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
Results First Received: July 8, 2016  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Hepatitis B, Chronic
Intervention: Drug: Peginterferon alfa-2a

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A total of 211 individuals were screened for entry into the study. Of these, there were 161 participants enrolled in the study and included in the main analyses.

Reporting Groups
  Description
Group A: PEG-IFN Monotherapy Without Advanced Fibrosis Participants without advanced fibrosis were randomized and received peginterferon alfa-2a (PEG-IFN) monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 micrograms (mcg) was based on body surface area (BSA) and given as a once-weekly subcutaneous (SC) injection for 48 weeks. BSA-based dosing was as follows: 0.51–0.53 square meters (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; greater than (>) 1.51 m^2, 180 mcg.
Group B: Untreated Control Without Advanced Fibrosis Participants without advanced fibrosis were randomized and were evaluated for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. As the study is open-label, participants did not receive any investigational or placebo treatment during the 48-week principal observation period (POP). For ethical reasons, participants in Group B had a reduced visit schedule (every 12 weeks) compared to participants in Group A through the end of 24-week follow-up. After completing the POP, the same PEG-IFN regimen administered in Group A was offered to participants in Group B who had not experienced hepatitis B envelope antigen (HBeAg) seroconversion. The offer remained for up to 1 year following the Week 48 visit. From the time a given participant switched to PEG-IFN, he/she was no longer included in Group B.
Group C: PEG-IFN Monotherapy With Advanced Fibrosis Participants with advanced fibrosis were allocated (not randomized) to receive PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was 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.

Participant Flow:   Overall Study
    Group A: PEG-IFN Monotherapy Without Advanced Fibrosis     Group B: Untreated Control Without Advanced Fibrosis     Group C: PEG-IFN Monotherapy With Advanced Fibrosis  
STARTED     101     50     10  
Completed Week 48     99     47     10  
Completed Follow-Up (FU) Week 12     101     26     10  
Completed FU Week 24     101     15     10  
COMPLETED     0     0     0  
NOT COMPLETED     101     50     10  
Ongoing in Follow-Up                 101                 11                 10  
Ongoing/Switched to PEG-IFN                 0                 33                 0  
Adverse Event                 0                 1                 0  
Withdrawal by Subject                 0                 4                 0  
Lost to Follow-up                 0                 1                 0  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full Analysis Population: All participants who were randomized into the study and who were included in any of the study analyses.

Reporting Groups
  Description
Group A: PEG-IFN Monotherapy Without Advanced Fibrosis Participants without advanced fibrosis were randomized and received PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was 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.
Group B: Untreated Control Without Advanced Fibrosis Participants without advanced fibrosis were randomized and were evaluated for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. As the study is open-label, participants did not receive any investigational or placebo treatment during the 48-week POP. For ethical reasons, participants in Group B had a reduced visit schedule (every 12 weeks) compared to participants in Group A through the end of 24-week follow-up. After completing the POP, the same PEG-IFN regimen administered in Group A was offered to participants in Group B who had not experienced HBeAg seroconversion. The offer remained for up to 1 year following the Week 48 visit. From the time a given participant switched to PEG-IFN, he/she was no longer included in Group B.
Group C: PEG-IFN Monotherapy With Advanced Fibrosis Participants with advanced fibrosis were allocated (not randomized) to receive PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was 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.
Total Total of all reporting groups

Baseline Measures
    Group A: PEG-IFN Monotherapy Without Advanced Fibrosis     Group B: Untreated Control Without Advanced Fibrosis     Group C: PEG-IFN Monotherapy With Advanced Fibrosis     Total  
Number of Participants  
[units: participants]
  101     50     10     161  
Age  
[units: years]
Mean (Standard Deviation)
  10.41  (4.57)     11.20  (5.01)     6.70  (3.27)     10.42  (4.73)  
Gender  
[units: participants]
       
Female     37     18     2     57  
Male     64     32     8     104  



  Outcome Measures
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1.  Primary:   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) ]

2.  Secondary:   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) ]

3.  Secondary:   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) ]

4.  Secondary:   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) ]

5.  Secondary:   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) ]

6.  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   [ Time Frame: FU Week 24 (up to 72 weeks overall) ]

7.  Secondary:   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) ]

8.  Secondary:   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) ]

9.  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   [ Time Frame: FU Week 24 (up to 72 weeks overall) ]

10.  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   [ Time Frame: FU Week 24 (up to 72 weeks overall) ]

11.  Secondary:   Percentage of Participants With HBeAg Seroconversion at EOT/POP in Groups A and B   [ Time Frame: Week 48 ]

12.  Secondary:   Percentage of Participants With Loss of HBeAg at EOT/POP in Groups A and B   [ Time Frame: Week 48 ]

13.  Secondary:   Percentage of Participants With HBsAg Seroconversion at EOT/POP in Groups A and B   [ Time Frame: Week 48 ]

14.  Secondary:   Percentage of Participants With Loss of HBsAg at EOT/POP in Groups A and B   [ Time Frame: Week 48 ]

15.  Secondary:   Percentage of Participants With Normal ALT at EOT/POP in Groups A and B   [ Time Frame: Week 48 ]

16.  Secondary:   Percentage of Participants With HBV DNA <20,000 IU/mL at EOT/POP in Groups A and B   [ Time Frame: Week 48 ]

17.  Secondary:   Percentage of Participants With HBV DNA <2,000 IU/mL at EOT/POP in Groups A and B   [ Time Frame: Week 48 ]

18.  Secondary:   Percentage of Participants With HBV DNA Undetectable at EOT/POP in Groups A and B   [ Time Frame: Week 48 ]

19.  Secondary:   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 ]

20.  Secondary:   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 ]

21.  Secondary:   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) ]

22.  Secondary:   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) ]

23.  Secondary:   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) ]

24.  Secondary:   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) ]

25.  Secondary:   Percentage of Participants With HBsAg Seroconversion at 24 Weeks After EOT in Group C   [ Time Frame: FU Week 24 (up to 72 weeks overall) ]

26.  Secondary:   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) ]

27.  Secondary:   Percentage of Participants With Normal ALT at 24 Weeks After EOT in Group C   [ Time Frame: FU Week 24 (up to 72 weeks overall) ]

28.  Secondary:   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) ]

29.  Secondary:   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) ]

30.  Secondary:   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) ]

31.  Secondary:   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) ]

32.  Secondary:   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) ]

33.  Secondary:   Percentage of Participants With HBeAg Seroconversion at EOT in Group C   [ Time Frame: Week 48 ]

34.  Secondary:   Percentage of Participants With Loss of HBeAg at EOT in Group C   [ Time Frame: Week 48 ]

35.  Secondary:   Percentage of Participants With HBsAg Seroconversion at EOT in Group C   [ Time Frame: Week 48 ]

36.  Secondary:   Percentage of Participants With Loss of HBsAg at EOT in Group C   [ Time Frame: Week 48 ]

37.  Secondary:   Percentage of Participants With Normal ALT at EOT in Group C   [ Time Frame: Week 48 ]

38.  Secondary:   Percentage of Participants With HBV DNA <20,000 IU/mL at EOT in Group C   [ Time Frame: Week 48 ]

39.  Secondary:   Percentage of Participants With HBV DNA <2,000 IU/mL at EOT in Group C   [ Time Frame: Week 48 ]

40.  Secondary:   Percentage of Participants With HBV DNA Undetectable at EOT in Group C   [ Time Frame: Week 48 ]

41.  Secondary:   Percentage of Participants With Combined HBeAg Seroconversion and HBV DNA <20,000 IU/mL at EOT in Group C   [ Time Frame: Week 48 ]

42.  Secondary:   Percentage of Participants With Combined HBeAg Seroconversion and HBV DNA <2,000 IU/mL at EOT in Group C   [ Time Frame: Week 48 ]

43.  Secondary:   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) ]

44.  Secondary:   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) ]

45.  Secondary:   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) ]

46.  Secondary:   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) ]

47.  Secondary:   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) ]

48.  Secondary:   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) ]

49.  Secondary:   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) ]

50.  Secondary:   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) ]

51.  Secondary:   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) ]

52.  Secondary:   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) ]

53.  Secondary:   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) ]

54.  Secondary:   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) ]

55.  Secondary:   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) ]

56.  Secondary:   Percentage of Participants With HBeAg Seroconversion at 24 Weeks After EOT in Group C   [ Time Frame: FU Week 24 (up to 72 weeks overall) ]

57.  Secondary:   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) ]

58.  Secondary:   Quantitative HBeAg Level in Groups A and B   [ Time Frame: Baseline; Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall) ]

59.  Secondary:   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) ]

60.  Secondary:   Quantitative HBsAg Level in Groups A and B   [ Time Frame: Baseline; Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall) ]

61.  Secondary:   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) ]

62.  Secondary:   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) ]

63.  Secondary:   Quantitative HBeAg Level in Group C   [ Time Frame: Baseline; Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall) ]

64.  Secondary:   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) ]

65.  Secondary:   Quantitative HBsAg Level in Group C   [ Time Frame: Baseline; Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall) ]

66.  Secondary:   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) ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Results presented above include final analyses of the primary endpoint and most secondary endpoints. Group D had not reached FU Week 24 at time of analysis, so basic safety data were reported. New/updated data will be reported in the final results.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Medical Communications
Organization: Hoffmann-La Roche
phone: 800-821-8590
e-mail: genentech@druginfo.com



Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01519960     History of Changes
Other Study ID Numbers: YV25718
2011-002732-70 ( EudraCT Number )
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