A Study of Pegasys (Peginterferon Alfa-2a [PEG-IFN]) Versus Untreated Control in Children With Hepatitis B Envelope Antigen (HBeAg)-Positive Chronic Hepatitis B

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01519960
First received: December 6, 2011
Last updated: July 8, 2016
Last verified: July 2016
  Purpose
This parallel-group, open-label study will evaluate the safety and efficacy of Pegasys (PEG-IFN) versus untreated control in children aged 3 to less than (<) 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 PEG-IFN 45 to 180 micrograms (mcg) subcutaneously once weekly for 48 weeks, or to the untreated control Group B. Children with advanced fibrosis will be assigned to treatment Group C to receive 48 weeks of treatment with PEG-IFN. Children in the untreated control Group B who have not experienced seroconversion 48 weeks after randomization may enter the switch arm Group D to receive 48 weeks of PEG-IFN treatment. This offer will be available for 1 year following 48 weeks from randomization. Anticipated time on study treatment is 48 weeks. All participants will be followed up for 5 years after the end of treatment (in Groups A, C, D)/principal observation period (in Group B).

Condition Intervention Phase
Hepatitis B, Chronic
Drug: Peginterferon alfa-2a
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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 in the Immune Active Phase

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Percentage of Participants With HBeAg Seroconversion at 24 Weeks After End of Treatment (EOT)/POP in Groups A and B [ Time Frame: FU Week 24 (up to 72 weeks overall) ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Percentage of Participants With Loss of HBeAg at 24 Weeks After EOT/POP in Groups A and B [ Time Frame: FU Week 24 (up to 72 weeks overall) ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Seroconversion at 24 Weeks After EOT/POP in Groups A and B [ Time Frame: FU Week 24 (up to 72 weeks overall) ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Loss of HBsAg at 24 Weeks After EOT/POP in Groups A and B [ Time Frame: FU Week 24 (up to 72 weeks overall) ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Normal ALT at 24 Weeks After EOT/POP in Groups A and B [ Time Frame: FU Week 24 (up to 72 weeks overall) ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: FU Week 24 (up to 72 weeks overall) ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With HBV DNA <2,000 IU/mL at 24 Weeks After EOT/POP in Groups A and B [ Time Frame: FU Week 24 (up to 72 weeks overall) ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With HBV DNA Undetectable at 24 Weeks After EOT/POP in Groups A and B [ Time Frame: FU Week 24 (up to 72 weeks overall) ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: FU Week 24 (up to 72 weeks overall) ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: FU Week 24 (up to 72 weeks overall) ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With HBeAg Seroconversion at EOT/POP in Groups A and B [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Loss of HBeAg at EOT/POP in Groups A and B [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    The percentage of participants with loss of HBeAg at EOT/POP was reported. The 95% CI was calculated by the Pearson-Clopper method.

  • Percentage of Participants With HBsAg Seroconversion at EOT/POP in Groups A and B [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Loss of HBsAg at EOT/POP in Groups A and B [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    The percentage of participants with loss of HBsAg at EOT/POP was reported. The 95% CI was calculated by the Pearson-Clopper method.

  • Percentage of Participants With Normal ALT at EOT/POP in Groups A and B [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With HBV DNA <20,000 IU/mL at EOT/POP in Groups A and B [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With HBV DNA <2,000 IU/mL at EOT/POP in Groups A and B [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With HBV DNA Undetectable at EOT/POP in Groups A and B [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Combined HBeAg Seroconversion and HBV DNA <20,000 IU/mL at EOT/POP in Groups A and B [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Combined HBeAg Seroconversion and HBV DNA <2,000 IU/mL at EOT/POP in Groups A and B [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    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.

  • Quantitative Serum ALT Level in Groups A and B [ Time Frame: Baseline; Weeks 1, 2, 4, 8, 12, 18, 24, 30, 36, 42, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall) ] [ Designated as safety issue: No ]
    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).

  • Quantitative HBV DNA Level in Groups A and B [ Time Frame: Baseline; Weeks 12, 24, 36, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall) ] [ Designated as safety issue: No ]
    Quantitative HBV DNA at each visit was averaged among all participants and expressed in log10 IU/mL.

  • Change From Baseline in Quantitative HBV DNA Level in Groups A and B [ Time Frame: Weeks 12, 24, 36, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall) ] [ Designated as safety issue: No ]
    The change in quantitative HBV DNA from Baseline to each visit was averaged among all participants and expressed in log10 IU/mL.

  • Percentage of Participants With Loss of HBeAg at 24 Weeks After EOT in Group C [ Time Frame: FU Week 24 (up to 72 weeks overall) ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With HBsAg Seroconversion at 24 Weeks After EOT in Group C [ Time Frame: FU Week 24 (up to 72 weeks overall) ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Loss of HBsAg at 24 Weeks After EOT in Group C [ Time Frame: FU Week 24 (up to 72 weeks overall) ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Normal ALT at 24 Weeks After EOT in Group C [ Time Frame: FU Week 24 (up to 72 weeks overall) ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With HBV DNA <20,000 IU/mL at 24 Weeks After EOT in Group C [ Time Frame: FU Week 24 (up to 72 weeks overall) ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With HBV DNA <2,000 IU/mL at 24 Weeks After EOT in Group C [ Time Frame: FU Week 24 (up to 72 weeks overall) ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With HBV DNA Undetectable at 24 Weeks After EOT in Group C [ Time Frame: FU Week 24 (up to 72 weeks overall) ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Combined HBeAg Seroconversion and HBV DNA <20,000 IU/mL at 24 Weeks After EOT in Group C [ Time Frame: FU Week 24 (up to 72 weeks overall) ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Combined HBeAg Seroconversion and HBV DNA <2,000 IU/mL at 24 Weeks After EOT in Group C [ Time Frame: FU Week 24 (up to 72 weeks overall) ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With HBeAg Seroconversion at EOT in Group C [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Loss of HBeAg at EOT in Group C [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    The percentage of participants with loss of HBeAg at EOT was reported. The 95% CI was calculated by the Pearson-Clopper method.

  • Percentage of Participants With HBsAg Seroconversion at EOT in Group C [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Loss of HBsAg at EOT in Group C [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    The percentage of participants with loss of HBsAg at EOT was reported. The 95% CI was calculated by the Pearson-Clopper method.

  • Percentage of Participants With Normal ALT at EOT in Group C [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With HBV DNA <20,000 IU/mL at EOT in Group C [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With HBV DNA <2,000 IU/mL at EOT in Group C [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With HBV DNA Undetectable at EOT in Group C [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Combined HBeAg Seroconversion and HBV DNA <20,000 IU/mL at EOT in Group C [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Combined HBeAg Seroconversion and HBV DNA <2,000 IU/mL at EOT in Group C [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    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.

  • Quantitative Serum ALT Level in Group C [ Time Frame: Baseline; Weeks 1, 2, 4, 8, 12, 18, 24, 30, 36, 42, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall) ] [ Designated as safety issue: No ]
    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).

  • Quantitative HBV DNA Level in Group C [ Time Frame: Baseline; Weeks 12, 24, 36, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall) ] [ Designated as safety issue: No ]
    Quantitative HBV DNA at each visit was averaged among all participants and expressed in log10 IU/mL.

  • Change From Baseline in Quantitative HBV DNA Level in Group C [ Time Frame: Weeks 12, 24, 36, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall) ] [ Designated as safety issue: No ]
    The change in quantitative HBV DNA from Baseline to each visit was averaged among all participants and expressed in log10 IU/mL.

  • Change From Baseline in Liver Stiffness Measure (LSM) in Groups A, B, C [ Time Frame: Baseline; Week 48; FU Week 24 (up to 72 weeks overall) ] [ Designated as safety issue: No ]
    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.

  • Estimated Area Under the Concentration-Time Curve (AUC) by BSA Category [ Time Frame: 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) ] [ Designated as safety issue: No ]
    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).

  • Percentage of Participants With >15% Drop in Height Percentile for Age in Groups A and B [ Time Frame: Weeks 12, 24, 36, 48; FU Weeks 12, 24 (up to 72 weeks overall) ] [ Designated as safety issue: Yes ]
    The percentage of participants with >15% drop in height percentile for age from Baseline to each visit was reported.

  • Percentage of Participants With >15% Drop in Weight Percentile for Age in Groups A and B [ Time Frame: Weeks 4, 8, 12, 18, 24, 30, 36, 42, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall) ] [ Designated as safety issue: Yes ]
    The percentage of participants with >15% drop in weight percentile for age from Baseline to each visit was reported.

  • Percentage of Participants With >15% Drop in Height Percentile for Age in Group C [ Time Frame: Weeks 12, 24, 48; FU Week 24 (up to 72 weeks overall) ] [ Designated as safety issue: Yes ]
    The percentage of participants with >15% drop in height percentile for age from Baseline to each visit was reported.

  • Percentage of Participants With >15% Drop in Weight Percentile for Age in Group C [ Time Frame: Weeks 30, 36; FU Weeks 4, 12, 24 (up to 72 weeks overall) ] [ Designated as safety issue: Yes ]
    The percentage of participants with >15% drop in weight percentile for age from Baseline to each visit was reported.

  • Change From Baseline in Height for Age Z-Score in Groups A and B [ Time Frame: Baseline; Weeks 12, 24, 36, 48; FU Weeks 12, 24 (up to 72 weeks overall) ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Weight for Age Z-Score in Groups A and B [ Time Frame: Baseline; Weeks 1, 2, 4, 8, 12, 18, 24, 30, 36, 42, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall) ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Height for Age Z-Score in Group C [ Time Frame: Baseline; Weeks 12, 24, 36, 48; FU Weeks 12, 24 (up to 72 weeks overall) ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Weight for Age Z-Score in Group C [ Time Frame: Baseline; Weeks 1, 2, 4, 8, 12, 18, 24, 30, 36, 42, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall) ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With HBeAg Seroconversion at 24 Weeks After EOT in Group C [ Time Frame: FU Week 24 (up to 72 weeks overall) ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Quantitative Serum ALT Level in Groups A and B [ Time Frame: Weeks 1, 2, 4, 8, 12, 18, 24, 30, 36, 42, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall) ] [ Designated as safety issue: No ]
    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).

  • Quantitative HBeAg Level in Groups A and B [ Time Frame: Baseline; Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall) ] [ Designated as safety issue: No ]
    Quantitative HBeAg at each visit was averaged among all participants and expressed in log10 Paul Ehrlich Institute units per milliliter (PEIU/mL).

  • Change From Baseline in Quantitative HBeAg Level in Groups A and B [ Time Frame: Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall) ] [ Designated as safety issue: No ]
    The change in quantitative HBeAg from Baseline to each visit was averaged among all participants and expressed in log10 PEIU/mL.

  • Quantitative HBsAg Level in Groups A and B [ Time Frame: Baseline; Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall) ] [ Designated as safety issue: No ]
    Quantitative HBsAg at each visit was averaged among all participants and expressed in log10 IU/mL.

  • Change From Baseline in Quantitative HBsAg Level in Groups A and B [ Time Frame: Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall) ] [ Designated as safety issue: No ]
    The change in quantitative HBsAg from Baseline to each visit was averaged among all participants and expressed in log10 IU/mL.

  • Change From Baseline in Quantitative Serum ALT Level in Group C [ Time Frame: Weeks 1, 2, 4, 8, 12, 18, 24, 30, 36, 42, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall) ] [ Designated as safety issue: No ]
    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).

  • Quantitative HBeAg Level in Group C [ Time Frame: Baseline; Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall) ] [ Designated as safety issue: No ]
    Quantitative HBeAg at each visit was averaged among all participants and expressed in log10 PEIU/mL.

  • Change From Baseline in Quantitative HBeAg Level in Group C [ Time Frame: Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall) ] [ Designated as safety issue: No ]
    The change in quantitative HBeAg from Baseline to each visit was averaged among all participants and expressed in log10 PEIU/mL.

  • Quantitative HBsAg Level in Group C [ Time Frame: Baseline; Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall) ] [ Designated as safety issue: No ]
    Quantitative HBsAg at each visit was averaged among all participants and expressed in log10 IU/mL.

  • Change From Baseline in Quantitative HBsAg Level in Group C [ Time Frame: Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall) ] [ Designated as safety issue: No ]
    The change in quantitative HBsAg from Baseline to each visit was averaged among all participants and expressed in log10 IU/mL.


Enrollment: 161
Study Start Date: July 2012
Estimated Study Completion Date: August 2022
Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group A: PEG-IFN Monotherapy Without Advanced Fibrosis
Participants without advanced fibrosis will be randomized to receive PEG-IFN monotherapy (45 to 180 mcg per week subcutaneously) for 48 weeks with a 5-year follow-up.
Drug: Peginterferon alfa-2a
Each dose of 45 to 180 mcg will be based on body surface area (BSA) and given as a once-weekly subcutaneous injection for 48 weeks. BSA-based dosing is as follows: 0.51-0.53 m^2, 45 mcg; 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.
Other Name: Pegasys
No Intervention: Group B: Untreated Control Without Advanced Fibrosis
Participants without advanced fibrosis will be randomized and evaluated for 48 weeks with a 5-year follow-up. As the study is open-label, participants will not receive any investigational or placebo treatment during the 48-week principal observation period. The same PEG-IFN regimen administered in Group A (45 to 180 mcg per week subcutaneously) will be offered to participants in Group B who have not experienced HBeAg seroconversion. The offer will remain for up to 1 year.
Experimental: Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Participants with advanced fibrosis will be allocated (not randomized) to receive PEG-IFN monotherapy (45 to 180 mcg per week subcutaneously) for 48 weeks with a 5-year follow-up.
Drug: Peginterferon alfa-2a
Each dose of 45 to 180 mcg will be based on body surface area (BSA) and given as a once-weekly subcutaneous injection for 48 weeks. BSA-based dosing is as follows: 0.51-0.53 m^2, 45 mcg; 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.
Other Name: Pegasys
Experimental: Group D: Switch to PEG-IFN Monotherapy
Participants without advanced fibrosis who do not receive treatment and have not experienced HBeAg seroconversion will be allowed to switch to PEG-IFN monotherapy (45 to 180 mcg per week subcutaneously). Treatment will be given over 48 weeks with a 5-year follow-up.
Drug: Peginterferon alfa-2a
Each dose of 45 to 180 mcg will be based on body surface area (BSA) and given as a once-weekly subcutaneous injection for 48 weeks. BSA-based dosing is as follows: 0.51-0.53 m^2, 45 mcg; 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.
Other Name: Pegasys

  Eligibility

Ages Eligible for Study:   3 Years to 17 Years   (Child)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Males or females 3 to <18 years of age at Baseline
  • Positive HBsAg for more than 6 months
  • Positive HBeAg and detectable hepatitis B virus (HBV) DNA at Screening
  • A liver biopsy obtained within the past 2 years prior to Baseline to confirm the presence of advanced fibrosis or exclude cirrhosis
  • Compensated liver disease (Child-Pugh Class A)
  • Elevated serum alanine aminotransferase (ALT) > upper limit of normal (ULN) but ≤ 10 × ULN

Exclusion Criteria:

  • Cirrhosis
  • Investigational drugs or licensed treatments with anti-HBV activity within 6 months prior to Baseline
  • Known hypersensitivity to PEG-IFN
  • Positive test results at screening for hepatitis A, hepatitis C, hepatitis D, or human immunodeficiency virus (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 (Child-Pugh Class B or C or clinical evidence such as ascites or varices)
  • History of immunologically mediated disease
  • Pregnant or lactating females
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01519960

  Hide Study Locations
Locations
United States, California
San Francisco, California, United States, 94143
United States, Maryland
Baltimore, Maryland, United States, 21287-5554
United States, Massachusetts
Boston, Massachusetts, United States, 02115
United States, Missouri
St. Louis, Missouri, United States, 63104
United States, Texas
Houston, Texas, United States, 77030
United States, Washington
Seattle, Washington, United States, 98105
Australia, New South Wales
Sydney, New South Wales, Australia, 2145
Australia, South Australia
North Adelaide, South Australia, Australia, 5006
Australia, Victoria
Melbourne, Victoria, Australia, 3053
Belgium
Bruxelles, Belgium, 1200
Gent, Belgium, 9000
Bulgaria
Sofia, Bulgaria, 1612
Varna, Bulgaria, 9000
China
Beijing, China, 100039
Beijing, China, 100069
Changchun, China, 130021
Chongqing, China, 400038
Guangzhou, China, 510060
Guangzhou, China, 510630
Kunming, China, 650032
Shanghai, China, 200235
Urumqi (乌鲁木齐), China, 830000
Wuhan, China, 430030
Xi'an, China, 710061
Germany
Wuppertal, Germany, 42283
Israel
Haifa, Israel, 31096
Jerusalem, Israel, 9112001
Nahariya, Israel, 22100
Italy
Bologna, Emilia-Romagna, Italy, 40138
Torino, Piemonte, Italy, 10126
Poland
Bydgoszcz, Poland, 85-030
Krakow, Poland, 31-202
Poznan, Poland, 60-693
Łodz, Poland, 91-347
Russian Federation
Arkhangelsk, Russian Federation, 163045
Moscow, Russian Federation, 115446
Moscow, Russian Federation, 119991
Saint Petersburg, Russian Federation, 197022
Samara, Russian Federation, 443100
Ukraine
Kyiv, Ukraine, 01119
Kyiv, Ukraine, 04050
United Kingdom
Birmingham, United Kingdom, B4 6NH
London, United Kingdom, SE5 9RS
London, United Kingdom, W2 1PG
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01519960     History of Changes
Other Study ID Numbers: YV25718  2011-002732-70 
Study First Received: December 6, 2011
Results First Received: July 8, 2016
Last Updated: July 8, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis, Chronic
Hepatitis B
Hepatitis B, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Peginterferon alfa-2a
Interferon-alpha
Antiviral Agents
Anti-Infective Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 29, 2016