmacokinetic (PK) modeling. The AUC at steady-state was averaged among participants who received PEG-IFN and reported by BSA category. Categories of BSA-based dosing used in the analysis were as follows: 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg. The estimated AUC was expressed in hours by nanograms per milliliter (h*ng/mL). PK Substudy Population: All participants who consented to participate in the PK substudy. "Number of subjects analyzed" reflects the total combined number of participants who provided evaluable data across all BSA categories. The number of participants who provided evaluable data within each BSA category (n) is shown in the table.	Pre-dose (0 hours) at Baseline and Weeks 4, 8, 12, 24; post-dose (24-48, 72-96, 168 hours) during Weeks 1, 24 (up to 24 weeks overall)
Percentage of Participants With >15% Drop in Height Percentile for Age in Groups A and B	The percentage of participants with >15% drop in height percentile for age from Baseline to each visit was reported. Safety Population. "Number of subjects analyzed" reflects the total number of participants who provided evaluable data at any timepoint. The number of participants who provided evaluable data for the analysis at each timepoint (n) is shown in the table.	Weeks 12, 24, 36, 48; FU Weeks 12, 24 (up to 72 weeks overall)
Percentage of Participants With >15% Drop in Weight Percentile for Age in Groups A and B	The percentage of participants with >15% drop in weight percentile for age from Baseline to each visit was reported. Safety Population. "Number of subjects analyzed" reflects the total number of participants who provided evaluable data at any timepoint. The number of participants who provided evaluable data for the analysis at each timepoint (n) is shown in the table.	Weeks 4, 8, 12, 18, 24, 30, 36, 42, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall)
Quantitative HBeAg Level in Groups A and B	Quantitative HBeAg at each visit was averaged among all participants and expressed in log10 Paul Ehrlich Institute units per milliliter (PEIU/mL). ITT Population. All participants were included in the endpoint analysis. The number of participants who provided evaluable data for the analysis at each timepoint (n) is shown in the table.	Baseline; Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall)
Quantitative HBsAg Level in Groups A and B	Quantitative HBsAg at each visit was averaged among all participants and expressed in log10 IU/mL. ITT Population. All participants were included in the endpoint analysis. The number of participants who provided evaluable data for the analysis at each timepoint (n) is shown in the table.	Baseline; Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall)
Quantitative HBeAg Level in Group C	Quantitative HBeAg at each visit was averaged among all participants and expressed in log10 PEIU/mL. Safety Population. The number of participants who provided evaluable data for the analysis at each timepoint (n) is shown in the table.	Baseline; Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall)
Quantitative HBsAg Level in Group C	Quantitative HBsAg at each visit was averaged among all participants and expressed in log10 IU/mL. Safety Population.	Baseline; Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall)
Change From Baseline in Liver Stiffness Measure (LSM) in Groups A, B, C	Liver elastography was performed to assess elasticity and extent of hepatic fibrosis. The change in LSM from Baseline to each visit was averaged among all participants in expressed in kilopascals (kPa). Positive changes in LSM values corresponded to an increase in stiffness and hepatic fibrosis. Liver Substudy Population: All participants who consented to participate in the liver elasticity substudy. "Number of subjects analyzed" reflects the total number of participants who provided evaluable data at any timepoint. The number of participants who provided evaluable data for the analysis at each timepoint (n) is shown in the table.	Week 48; FU Week 24 (up to 72 weeks overall)
Percentage of Participants With >15% Drop in Height Percentile for Age in Group C	The percentage of participants with >15% drop in weight percentile for age from Baseline to each visit was reported. Safety Population.	Weeks 30, 36; FU Weeks 4, 12, 24 (up to 72 weeks overall)
Change From Baseline in Height for Age Z-Score in Groups A and B	The difference between the population mean and raw scores was calculated as the height for age z-score. Mean absolute values at Baseline were reported. The change from Baseline to each visit was averaged among all participants and expressed in units of standard deviations. Safety Population. "Number of subjects analyzed" reflects the total number of participants who provided evaluable data at any timepoint. The number of participants who provided evaluable data for the analysis at each timepoint (n) is shown in the table.	Baseline; Weeks 12, 24, 36, 48; FU Weeks 12, 24 (up to 72 weeks overall)
Change From Baseline in Weight for Age Z-Score in Groups A and B	The difference between the population mean and raw scores was calculated as the weight for age z-score. Mean absolute values at Baseline were reported. The change from Baseline to each visit was averaged among all participants and expressed in units of standard deviations.Safety Population. "Number of subjects analyzed" reflects the total number of participants who provided evaluable data at any timepoint. The number of participants who provided evaluable data for the analysis at each timepoint (n) is shown in the table.	Baseline; Weeks 1, 2, 4, 8, 12, 18, 24, 30, 36, 42, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall)
Change From Baseline in Height for Age Z-Score in Group C	The difference between the population mean and raw scores was calculated as the height for age z-score. Mean absolute values at Baseline were reported. The change from Baseline to each visit was averaged among all participants and expressed in units of standard deviations. Safety Population.	Baseline; Weeks 12, 24, 36, 48; FU Weeks 12, 24 (up to 72 weeks overall)
Change From Baseline in Weight for Age Z-Score in Group C	The difference between the population mean and raw scores was calculated as the weight for age z-score. Mean absolute values at Baseline were reported. The change from Baseline to each visit was averaged among all participants and expressed in units of standard deviations. Safety Population. The number of participants who provided evaluable data for the analysis at each timepoint (n) is shown in the table.	Baseline; Weeks 1, 2, 4, 8, 12, 18, 24, 30, 36, 42, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall)
Percentage of Participants With HBeAg Seroconversion at 24 Weeks After EOT in Group C	HBeAg seroconversion was defined as loss of HBeAg and the presence of anti-HBe. The percentage of participants with HBeAg seroconversion at 24 weeks after EOT was reported. The 95% CI was calculated by the Pearson-Clopper method. Safety Population.	FU Week 24 (up to 72 weeks overall)
Change From Baseline in Quantitative Serum ALT Level in Groups A and B	The change in quantitative ALT from Baseline to each visit was averaged among all participants and expressed as a factor of the laboratory-specific ULN (for example, 1 × ULN, 2 × ULN, 3 × ULN). ITT Population. All participants were included in the endpoint analysis. The number of participants who provided evaluable data for the analysis at each timepoint (n) is shown in the table.	Weeks 1, 2, 4, 8, 12, 18, 24, 30, 36, 42, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall)
Change From Baseline in Quantitative HBeAg Level in Groups A and B	The change in quantitative HBeAg from Baseline to each visit was averaged among all participants and expressed in log10 PEIU/mL. ITT Population. "Number of subjects analyzed" reflects the total number of participants who provided evaluable data at any timepoint. The number of participants who provided evaluable data for the analysis at each timepoint (n) is shown in the table.	Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall)
Change From Baseline in Quantitative HBsAg Level in Groups A and B	The change in quantitative HBsAg from Baseline to each visit was averaged among all participants and expressed in log10 IU/mL. ITT Population. "Number of subjects analyzed" reflects the total number of participants who provided evaluable data at any timepoint. The number of participants who provided evaluable data for the analysis at each timepoint (n) is shown in the table.	Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall)
Change From Baseline in Quantitative Serum ALT Level in Group C	The change in quantitative ALT from Baseline to each visit was averaged among all participants and expressed as a factor of the laboratory-specific ULN (for example, 1 × ULN, 2 × ULN, 3 × ULN). Safety Population. The number of participants who provided evaluable data for the analysis at each timepoint (n) is shown in the table.	Weeks 1, 2, 4, 8, 12, 18, 24, 30, 36, 42, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall)
Change From Baseline in Quantitative HBeAg Level in Group C	The change in quantitative HBeAg from Baseline to each visit was averaged among all participants and expressed in log10 PEIU/mL. Safety Population. "Number of subjects analyzed" reflects the total number of participants who provided evaluable data at any timepoint. The number of participants who provided evaluable data for the analysis at each timepoint (n) is shown in the table.	Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall)
Change From Baseline in Quantitative HBsAg Level in Group C	The change in quantitative HBsAg from Baseline to each visit was averaged among all participants and expressed in log10 IU/mL. Safety Population.	Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall)
Percentage of Participants With HBeAg Seroconversion Over Time in Groups A and B	HBeAg seroconversion was defined as loss of HBeAg and the presence of anti-HBe. The 95% CI was calculated by the Pearson-Clopper method. ITT Population.	Baseline, FU Years: 1, 2, 3, 4, 5
Percentage of Participants With Loss of HBeAg at 24 Weeks After the End of Switch Treatment Period: Switch Group	The percentage of participants with loss of HBeAg at 24 weeks after EOT/POP was reported. The 95% CI was calculated by the Pearson-Clopper method. ITT Population.	FU Week 24 (up to 72 weeks overall)
Percentage of Participants With HBsAg Seroconversion at 24 Weeks After the End of Switch Treatment Period: Switch Group	HBeAg seroconversion was defined as loss of HBeAg and the presence of hepatitis B envelope antibody (anti-HBe). The percentage of participants with HBeAg seroconversion at 24 weeks after EOT/POP was reported. The 95 percent (%) confidence interval (CI) was calculated by the Pearson-Clopper method. Intent-to-Treat (ITT) Population: All randomized participants regardless of treatment received.	FU Week 24 (up to 72 weeks overall)
Percentage of Participants With Loss of HBsAg at 24 Weeks After the End of Switch Treatment Period: Switch Group	HBeAg seroconversion was defined as loss of HBeAg and the presence of hepatitis B envelope antibody (anti-HBe). The percentage of participants with HBeAg seroconversion at 24 weeks after EOT/POP was reported. The 95 percent (%) confidence interval (CI) was calculated by the Pearson-Clopper method. Intent-to-Treat (ITT) Population: All randomized participants regardless of treatment received.	FU Week 24 (up to 72 weeks overall)
Percentage of Participants With Normal ALT at 24 Weeks After the End of Switch Treatment Period: Switch Group	Normal ALT was defined as ALT ≤ ULN, where each ULN was given by the laboratory at which the sample was analyzed. The percentage of participants with normal ALT at EOT/POP was reported. The 95% CI was calculated by the Pearson-Clopper method. ITT Population.	FU Week 24 (up to 72 weeks overall)
Percentage of Participants With HBV Deoxyribonucleic Acid (DNA) <20,000 International Units Per Milliliter (IU/mL) at 24 Weeks After the End of Switch Treatment Period: Switch Group	HBV DNA was quantified using polymerase chain reaction (PCR) by Roche Taqman. The percentage of participants with HBV DNA <20,000 IU/mL at 24 weeks after EOT/POP was reported. The 95% CI was calculated by the Pearson-Clopper method. ITT Population.	FU Week 24 (up to 72 weeks overall)
Percentage of Participants With HBV DNA <2,000 IU/mL at 24 Weeks After the End of Switch Treatment Period: Switch Group	HBV DNA was quantified using PCR by Roche Taqman. The percentage of participants with HBV DNA <2,000 IU/mL at 24 weeks after EOT/POP was reported. The 95% CI was calculated by the Pearson-Clopper method. ITT Population.	FU Week 24 (up to 72 weeks overall)
Percentage of Participants With HBV DNA Undetectable at 24 Weeks After the End of Switch Treatment Period: Switch Group	HBV DNA was quantified using PCR by Roche Taqman. Undetectable HBV DNA was defined as HBV DNA <29 IU/mL. The percentage of participants with HBV DNA undetectable at 24 weeks after EOT/POP was reported. The 95% CI was calculated by the Pearson-Clopper method. ITT Population.	FU Week 24 (up to 72 weeks overall)
Percentage of Participants With Combined HBeAg Seroconversion and HBV DNA <20,000 IU/mL at 24 Weeks After the End of Switch Treatment Period: Switch Group	HBeAg seroconversion was defined as loss of HBeAg and the presence of anti-HBe. HBV DNA was quantified using PCR by Roche Taqman. The 95% CI was calculated by the Pearson-Clopper method. ITT Population.	FU Week 24 (up to 72 weeks overall)
Percentage of Participants With Combined HBeAg Seroconversion and HBV DNA <2,000 IU/mL at 24 Weeks After the End of Switch Treatment Period: Switch Group	HBeAg seroconversion was defined as loss of HBeAg and the presence of anti-HBe. HBV DNA was quantified using PCR by Roche Taqman. The percentage of participants with combined HBeAg seroconversion and HBV DNA <2,000 IU/mL at 24 weeks after EOT/POP was reported. The 95% CI was calculated by the Pearson-Clopper method. ITT Population.	FU Week 24 (up to 72 weeks overall)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• Wirth S, Zhang H, Hardikar W, Schwarz KB, Sokal E, Yang W, Fan H, Morozov V, Mao Q, Deng H, Huang Y, Yang L, Frey N, Nasmyth-Miller C, Pavlovic V, Wat C. Efficacy and Safety of Peginterferon Alfa-2a (40KD) in Children With Chronic Hepatitis B: The PEG-B-ACTIVE Study. Hepatology. 2018 Nov;68(5):1681-1694. doi: 10.1002/hep.30050. Epub 2018 Oct 8.

Study record dates

Study Major Dates

• Study Start (Actual): July 11, 2012
• Primary Completion (Actual): July 9, 2015
• Study Completion (Actual): October 18, 2021

Study Registration Dates

• First Submitted: December 6, 2011
• First Submitted That Met QC Criteria: January 24, 2012
• First Posted (Estimate): January 27, 2012

Study Record Updates

• Last Update Posted (Actual): November 18, 2022
• Last Update Submitted That Met QC Criteria: October 26, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Hepatitis B; Hepatitis; Hepatitis A; Hepatitis B, Chronic; Physiological Effects of Drugs; Anti-Infective Agents; Antiviral Agents; Immunologic Factors; Interferon-alpha; Peginterferon alfa-2a
• Other Study ID Numbers: YV25718; 2011-002732-70 (EudraCT Number)