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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01519960




Registration number
NCT01519960
Ethics application status
Date submitted
6/12/2011
Date registered
27/01/2012
Date last updated
23/06/2020

Titles & IDs
Public title
A Study of Pegasys (Peginterferon Alfa-2a) Versus Untreated Control in Children With HBeAg Positive Chronic Hepatitis B
Scientific 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
Secondary ID [1] 0 0
2011-002732-70
Secondary ID [2] 0 0
YV25718
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hepatitis B, Chronic 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - peginterferon alfa-2a [Pegasys]
Treatment: Drugs - peginterferon alfa-2a [Pegasys]

Experimental: A Pegasys -

No Intervention: B Untreated Control -

Experimental: C Fibrosis non-randomized -

Experimental: Switch -


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

Treatment: Drugs: 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

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
FU Week 24 (up to 72 weeks overall)
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
FU Week 24 (up to 72 weeks overall)
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
FU Week 24 (up to 72 weeks overall)
Secondary outcome [3] 0 0
Percentage of Participants With Loss of HBsAg at 24 Weeks After EOT/POP in Groups A and B - The percentage of participants with loss of HBsAg at 24 weeks after EOT/POP was reported. The 95% CI was calculated by the Pearson-Clopper method.
Timepoint [3] 0 0
FU Week 24 (up to 72 weeks overall)
Secondary outcome [4] 0 0
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.
Timepoint [4] 0 0
FU Week 24 (up to 72 weeks overall)
Secondary outcome [5] 0 0
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.
Timepoint [5] 0 0
FU Week 24 (up to 72 weeks overall)
Secondary outcome [6] 0 0
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.
Timepoint [6] 0 0
FU Week 24 (up to 72 weeks overall)
Secondary outcome [7] 0 0
Percentage of Participants With HBV DNA Undetectable at 24 Weeks After 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 24 weeks after EOT/POP was reported. The 95% CI was calculated by the Pearson-Clopper method.
Timepoint [7] 0 0
FU Week 24 (up to 72 weeks overall)
Secondary outcome [8] 0 0
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.
Timepoint [8] 0 0
FU Week 24 (up to 72 weeks overall)
Secondary outcome [9] 0 0
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.
Timepoint [9] 0 0
FU Week 24 (up to 72 weeks overall)
Secondary outcome [10] 0 0
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.
Timepoint [10] 0 0
Week 48
Secondary outcome [11] 0 0
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.
Timepoint [11] 0 0
Week 48
Secondary outcome [12] 0 0
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.
Timepoint [12] 0 0
Week 48
Secondary outcome [13] 0 0
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.
Timepoint [13] 0 0
Week 48
Secondary outcome [14] 0 0
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.
Timepoint [14] 0 0
Week 48
Secondary outcome [15] 0 0
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.
Timepoint [15] 0 0
Week 48
Secondary outcome [16] 0 0
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.
Timepoint [16] 0 0
Week 48
Secondary outcome [17] 0 0
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.
Timepoint [17] 0 0
Week 48
Secondary outcome [18] 0 0
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.
Timepoint [18] 0 0
Week 48
Secondary outcome [19] 0 0
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.
Timepoint [19] 0 0
Week 48
Secondary outcome [20] 0 0
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).
Timepoint [20] 0 0
Baseline; Weeks 1, 2, 4, 8, 12, 18, 24, 30, 36, 42, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall)
Secondary outcome [21] 0 0
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.
Timepoint [21] 0 0
Baseline; Weeks 12, 24, 36, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall)
Secondary outcome [22] 0 0
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.
Timepoint [22] 0 0
Weeks 12, 24, 36, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall)
Secondary outcome [23] 0 0
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.
Timepoint [23] 0 0
FU Week 24 (up to 72 weeks overall)
Secondary outcome [24] 0 0
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.
Timepoint [24] 0 0
FU Week 24 (up to 72 weeks overall)
Secondary outcome [25] 0 0
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.
Timepoint [25] 0 0
FU Week 24 (up to 72 weeks overall)
Secondary outcome [26] 0 0
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.
Timepoint [26] 0 0
FU Week 24 (up to 72 weeks overall)
Secondary outcome [27] 0 0
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.
Timepoint [27] 0 0
FU Week 24 (up to 72 weeks overall)
Secondary outcome [28] 0 0
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.
Timepoint [28] 0 0
FU Week 24 (up to 72 weeks overall)
Secondary outcome [29] 0 0
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.
Timepoint [29] 0 0
FU Week 24 (up to 72 weeks overall)
Secondary outcome [30] 0 0
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.
Timepoint [30] 0 0
FU Week 24 (up to 72 weeks overall)
Secondary outcome [31] 0 0
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.
Timepoint [31] 0 0
FU Week 24 (up to 72 weeks overall)
Secondary outcome [32] 0 0
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.
Timepoint [32] 0 0
Week 48
Secondary outcome [33] 0 0
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.
Timepoint [33] 0 0
Week 48
Secondary outcome [34] 0 0
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.
Timepoint [34] 0 0
Week 48
Secondary outcome [35] 0 0
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.
Timepoint [35] 0 0
Week 48
Secondary outcome [36] 0 0
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.
Timepoint [36] 0 0
Week 48
Secondary outcome [37] 0 0
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.
Timepoint [37] 0 0
Week 48
Secondary outcome [38] 0 0
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.
Timepoint [38] 0 0
Week 48
Secondary outcome [39] 0 0
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.
Timepoint [39] 0 0
Week 48
Secondary outcome [40] 0 0
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.
Timepoint [40] 0 0
Week 48
Secondary outcome [41] 0 0
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.
Timepoint [41] 0 0
Week 48
Secondary outcome [42] 0 0
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).
Timepoint [42] 0 0
Baseline; Weeks 1, 2, 4, 8, 12, 18, 24, 30, 36, 42, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall)
Secondary outcome [43] 0 0
Quantitative HBV DNA Level in Group C - Quantitative HBV DNA at each visit was averaged among all participants and expressed in log10 IU/mL.
Timepoint [43] 0 0
Baseline; Weeks 12, 24, 36, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall)
Secondary outcome [44] 0 0
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.
Timepoint [44] 0 0
Weeks 12, 24, 36, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall)
Secondary outcome [45] 0 0
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.
Timepoint [45] 0 0
Baseline; Week 48; FU Week 24 (up to 72 weeks overall)
Secondary outcome [46] 0 0
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).
Timepoint [46] 0 0
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 outcome [47] 0 0
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.
Timepoint [47] 0 0
Weeks 12, 24, 36, 48; FU Weeks 12, 24 (up to 72 weeks overall)
Secondary outcome [48] 0 0
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.
Timepoint [48] 0 0
Weeks 4, 8, 12, 18, 24, 30, 36, 42, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall)
Secondary outcome [49] 0 0
Percentage of Participants With >15% Drop in Height Percentile for Age in Group C - The percentage of participants with >15% drop in height percentile for age from Baseline to each visit was reported.
Timepoint [49] 0 0
Weeks 12, 24, 48; FU Week 24 (up to 72 weeks overall)
Secondary outcome [50] 0 0
Percentage of Participants With >15% Drop in Weight 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.
Timepoint [50] 0 0
Weeks 30, 36; FU Weeks 4, 12, 24 (up to 72 weeks overall)
Secondary outcome [51] 0 0
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.
Timepoint [51] 0 0
Baseline; Weeks 12, 24, 36, 48; FU Weeks 12, 24 (up to 72 weeks overall)
Secondary outcome [52] 0 0
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.
Timepoint [52] 0 0
Baseline; Weeks 1, 2, 4, 8, 12, 18, 24, 30, 36, 42, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall)
Secondary outcome [53] 0 0
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.
Timepoint [53] 0 0
Baseline; Weeks 12, 24, 36, 48; FU Weeks 12, 24 (up to 72 weeks overall)
Secondary outcome [54] 0 0
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.
Timepoint [54] 0 0
Baseline; Weeks 1, 2, 4, 8, 12, 18, 24, 30, 36, 42, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall)
Secondary outcome [55] 0 0
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.
Timepoint [55] 0 0
FU Week 24 (up to 72 weeks overall)
Secondary outcome [56] 0 0
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).
Timepoint [56] 0 0
Weeks 1, 2, 4, 8, 12, 18, 24, 30, 36, 42, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall)
Secondary outcome [57] 0 0
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).
Timepoint [57] 0 0
Baseline; Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall)
Secondary outcome [58] 0 0
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.
Timepoint [58] 0 0
Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall)
Secondary outcome [59] 0 0
Quantitative HBsAg Level in Groups A and B - Quantitative HBsAg at each visit was averaged among all participants and expressed in log10 IU/mL.
Timepoint [59] 0 0
Baseline; Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall)
Secondary outcome [60] 0 0
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.
Timepoint [60] 0 0
Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall)
Secondary outcome [61] 0 0
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).
Timepoint [61] 0 0
Weeks 1, 2, 4, 8, 12, 18, 24, 30, 36, 42, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall)
Secondary outcome [62] 0 0
Quantitative HBeAg Level in Group C - Quantitative HBeAg at each visit was averaged among all participants and expressed in log10 PEIU/mL.
Timepoint [62] 0 0
Baseline; Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall)
Secondary outcome [63] 0 0
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.
Timepoint [63] 0 0
Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall)
Secondary outcome [64] 0 0
Quantitative HBsAg Level in Group C - Quantitative HBsAg at each visit was averaged among all participants and expressed in log10 IU/mL.
Timepoint [64] 0 0
Baseline; Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall)
Secondary outcome [65] 0 0
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.
Timepoint [65] 0 0
Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall)

Eligibility
Key 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
Minimum age
3 Years
Maximum age
17 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA,VIC
Recruitment hospital [1] 0 0
Womens and Childrens Hospital; Department of Gastroenterology - North Adelaide
Recruitment hospital [2] 0 0
Royal Children's Hospital; Department of Gastroenterology - Melbourne
Recruitment postcode(s) [1] 0 0
5006 - North Adelaide
Recruitment postcode(s) [2] 0 0
3053 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Maryland
Country [3] 0 0
United States of America
State/province [3] 0 0
Massachusetts
Country [4] 0 0
United States of America
State/province [4] 0 0
Missouri
Country [5] 0 0
United States of America
State/province [5] 0 0
Texas
Country [6] 0 0
United States of America
State/province [6] 0 0
Washington
Country [7] 0 0
Belgium
State/province [7] 0 0
Bruxelles
Country [8] 0 0
Belgium
State/province [8] 0 0
Gent
Country [9] 0 0
Bulgaria
State/province [9] 0 0
Sofia
Country [10] 0 0
Bulgaria
State/province [10] 0 0
Varna
Country [11] 0 0
China
State/province [11] 0 0
Beijing
Country [12] 0 0
China
State/province [12] 0 0
Changchun
Country [13] 0 0
China
State/province [13] 0 0
Chongqing
Country [14] 0 0
China
State/province [14] 0 0
Guangzhou
Country [15] 0 0
China
State/province [15] 0 0
Kunming
Country [16] 0 0
China
State/province [16] 0 0
Urumqi (????)
Country [17] 0 0
China
State/province [17] 0 0
Wuhan
Country [18] 0 0
China
State/province [18] 0 0
Xi'an
Country [19] 0 0
Germany
State/province [19] 0 0
Wuppertal
Country [20] 0 0
Israel
State/province [20] 0 0
Haifa
Country [21] 0 0
Israel
State/province [21] 0 0
Jerusalem
Country [22] 0 0
Israel
State/province [22] 0 0
Nahariya
Country [23] 0 0
Italy
State/province [23] 0 0
Emilia-Romagna
Country [24] 0 0
Poland
State/province [24] 0 0
Bydgoszcz
Country [25] 0 0
Poland
State/province [25] 0 0
Krakow
Country [26] 0 0
Poland
State/province [26] 0 0
Lodz
Country [27] 0 0
Russian Federation
State/province [27] 0 0
Moscow
Country [28] 0 0
Russian Federation
State/province [28] 0 0
Saint Petersburg
Country [29] 0 0
Russian Federation
State/province [29] 0 0
Samara
Country [30] 0 0
Ukraine
State/province [30] 0 0
Kyiv
Country [31] 0 0
United Kingdom
State/province [31] 0 0
Birmingham
Country [32] 0 0
United Kingdom
State/province [32] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT01519960
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications