Hepatitis B, Chronic
Conditions
Brief summary
This study will evaluate the efficacy and safety of PEGASYS (peginterferon alfa-2a) in patients with HBeAg positive chronic hepatitis B. Patients will be stratified into group A (treatment naïve patients) or B (YMDD mutant patients). All patients will receive PEGASYS 180 micrograms subcutaneously once weekly for 48 weeks, followed by 24 weeks of treatment-free follow up.
Interventions
DRUGpeginterferon alfa-2a [Pegasys]
Peginterferon alfa-2a (Pegasys) 180 mcg subcutaneously once a week for 48 weeks
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Adult patients, 18-65 years of age * HBsAg +ve for more than 6 months, HBeAg +ve, AntiHBs -ve * Detectable hepatitis B virus (HBV) DNA (\>100,000 copies/mL)
Exclusion criteria
* Coinfection with hepatitis A, hepatitis C or human immunodeficiency virus (HIV) * Evidence of decompensated liver disease * A medical condition associated with chronic liver disease other than viral hepatitis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Hepatitis B Virus DNA <100,000 Copies/mL At Week 72 | Week 72 | 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. |
| Percentage of Participants With Hepatitis B Virus e Antigen Loss At Week 72 | Week 72 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a Combined Response At Week 48 and Week 72 | Week 48 and Week 72 | 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. |
| Percentage of Participants With Hepatitis B Virus e Antigen Seroconversion | Week 48 and Week 72 | A responder was a participant with loss of HBeAg and presence of anti-HBe at EOT and EOF period. |
| Percentage of Participants With ALT Normalization At Week 48 and Week 72 | Week 48 and Week 72 | Participants with ALT less than the upper limit of normal (ULN) at end of treatment (EOT) and EOF period were responders. |
| Percentage of Participants With Hepatitis B Surface Antigen Seroconversion At Week 48 and Week 72 | Week 48 and Week 72 | A responder was a participant with loss of HBsAg and presence of anti-HBs at EOT and EOF period. |
| Number of Participants With Any Adverse Events and Any Serious Adverse Events | Up to Week 72 | 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. |
| Percentage of Participants With Loss of Hepatitis B Surface Antigen At Week 48 and Week 72 | Week 48 and Week 72 | A responder was a participant who were analysed with loss of Hepatitis B Surface Antigen (HBsAg) at EOT and EOF period. |
| Percentage of Participants With Hepatitis B Virus DNA Below the Limit of Detection At Week 48 and Week 72 | Week 48 and Week 72 | Participants with HBV-DNA below the limit of detection i.e. \<174 copies/mL at EOT and EOF period were responders. |
Countries
South Korea
Participant flow
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.
Participants by arm
| Arm | Count |
|---|---|
| PEG-IFN Alfa-2a (Treatment naïve) Eligible treatment naïve participants received PEGASYS 180 mcg SC once weekly for 48 weeks, followed by 24 weeks of treatment-free follow-up. | 86 |
| PEG-IFN Alfa-2a (YMDD Mutant) 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. | 64 |
| Total | 150 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 10 | 9 |
| Overall Study | High alanine aminotransferase (ALT) | 0 | 1 |
| Overall Study | Lack of Efficacy | 4 | 3 |
| Overall Study | Lost to Follow-up | 2 | 1 |
| Overall Study | Treatment refusal | 2 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 0 |
Baseline characteristics
| Characteristic | PEG-IFN Alfa-2a (Treatment naïve) | PEG-IFN Alfa-2a (YMDD Mutant) | Total |
|---|---|---|---|
| Age, Continuous | 35.3 Years STANDARD_DEVIATION 9.2 | 36.8 Years STANDARD_DEVIATION 9 | 35.9 Years STANDARD_DEVIATION 9.1 |
| Sex: Female, Male Female | 23 Participants | 10 Participants | 33 Participants |
| Sex: Female, Male Male | 63 Participants | 54 Participants | 117 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 69 / 86 | 52 / 64 |
| serious Total, serious adverse events | 4 / 86 | 5 / 64 |
Outcome results
Primary
Percentage of Participants With Hepatitis B Virus DNA <100,000 Copies/mL At Week 72
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
Population: Intent-to-treat (ITT) population included all participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PEG-IFN Alfa-2a (Treatment naïve) | Percentage of Participants With Hepatitis B Virus DNA <100,000 Copies/mL At Week 72 | 20.9 percentage of participants |
| PEG-IFN Alfa-2a (YMDD Mutant) | Percentage of Participants With Hepatitis B Virus DNA <100,000 Copies/mL At Week 72 | 21.9 percentage of participants |
Primary
Percentage of Participants With Hepatitis B Virus e Antigen Loss At Week 72
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
Population: The ITT population included all participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PEG-IFN Alfa-2a (Treatment naïve) | Percentage of Participants With Hepatitis B Virus e Antigen Loss At Week 72 | 20.9 Percentage of participants |
| PEG-IFN Alfa-2a (YMDD Mutant) | Percentage of Participants With Hepatitis B Virus e Antigen Loss At Week 72 | 23.4 Percentage of participants |
Secondary
Number of Participants With Any Adverse Events and Any Serious Adverse Events
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
Population: Safety population included participants who received at least one dose of study medication and who had at least one post-baseline safety assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PEG-IFN Alfa-2a (Treatment naïve) | Number of Participants With Any Adverse Events and Any Serious Adverse Events | Any SAEs | 4 Participants |
| PEG-IFN Alfa-2a (Treatment naïve) | Number of Participants With Any Adverse Events and Any Serious Adverse Events | Any AEs | 75 Participants |
| PEG-IFN Alfa-2a (YMDD Mutant) | Number of Participants With Any Adverse Events and Any Serious Adverse Events | Any AEs | 54 Participants |
| PEG-IFN Alfa-2a (YMDD Mutant) | Number of Participants With Any Adverse Events and Any Serious Adverse Events | Any SAEs | 5 Participants |
Secondary
Percentage of Participants With a Combined Response At Week 48 and Week 72
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
Population: The ITT population included all participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PEG-IFN Alfa-2a (Treatment naïve) | Percentage of Participants With a Combined Response At Week 48 and Week 72 | Week 48 (EOT) | 8.1 Percentage of participants |
| PEG-IFN Alfa-2a (Treatment naïve) | Percentage of Participants With a Combined Response At Week 48 and Week 72 | Week 72 (EOF) | 9.3 Percentage of participants |
| PEG-IFN Alfa-2a (YMDD Mutant) | Percentage of Participants With a Combined Response At Week 48 and Week 72 | Week 48 (EOT) | 9.4 Percentage of participants |
| PEG-IFN Alfa-2a (YMDD Mutant) | Percentage of Participants With a Combined Response At Week 48 and Week 72 | Week 72 (EOF) | 14.1 Percentage of participants |
Secondary
Percentage of Participants With ALT Normalization At Week 48 and Week 72
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
Population: The ITT population included all participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PEG-IFN Alfa-2a (Treatment naïve) | Percentage of Participants With ALT Normalization At Week 48 and Week 72 | Week 48 (EOT) | 34.9 percentage of participants |
| PEG-IFN Alfa-2a (Treatment naïve) | Percentage of Participants With ALT Normalization At Week 48 and Week 72 | Week 72 (EOF) | 36.0 percentage of participants |
| PEG-IFN Alfa-2a (YMDD Mutant) | Percentage of Participants With ALT Normalization At Week 48 and Week 72 | Week 48 (EOT) | 29.7 percentage of participants |
| PEG-IFN Alfa-2a (YMDD Mutant) | Percentage of Participants With ALT Normalization At Week 48 and Week 72 | Week 72 (EOF) | 29.7 percentage of participants |
Secondary
Percentage of Participants With Hepatitis B Surface Antigen Seroconversion At Week 48 and Week 72
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
Population: The ITT population included all participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PEG-IFN Alfa-2a (Treatment naïve) | Percentage of Participants With Hepatitis B Surface Antigen Seroconversion At Week 48 and Week 72 | Week 48 (EOT) | 1.2 Percentage of participants |
| PEG-IFN Alfa-2a (Treatment naïve) | Percentage of Participants With Hepatitis B Surface Antigen Seroconversion At Week 48 and Week 72 | Week 72 (EOF) | 1.2 Percentage of participants |
| PEG-IFN Alfa-2a (YMDD Mutant) | Percentage of Participants With Hepatitis B Surface Antigen Seroconversion At Week 48 and Week 72 | Week 48 (EOT) | 0.0 Percentage of participants |
| PEG-IFN Alfa-2a (YMDD Mutant) | Percentage of Participants With Hepatitis B Surface Antigen Seroconversion At Week 48 and Week 72 | Week 72 (EOF) | 1.6 Percentage of participants |
Secondary
Percentage of Participants With Hepatitis B Virus DNA Below the Limit of Detection At Week 48 and Week 72
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
Population: The ITT population included all participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PEG-IFN Alfa-2a (Treatment naïve) | Percentage of Participants With Hepatitis B Virus DNA Below the Limit of Detection At Week 48 and Week 72 | Week 48 (EOT) | 10.5 Percentage of participants |
| PEG-IFN Alfa-2a (Treatment naïve) | Percentage of Participants With Hepatitis B Virus DNA Below the Limit of Detection At Week 48 and Week 72 | Week 72 (EOF) | 3.5 Percentage of participants |
| PEG-IFN Alfa-2a (YMDD Mutant) | Percentage of Participants With Hepatitis B Virus DNA Below the Limit of Detection At Week 48 and Week 72 | Week 48 (EOT) | 10.9 Percentage of participants |
| PEG-IFN Alfa-2a (YMDD Mutant) | Percentage of Participants With Hepatitis B Virus DNA Below the Limit of Detection At Week 48 and Week 72 | Week 72 (EOF) | 9.4 Percentage of participants |
Secondary
Percentage of Participants With Hepatitis B Virus e Antigen Seroconversion
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
Population: The ITT population included all participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PEG-IFN Alfa-2a (Treatment naïve) | Percentage of Participants With Hepatitis B Virus e Antigen Seroconversion | Week 48 (EOT) | 15.1 Percentage of participants |
| PEG-IFN Alfa-2a (Treatment naïve) | Percentage of Participants With Hepatitis B Virus e Antigen Seroconversion | Week 72 (EOF) | 20.9 Percentage of participants |
| PEG-IFN Alfa-2a (YMDD Mutant) | Percentage of Participants With Hepatitis B Virus e Antigen Seroconversion | Week 72 (EOF) | 21.9 Percentage of participants |
| PEG-IFN Alfa-2a (YMDD Mutant) | Percentage of Participants With Hepatitis B Virus e Antigen Seroconversion | Week 48 (EOT) | 23.4 Percentage of participants |
Secondary
Percentage of Participants With Loss of Hepatitis B Surface Antigen At Week 48 and Week 72
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
Population: The ITT population included all participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PEG-IFN Alfa-2a (Treatment naïve) | Percentage of Participants With Loss of Hepatitis B Surface Antigen At Week 48 and Week 72 | Week 48 (EOT) | 1.2 Percentage of participants |
| PEG-IFN Alfa-2a (Treatment naïve) | Percentage of Participants With Loss of Hepatitis B Surface Antigen At Week 48 and Week 72 | Week 72 (EOF) | 1.2 Percentage of participants |
| PEG-IFN Alfa-2a (YMDD Mutant) | Percentage of Participants With Loss of Hepatitis B Surface Antigen At Week 48 and Week 72 | Week 48 (EOT) | 1.6 Percentage of participants |
| PEG-IFN Alfa-2a (YMDD Mutant) | Percentage of Participants With Loss of Hepatitis B Surface Antigen At Week 48 and Week 72 | Week 72 (EOF) | 1.6 Percentage of participants |