Clinical trial NCT01519960: A Study of Pegasys (Peginterferon Alfa-2a) Versus Untreated Control in Children With HBeAg Positive Chronic Hepatitis B
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hepatitis B, Chronic
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2012-01-27
Enrollment: 165
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 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.


Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants With HBeAg Seroconversion at 24 Weeks After End of Treatment (EOT)/POP in Groups A and B
timeFrame: FU Week 24 (up to 72 weeks overall)
Secondary outcomes:
measure: Percentage of Participants With Loss of HBeAg at 24 Weeks After EOT/POP in Groups A and B
timeFrame: FU Week 24 (up to 72 weeks overall)
measure: Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Seroconversion at 24 Weeks After EOT/POP in Groups A and B
timeFrame: FU Week 24 (up to 72 weeks overall)
measure: Percentage of Participants With Normal ALT at 24 Weeks After EOT/POP in Groups A and B
timeFrame: FU Week 24 (up to 72 weeks overall)
measure: 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
timeFrame: FU Week 24 (up to 72 weeks overall)
measure: Percentage of Participants With HBV DNA <2,000 IU/mL at 24 Weeks After EOT/POP in Groups A and B
timeFrame: FU Week 24 (up to 72 weeks overall)
measure: 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
timeFrame: FU Week 24 (up to 72 weeks overall)
measure: 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
timeFrame: FU Week 24 (up to 72 weeks overall)
measure: Percentage of Participants With HBeAg Seroconversion at EOT/POP in Groups A and B
timeFrame: Week 48
measure: Percentage of Participants With Loss of HBeAg at EOT/POP in Groups A and B
timeFrame: Week 48
measure: Percentage of Participants With HBsAg Seroconversion at EOT/POP in Groups A and B
timeFrame: Week 48
measure: Percentage of Participants With Loss of HBsAg at EOT/POP in Groups A and B
timeFrame: Week 48
measure: Percentage of Participants With Normal ALT at EOT/POP in Groups A and B
timeFrame: Week 48
measure: Percentage of Participants With HBV DNA <20,000 IU/mL at EOT/POP in Groups A and B
timeFrame: Week 48
measure: Percentage of Participants With HBV DNA <2,000 IU/mL at EOT/POP in Groups A and B
timeFrame: Week 48
measure: Percentage of Participants With HBV DNA Undetectable at EOT/POP in Groups A and B
timeFrame: Week 48
measure: Percentage of Participants With Combined HBeAg Seroconversion and HBV DNA <20,000 IU/mL at EOT/POP in Groups A and B
timeFrame: Week 48
measure: Percentage of Participants With Combined HBeAg Seroconversion and HBV DNA <2,000 IU/mL at EOT/POP in Groups A and B
timeFrame: Week 48
measure: Quantitative Serum ALT Level in Groups A and B
timeFrame: Baseline; Weeks 1, 2, 4, 8, 12, 18, 24, 30, 36, 42, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall)
measure: Quantitative HBV DNA Level in Groups A and B
timeFrame: Baseline; Weeks 12, 24, 36, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall)
measure: Change From Baseline in Quantitative HBV DNA Level in Groups A and B
timeFrame: Weeks 12, 24, 36, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall)
measure: Percentage of Participants With Loss of HBeAg at 24 Weeks After EOT in Group C
timeFrame: FU Week 24 (up to 72 weeks overall)
measure: Percentage of Participants With HBsAg Seroconversion at 24 Weeks After EOT in Group C
timeFrame: FU Week 24 (up to 72 weeks overall)
measure: Percentage of Participants With Loss of HBsAg at 24 Weeks After EOT in Group C
timeFrame: FU Week 24 (up to 72 weeks overall)
measure: Percentage of Participants With Normal ALT at 24 Weeks After EOT in Group C
timeFrame: FU Week 24 (up to 72 weeks overall)
measure: Percentage of Participants With HBV DNA <20,000 IU/mL at 24 Weeks After EOT in Group C
timeFrame: FU Week 24 (up to 72 weeks overall)
measure: Percentage of Participants With HBV DNA <2,000 IU/mL at 24 Weeks After EOT in Group C
timeFrame: FU Week 24 (up to 72 weeks overall)
measure: Percentage of Participants With HBV DNA Undetectable at 24 Weeks After EOT in Group C
timeFrame: FU Week 24 (up to 72 weeks overall)
measure: Percentage of Participants With Combined HBeAg Seroconversion and HBV DNA <20,000 IU/mL at 24 Weeks After EOT in Group C
timeFrame: FU Week 24 (up to 72 weeks overall)
measure: Percentage of Participants With Combined HBeAg Seroconversion and HBV DNA <2,000 IU/mL at 24 Weeks After EOT in Group C
timeFrame: FU Week 24 (up to 72 weeks overall)
measure: Percentage of Participants With HBeAg Seroconversion at EOT in Group C
timeFrame: Week 48
measure: Percentage of Participants With Loss of HBeAg at EOT in Group C
timeFrame: Week 48
measure: Percentage of Participants With HBsAg Seroconversion at EOT in Group C
timeFrame: Week 48
measure: Percentage of Participants With Loss of HBsAg at EOT in Group C
timeFrame: Week 48
measure: Percentage of Participants With Normal ALT at EOT in Group C
timeFrame: Week 48
measure: Percentage of Participants With HBV DNA <20,000 IU/mL at EOT in Group C
timeFrame: Week 48
measure: Percentage of Participants With HBV DNA <2,000 IU/mL at EOT in Group C
timeFrame: Week 48
measure: Percentage of Participants With HBV DNA Undetectable at EOT in Group C
timeFrame: Week 48
measure: Percentage of Participants With Combined HBeAg Seroconversion and HBV DNA <20,000 IU/mL at EOT in Group C
timeFrame: Week 48
measure: Percentage of Participants With Combined HBeAg Seroconversion and HBV DNA <2,000 IU/mL at EOT in Group C
timeFrame: Week 48
measure: Quantitative Serum ALT Level in Group C
timeFrame: Baseline; Weeks 1, 2, 4, 8, 12, 18, 24, 30, 36, 42, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall)
measure: Quantitative HBV DNA Level in Group C
timeFrame: Baseline; Weeks 12, 24, 36, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall)
measure: Change From Baseline in Quantitative HBV DNA Level in Group C
timeFrame: Weeks 12, 24, 36, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall)
measure: Estimated Area Under the Concentration-Time Curve (AUC) by BSA Category
timeFrame: 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)
measure: Percentage of Participants With >15% Drop in Height Percentile for Age in Groups A and B
timeFrame: Weeks 12, 24, 36, 48; FU Weeks 12, 24 (up to 72 weeks overall)
measure: Percentage of Participants With >15% Drop in Weight Percentile for Age in Groups A and B
timeFrame: Weeks 4, 8, 12, 18, 24, 30, 36, 42, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall)
measure: Quantitative HBeAg Level in Groups A and B
timeFrame: Baseline; Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall)
measure: Quantitative HBsAg Level in Groups A and B
timeFrame: Baseline; Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall)
measure: Quantitative HBeAg Level in Group C
timeFrame: Baseline; Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall)
measure: Quantitative HBsAg Level in Group C
timeFrame: Baseline; Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall)
measure: Change From Baseline in Liver Stiffness Measure (LSM) in Groups A, B, C
timeFrame: Week 48; FU Week 24 (up to 72 weeks overall)
measure: Percentage of Participants With >15% Drop in Height Percentile for Age in Group C
timeFrame: Weeks 30, 36; FU Weeks 4, 12, 24 (up to 72 weeks overall)
measure: Change From Baseline in Height for Age Z-Score in Groups A and B
timeFrame: Baseline; Weeks 12, 24, 36, 48; FU Weeks 12, 24 (up to 72 weeks overall)
measure: Change From Baseline in Weight for Age Z-Score in Groups A and B
timeFrame: Baseline; Weeks 1, 2, 4, 8, 12, 18, 24, 30, 36, 42, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall)
measure: Change From Baseline in Height for Age Z-Score in Group C
timeFrame: Baseline; Weeks 12, 24, 36, 48; FU Weeks 12, 24 (up to 72 weeks overall)
measure: Change From Baseline in Weight for Age Z-Score in Group C
timeFrame: Baseline; Weeks 1, 2, 4, 8, 12, 18, 24, 30, 36, 42, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall)
measure: Percentage of Participants With HBeAg Seroconversion at 24 Weeks After EOT in Group C
timeFrame: FU Week 24 (up to 72 weeks overall)
measure: Change From Baseline in Quantitative Serum ALT Level in Groups A and B
timeFrame: Weeks 1, 2, 4, 8, 12, 18, 24, 30, 36, 42, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall)
measure: Change From Baseline in Quantitative HBeAg Level in Groups A and B
timeFrame: Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall)
measure: Change From Baseline in Quantitative HBsAg Level in Groups A and B
timeFrame: Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall)
measure: Change From Baseline in Quantitative Serum ALT Level in Group C
timeFrame: Weeks 1, 2, 4, 8, 12, 18, 24, 30, 36, 42, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall)
measure: Change From Baseline in Quantitative HBeAg Level in Group C
timeFrame: Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall)
measure: Change From Baseline in Quantitative HBsAg Level in Group C
timeFrame: Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall)
measure: Percentage of Participants With HBeAg Seroconversion Over Time in Groups A and B
timeFrame: Baseline, FU Years: 1, 2, 3, 4, 5
measure: Percentage of Participants With Loss of HBeAg at 24 Weeks After the End of Switch Treatment Period: Switch Group
timeFrame: FU Week 24 (up to 72 weeks overall)
measure: Percentage of Participants With HBsAg Seroconversion at 24 Weeks After the End of Switch Treatment Period: Switch Group
timeFrame: FU Week 24 (up to 72 weeks overall)
measure: Percentage of Participants With Loss of HBsAg at 24 Weeks After the End of Switch Treatment Period: Switch Group
timeFrame: FU Week 24 (up to 72 weeks overall)
measure: Percentage of Participants With Normal ALT at 24 Weeks After the End of Switch Treatment Period: Switch Group
timeFrame: FU Week 24 (up to 72 weeks overall)
measure: 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
timeFrame: FU Week 24 (up to 72 weeks overall)
measure: Percentage of Participants With HBV DNA <2,000 IU/mL at 24 Weeks After the End of Switch Treatment Period: Switch Group
timeFrame: FU Week 24 (up to 72 weeks overall)
measure: Percentage of Participants With HBV DNA Undetectable at 24 Weeks After the End of Switch Treatment Period: Switch Group
timeFrame: FU Week 24 (up to 72 weeks overall)
measure: 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
timeFrame: FU Week 24 (up to 72 weeks overall)
measure: 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
timeFrame: FU Week 24 (up to 72 weeks overall)
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: Univ of California SF, Benioff Children's Hospital; Pediatrics, Gastro, Hepatology & Nutrition
state: California
city: Baltimore
country: United States
facility: Johns Hopkins Hospital - Pediatric Gastroenterology
state: Maryland
city: Boston
country: United States
facility: Children's Hospital Boston-Harvard Medical School; Division of Gastoenterology
state: Massachusetts
city: Saint Louis
country: United States
facility: St. Louis University - Cardinal Glennon Children's Medical Center
state: Missouri
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: North Adelaide
country: Australia
facility: Womens and Childrens Hospital; Department of Gastroenterology
state: South Australia
city: Melbourne
country: Australia
facility: Royal Children's Hospital; Department of Gastroenterology
state: Victoria
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires St-Luc
city: Gent
country: Belgium
facility: UZ Gent
city: Sofia
country: Bulgaria
facility: Specialized Hospital for Active Treatment of Pediatrics Diseases; Clinic of Gastroenterology
city: Varna
country: Bulgaria
facility: University Hospital "St. Marine"; Dept. of Pediatrics
city: Beijing City
country: China
facility: Beijing You An Hospital; Digestive Dept
city: Beijing
country: China
facility: Beijing 302 Hospital; No. 2 Infectious Disease Section
city: Changchun
country: China
facility: the First Hospital of Jilin University
city: Chongqing
country: China
facility: Southwest Hospital , Third Military Medical University
city: Guangzhou
country: China
facility: The Eighth People's Hospital of Guangzhou
city: Guangzhou
country: China
facility: The Third Affiliated Hospital of Sun Yat-Sen University
city: Kunming
country: China
facility: The First Affilliated Hospital of Kunming Medical College
city: Urumqi (乌鲁木齐)
country: China
facility: Xinjiang Uygur Autonomous Region Hospital of Chinese Traditional Medicine
city: Wuhan
country: China
facility: Tongji Hosp, Tongji Med. Col, Huazhong Univ. of Sci. & Tech
city: Xi'an
country: China
facility: First Affiliated Hospital of Medical College of Xi'an Jiaotong University
city: Wuppertal
country: Germany
facility: HELIOS Klinikum Wuppertal, Zentrum für Kinder- und Jugendmedizin, Universität Witten-Herdecke
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Jerusalem
country: Israel
facility: Hadassah University Hospital - Ein Kerem
city: Nahariya
country: Israel
facility: Western Galilee Hospital - Nahariya
city: Bologna
country: Italy
facility: Uni Degli Studi Di Bologna - Policlinica S. Orsola; Inst. Di Malattie Infettive
state: Emilia-Romagna
city: Bydgoszcz
country: Poland
facility: Wojewodzki Szpital Obserwacyjno-Zakazny; Oddział Pediatrii, Chorób Infekcyjnych i Hepatologii
city: Krakow
country: Poland
facility: Krakowski Szpital Specjalistyczny im Jana Pawła II; Oddział Chorób Infekcyjnych Dzieci
city: Łodz
country: Poland
facility: Wojewodzki Specjalistyczny Szpital im. Dr W.Bieganskiego; Oddział Obserwacyjno-Zakażny dla Dzieci
city: Moscow
country: Russian Federation
facility: SFI Sceintific Research institute of nutrition of RAMS
city: Moscow
country: Russian Federation
facility: SI Sceintific children health center RAMS
city: Saint Petersburg
country: Russian Federation
facility: FSI Scientific research Institute of children's infections
city: Samara
country: Russian Federation
facility: MC Gepatolog
city: Kyiv
country: Ukraine
facility: Kyiv Children's Clinical Infectious Diseases Hospital
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: London
country: United Kingdom
facility: Kings College Hospital NHS Foundation Trust
city: London
country: United Kingdom
facility: Imperial College Healthcare Trust
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.