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A Study of PEGASYS (Peginterferon Alfa-2a (40KD)) in Patients With HBeAg Positive Chronic Hepatitis B.

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ClinicalTrials.gov Identifier: NCT01519921
Recruitment Status : Completed
First Posted : January 27, 2012
Results First Posted : January 25, 2016
Last Update Posted : April 21, 2016
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Hepatitis B, Chronic
Intervention Drug: peginterferon alfa-2a [Pegasys]
Enrollment 150
Recruitment Details A total of 150 participants were enrolled in this study conducted from 26 October 2005 to 24 June 2008 at 7 centers in Republic of Korea.
Pre-assignment Details  
Arm/Group Title PEG-IFN Alfa-2a (Treatment naïve) PEG-IFN Alfa-2a (YMDD Mutant)
Hide Arm/Group Description Eligible treatment naïve participants received peginterferon alfa-2a (PEGASYS) 180 micrograms (mcg) subcutaneously (SC) once weekly for 48 weeks, followed by 24 weeks of treatment-free follow-up. Eligible tyrosine-methionine-aspartate-aspartate (YMDD) mutant participants received PEGASYS 180mcg SC once weekly for 48 weeks, followed by 24 weeks of treatment-free follow- up. Participants received lamivudine concomitantly for the initial 12 weeks.
Period Title: Overall Study
Started 86 64
Completed 65 49
Not Completed 21 15
Reason Not Completed
Adverse Event             10             9
Lack of Efficacy             4             3
Withdrawal by Subject             3             0
Lost to Follow-up             2             1
Treatment refusal             2             1
High alanine aminotransferase (ALT)             0             1
Arm/Group Title PEG-IFN Alfa-2a (Treatment naïve) PEG-IFN Alfa-2a (YMDD Mutant) Total
Hide Arm/Group Description Eligible treatment naïve participants received PEGASYS 180 mcg SC once weekly for 48 weeks, followed by 24 weeks of treatment-free follow-up. Eligible YMDD mutant participants received PEGASYS 180 mcg SC once weekly for 48 weeks, followed by 24 weeks of treatment-free follow- up. Participants received lamivudine concomitantly for the initial 12 weeks. Total of all reporting groups
Overall Number of Baseline Participants 86 64 150
Hide Baseline Analysis Population Description
Baseline characteristics were analysed on Intent-to-treat (ITT) population which included all participants who received at least one dose of study drug. The ITT and the safety populations were identical.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 86 participants 64 participants 150 participants
35.3  (9.20) 36.8  (9.0) 35.9  (9.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 86 participants 64 participants 150 participants
Female
23
  26.7%
10
  15.6%
33
  22.0%
Male
63
  73.3%
54
  84.4%
117
  78.0%
1.Primary Outcome
Title Percentage of Participants With Hepatitis B Virus DNA <100,000 Copies/mL At Week 72
Hide Description Participants who had Hepatitis B Virus Deoxyribonucleic Acid (HBV-DNA) levels below 100,000 copies per milliliter (mL) at the end of follow-up (EOF) period (24 weeks after the end of treatment) were classified as responders.
Time Frame Week 72
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population included all participants who received at least one dose of study drug.
Arm/Group Title PEG-IFN Alfa-2a (Treatment naïve) PEG-IFN Alfa-2a (YMDD Mutant)
Hide Arm/Group Description:
Eligible treatment naïve participants received PEGASYS 180 mcg SC once weekly for 48 weeks, followed by 24 weeks of treatment-free follow-up.
Eligible YMDD mutant participants received PEGASYS 180 mcg SC once weekly for 48 weeks, followed by 24 weeks of treatment-free follow- up. Participants received lamivudine concomitantly for the initial 12 weeks.
Overall Number of Participants Analyzed 86 64
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
20.9
(12.9 to 31.0)
21.9
(12.5 to 34.0)
2.Primary Outcome
Title Percentage of Participants With Hepatitis B Virus e Antigen Loss At Week 72
Hide Description Participants with loss of hepatitis B virus e antigen (HBeAg) at the EOF period (24 weeks after the end of treatment) were classified as responders.
Time Frame Week 72
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all participants who received at least one dose of study drug.
Arm/Group Title PEG-IFN Alfa-2a (Treatment naïve) PEG-IFN Alfa-2a (YMDD Mutant)
Hide Arm/Group Description:
Eligible treatment naïve participants received PEGASYS 180 mcg SC once weekly for 48 weeks, followed by 24 weeks of treatment-free follow-up.
Eligible YMDD mutant participants received PEGASYS 180 mcg SC once weekly for 48 weeks, followed by 24 weeks of treatment-free follow- up. Participants received lamivudine concomitantly for the initial 12 weeks.
Overall Number of Participants Analyzed 86 64
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
20.9
(12.9 to 31.0)
23.4
(13.8 to 35.7)
3.Secondary Outcome
Title Percentage of Participants With ALT Normalization At Week 48 and Week 72
Hide Description Participants with ALT less than the upper limit of normal (ULN) at end of treatment (EOT) and EOF period were responders.
Time Frame Week 48 and Week 72
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all participants who received at least one dose of study drug.
Arm/Group Title PEG-IFN Alfa-2a (Treatment naïve) PEG-IFN Alfa-2a (YMDD Mutant)
Hide Arm/Group Description:
Eligible treatment naïve participants received PEGASYS 180 mcg SC once weekly for 48 weeks, followed by 24 weeks of treatment-free follow-up.
Eligible YMDD mutant participants received PEGASYS 180 mcg SC once weekly for 48 weeks, followed by 24 weeks of treatment-free follow- up. Participants received lamivudine concomitantly for the initial 12 weeks.
Overall Number of Participants Analyzed 86 64
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Week 48 (EOT)
34.9
(24.9 to 45.9)
29.7
(18.9 to 42.4)
Week 72 (EOF)
36.0
(26.0 to 47.1)
29.7
(18.9 to 42.4)
4.Secondary Outcome
Title Percentage of Participants With Hepatitis B Virus DNA Below the Limit of Detection At Week 48 and Week 72
Hide Description Participants with HBV-DNA below the limit of detection i.e. <174 copies/mL at EOT and EOF period were responders.
Time Frame Week 48 and Week 72
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all participants who received at least one dose of study drug.
Arm/Group Title PEG-IFN Alfa-2a (Treatment naïve) PEG-IFN Alfa-2a (YMDD Mutant)
Hide Arm/Group Description:
Eligible treatment naïve participants received PEGASYS 180 mcg SC once weekly for 48 weeks, followed by 24 weeks of treatment-free follow-up.
Eligible YMDD mutant participants received PEGASYS 180 mcg SC once weekly for 48 weeks, followed by 24 weeks of treatment-free follow- up. Participants received lamivudine concomitantly for the initial 12 weeks.
Overall Number of Participants Analyzed 86 64
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
Week 48 (EOT)
10.5
(4.9 to 18.9)
10.9
(4.5 to 21.2)
Week 72 (EOF)
3.5
(0.7 to 9.9)
9.4
(3.5 to 19.3)
5.Secondary Outcome
Title Percentage of Participants With a Combined Response At Week 48 and Week 72
Hide Description A responder with Combined Response was a participant with HBV-DNA<100,000 copies/mL, HBeAg seroconversion (i.e. loss of HBeAg and presence of anti-HBe) and ALT normalization at EOT and EOF period.
Time Frame Week 48 and Week 72
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all participants who received at least one dose of study drug.
Arm/Group Title PEG-IFN Alfa-2a (Treatment naïve) PEG-IFN Alfa-2a (YMDD Mutant)
Hide Arm/Group Description:
Eligible treatment naïve participants received PEGASYS 180 mcg SC once weekly for 48 weeks, followed by 24 weeks of treatment-free follow-up.
Eligible YMDD mutant participants received PEGASYS 180 mcg SC once weekly for 48 weeks, followed by 24 weeks of treatment-free follow- up. Participants received lamivudine concomitantly for the initial 12 weeks.
Overall Number of Participants Analyzed 86 64
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
Week 48 (EOT)
8.1
(3.3 to 16.1)
9.4
(3.5 to 19.3)
Week 72 (EOF)
9.3
(4.1 to 17.5)
14.1
(6.6 to 25.0)
6.Secondary Outcome
Title Percentage of Participants With Hepatitis B Virus e Antigen Seroconversion
Hide Description A responder was a participant with loss of HBeAg and presence of anti-HBe at EOT and EOF period.
Time Frame Week 48 and Week 72
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all participants who received at least one dose of study drug.
Arm/Group Title PEG-IFN Alfa-2a (Treatment naïve) PEG-IFN Alfa-2a (YMDD Mutant)
Hide Arm/Group Description:
Eligible treatment naïve participants received PEGASYS 180 mcg SC once weekly for 48 weeks, followed by 24 weeks of treatment-free follow-up.
Eligible YMDD mutant participants received PEGASYS 180 mcg SC once weekly for 48 weeks, followed by 24 weeks of treatment-free follow- up. Participants received lamivudine concomitantly for the initial 12 weeks.
Overall Number of Participants Analyzed 86 64
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
Week 48 (EOT)
15.1
(8.3 to 24.5)
23.4
(13.8 to 35.7)
Week 72 (EOF)
20.9
(12.9 to 31.0)
21.9
(12.5 to 34.0)
7.Secondary Outcome
Title Percentage of Participants With Loss of Hepatitis B Surface Antigen At Week 48 and Week 72
Hide Description A responder was a participant who were analysed with loss of Hepatitis B Surface Antigen (HBsAg) at EOT and EOF period.
Time Frame Week 48 and Week 72
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all participants who received at least one dose of study drug.
Arm/Group Title PEG-IFN Alfa-2a (Treatment naïve) PEG-IFN Alfa-2a (YMDD Mutant)
Hide Arm/Group Description:
Eligible treatment naïve participants received PEGASYS 180 mcg SC once weekly for 48 weeks, followed by 24 weeks of treatment-free follow-up.
Eligible YMDD mutant participants received PEGASYS 180 mcg SC once weekly for 48 weeks, followed by 24 weeks of treatment-free follow- up. Participants received lamivudine concomitantly for the initial 12 weeks.
Overall Number of Participants Analyzed 86 64
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
Week 48 (EOT)
1.2
(0.03 to 6.3)
1.6
(0.04 to 8.4)
Week 72 (EOF)
1.2
(0.03 to 6.3)
1.6
(0.04 to 8.4)
8.Secondary Outcome
Title Percentage of Participants With Hepatitis B Surface Antigen Seroconversion At Week 48 and Week 72
Hide Description A responder was a participant with loss of HBsAg and presence of anti-HBs at EOT and EOF period.
Time Frame Week 48 and Week 72
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all participants who received at least one dose of study drug.
Arm/Group Title PEG-IFN Alfa-2a (Treatment naïve) PEG-IFN Alfa-2a (YMDD Mutant)
Hide Arm/Group Description:
Eligible treatment naïve participants received PEGASYS 180 mcg SC once weekly for 48 weeks, followed by 24 weeks of treatment-free follow-up.
Eligible YMDD mutant participants received PEGASYS 180 mcg SC once weekly for 48 weeks, followed by 24 weeks of treatment-free follow- up. Participants received lamivudine concomitantly for the initial 12 weeks.
Overall Number of Participants Analyzed 86 64
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
Week 48 (EOT)
1.2
(0.03 to 6.3)
0.0
(0.0 to 0.0)
Week 72 (EOF)
1.2
(0.03 to 6.3)
1.6
(0.04 to 8.4)
9.Secondary Outcome
Title Number of Participants With Any Adverse Events and Any Serious Adverse Events
Hide Description An adverse event (AE) was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started. An adverse event was therefore any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A Serious Adverse Events (SAE) is any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, and congenital anomaly/birth defect. Participants with any AEs and any SAEs have been presented.
Time Frame Up to Week 72
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included participants who received at least one dose of study medication and who had at least one post-baseline safety assessment.
Arm/Group Title PEG-IFN Alfa-2a (Treatment naïve) PEG-IFN Alfa-2a (YMDD Mutant)
Hide Arm/Group Description:
Eligible treatment naïve participants received PEGASYS 180 mcg SC once weekly for 48 weeks, followed by 24 weeks of treatment-free follow-up.
Eligible YMDD mutant participants received PEGASYS 180 mcg SC once weekly for 48 weeks, followed by 24 weeks of treatment-free follow- up. Participants received lamivudine concomitantly for the initial 12 weeks.
Overall Number of Participants Analyzed 86 64
Measure Type: Number
Unit of Measure: Participants
Any AEs 75 54
Any SAEs 4 5
Time Frame Up to Week 72
Adverse Event Reporting Description An AE was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started. An AE was therefore any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug.
 
Arm/Group Title PEG-IFN Alfa-2a (Treatment naïve) PEG-IFN Alfa-2a (YMDD Mutant)
Hide Arm/Group Description Eligible treatment naïve participants received PEGASYS 180 mcg SC once weekly for 48 weeks, followed by 24 weeks of treatment-free follow-up. Group B included tyrosine-methionine-aspartate-aspartate (YMDD) mutant participants who received PEGASYS 180mcg subcutaneously once weekly for 48 weeks, followed by 24 weeks of treatment-free follow- up.
All-Cause Mortality
PEG-IFN Alfa-2a (Treatment naïve) PEG-IFN Alfa-2a (YMDD Mutant)
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
PEG-IFN Alfa-2a (Treatment naïve) PEG-IFN Alfa-2a (YMDD Mutant)
Affected / at Risk (%) Affected / at Risk (%)
Total   4/86 (4.65%)   5/64 (7.81%) 
Blood and lymphatic system disorders     
Lymphadenopathy  1  1/86 (1.16%)  0/64 (0.00%) 
Gastrointestinal disorders     
Abdominal pain upper  1  0/86 (0.00%)  1/64 (1.56%) 
Appendicitis  1  0/86 (0.00%)  1/64 (1.56%) 
Exomphalos  1  1/86 (1.16%)  0/64 (0.00%) 
Haemorrhoids  1  1/86 (1.16%)  0/64 (0.00%) 
General disorders     
Pyrexia  1  1/86 (1.16%)  1/64 (1.56%) 
Hepatobiliary disorders     
Cholecystitis acute  1  0/86 (0.00%)  1/64 (1.56%) 
Injury, poisoning and procedural complications     
Wrist fracture  1  0/86 (0.00%)  1/64 (1.56%) 
Investigations     
Liver function test abnormal  1  0/86 (0.00%)  2/64 (3.13%) 
Respiratory, thoracic and mediastinal disorders     
Bronchopneumonia  1  1/86 (1.16%)  0/64 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 11.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
PEG-IFN Alfa-2a (Treatment naïve) PEG-IFN Alfa-2a (YMDD Mutant)
Affected / at Risk (%) Affected / at Risk (%)
Total   69/86 (80.23%)   52/64 (81.25%) 
Blood and lymphatic system disorders     
Neutropenia  1  21/86 (24.42%)  18/64 (28.13%) 
Gastrointestinal disorders     
Abdominal pain upper  1  2/86 (2.33%)  4/64 (6.25%) 
Diarrhoea  1  7/86 (8.14%)  5/64 (7.81%) 
Dyspepsia  1  10/86 (11.63%)  1/64 (1.56%) 
Nausea  1  3/86 (3.49%)  4/64 (6.25%) 
General disorders     
Asthenia  1  7/86 (8.14%)  5/64 (7.81%) 
Fatigue  1  16/86 (18.60%)  17/64 (26.56%) 
Influenza like illness  1  11/86 (12.79%)  12/64 (18.75%) 
Pain  1  13/86 (15.12%)  6/64 (9.38%) 
Pyrexia  1  3/86 (3.49%)  6/64 (9.38%) 
Investigations     
Liver function test abnormal  1  10/86 (11.63%)  7/64 (10.94%) 
Weight decreased  1  5/86 (5.81%)  1/64 (1.56%) 
Metabolism and nutrition disorders     
Anorexia  1  2/86 (2.33%)  4/64 (6.25%) 
Musculoskeletal and connective tissue disorders     
Myalgia  1  9/86 (10.47%)  6/64 (9.38%) 
Nervous system disorders     
Dizziness  1  6/86 (6.98%)  2/64 (3.13%) 
Headache  1  16/86 (18.60%)  15/64 (23.44%) 
Psychiatric disorders     
Insomnia  1  4/86 (4.65%)  4/64 (6.25%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  5/86 (5.81%)  2/64 (3.13%) 
Pharyngolaryngeal pain  1  6/86 (6.98%)  2/64 (3.13%) 
Upper respiratory tract infection  1  10/86 (11.63%)  13/64 (20.31%) 
Skin and subcutaneous tissue disorders     
Alopecia  1  34/86 (39.53%)  24/64 (37.50%) 
Pruritus  1  11/86 (12.79%)  12/64 (18.75%) 
Urticaria  1  4/86 (4.65%)  4/64 (6.25%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 11.0
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 Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
Name/Title: Roche Trial Information Hotline
Organization: F. Hoffmann-La Roche AG
Phone: +41 616878333
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01519921     History of Changes
Other Study ID Numbers: ML18495
First Submitted: January 5, 2012
First Posted: January 27, 2012
Results First Submitted: December 17, 2015
Results First Posted: January 25, 2016
Last Update Posted: April 21, 2016