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

Hepatitis B, Chronic Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01519960
• Other study ID #: YV25718
• Secondary ID: 2011-002732-70
• Status: Completed
• Phase: Phase 3
• Start date: July 11, 2012
• Est. completion date: October 18, 2021

Study information

• Verified date: October 2022
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 165
• Est. completion date: October 18, 2021
• Est. primary completion date: July 9, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years to 17 Years

Eligibility

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

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic

Intervention

Drug:
• peginterferon alfa-2a [Pegasys]
Body surface area adapted doses of 45-180 mcg subcutaneously weekly for 48 weeks, Weeks 1- 48
• 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

Locations

Country	Name	City	State
Australia	Royal Children's Hospital; Department of Gastroenterology	Melbourne	Victoria
Australia	Womens and Childrens Hospital; Department of Gastroenterology	North Adelaide	South Australia
Belgium	Cliniques Universitaires St-Luc	Bruxelles
Belgium	UZ Gent	Gent
Bulgaria	Specialized Hospital for Active Treatment of Pediatrics Diseases; Clinic of Gastroenterology	Sofia
Bulgaria	University Hospital "St. Marine"; Dept. of Pediatrics	Varna
China	Beijing 302 Hospital; No. 2 Infectious Disease Section	Beijing
China	Beijing You An Hospital; Digestive Dept	Beijing City
China	the First Hospital of Jilin University	Changchun
China	Southwest Hospital , Third Military Medical University	Chongqing
China	The Eighth People's Hospital of Guangzhou	Guangzhou
China	The Third Affiliated Hospital of Sun Yat-Sen University	Guangzhou
China	The First Affilliated Hospital of Kunming Medical College	Kunming
China	Xinjiang Uygur Autonomous Region Hospital of Chinese Traditional Medicine	Urumqi (????)
China	Tongji Hosp, Tongji Med. Col, Huazhong Univ. of Sci. & Tech	Wuhan
China	First Affiliated Hospital of Medical College of Xi'an Jiaotong University	Xi'an
Germany	HELIOS Klinikum Wuppertal, Zentrum für Kinder- und Jugendmedizin, Universität Witten-Herdecke	Wuppertal
Israel	Rambam Medical Center	Haifa
Israel	Hadassah University Hospital - Ein Kerem	Jerusalem
Israel	Western Galilee Hospital - Nahariya	Nahariya
Italy	Uni Degli Studi Di Bologna - Policlinica S. Orsola; Inst. Di Malattie Infettive	Bologna	Emilia-Romagna
Poland	Wojewodzki Szpital Obserwacyjno-Zakazny; Oddzial Pediatrii, Chorób Infekcyjnych i Hepatologii	Bydgoszcz
Poland	Krakowski Szpital Specjalistyczny im Jana Pawla II; Oddzial Chorób Infekcyjnych Dzieci	Krakow
Poland	Wojewodzki Specjalistyczny Szpital im. Dr W.Bieganskiego; Oddzial Obserwacyjno-Zakazny dla Dzieci	Lodz
Russian Federation	SFI Sceintific Research institute of nutrition of RAMS	Moscow
Russian Federation	SI Sceintific children health center RAMS	Moscow
Russian Federation	FSI Scientific research Institute of children's infections	Saint Petersburg
Russian Federation	MC Gepatolog	Samara
Ukraine	Kyiv Children's Clinical Infectious Diseases Hospital	Kyiv
Ukraine	SI Institute of the pediatrics, obstetrics and gynecology	Kyiv
United Kingdom	Birmingham Children'S Hopsital; Liver Unit	Birmingham
United Kingdom	Imperial College Healthcare Trust	London
United Kingdom	Kings College Hospital NHS Foundation Trust	London
United States	Johns Hopkins Hospital - Pediatric Gastroenterology	Baltimore	Maryland
United States	Children's Hospital Boston-Harvard Medical School; Division of Gastoenterology	Boston	Massachusetts
United States	Texas Children's Hospital	Houston	Texas
United States	St. Louis University - Cardinal Glennon Children's Medical Center	Saint Louis	Missouri
United States	Univ of California SF, Benioff Children's Hospital; Pediatrics, Gastro, Hepatology & Nutrition	San Francisco	California
United States	Seattle Children's Hospital	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Bulgaria,  China,  Germany,  Israel,  Italy,  Poland,  Russian Federation,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)