Chronic Hepatitis B
Conditions
Keywords
chronic hepatitis B
Brief summary
A prospective, randomised, open-label phase IIb clinical trial assessing the effect of pegylated interferon alfa-2a(Pegasys®) 180 μg once weekly for 48 weeks added to an ongoing nucleos(t)ide based treatment in patients with chronic HBeAg-negative hepatitis B The primary objective of the trial is to investigate whether the add-on of pegylated interferon alfa-2a to a continued treatment with nucleos(t)ide analogues increases the percentage of patients who have significant decrease (≥ 1log10) of HBs antigen after 48 weeks. 170 Patients with chronic hepatitis B, HBe antigen negative, already being treated with an oral antiviral regimen and having a nondetectable viral load for at least 12 months are included.
Interventions
DRUGPegylated interferon alfa-2a plus nucleos(t)ide(s)
Pegylated interferon alfa-2a, s.c. 180 μg 1x/wk in addition to nucleos(t)ide(s)
Sponsors
Roche Pharma AG
Johannes Gutenberg University Mainz
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Chronic hepatitis B, HBe antigen negative * treatment with a stable oral antiviral treatment (not containing telbivudine) and a fully suppressed viral load for at least 12 months (below limit of detection in conventional HBV-PCR assays, i.e. \<116 IU / ml). * 18-70 ys * willingness and ability to give informed consent and to follow study procedures * willingness to use adequate contraception
Exclusion criteria
* contraindications against treatment with pegylated interferon, e.g. depression, uncontrolled epilepsy, autoimmune diseases, pregnancy, leukocytopenia or thrombocytopenia at screening, etc. * active alcohol or drug abuse * preexisting polyneuropathy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference in Percentage of Patients Between Treatment and Comparator Arm Reaching a ≥ 1log10 Decline of Quantitative HBsAg After 48 Weeks | 48 weeks | Difference in percentage of patients between treatment and comparator arm reaching a ≥ 1log10 decline (tenfold reduction) of quantitative HBsAg after 48 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Quantitative HBs Antigen at Week 12 | week 12 | Change in quantitative HBs antigen at week 12. The data were log transformed before analysis and the changes to baseline were analysed. Therefore, the reported values might be interpreted as percentage changes. Lower scores mean a better outcome. |
| Change in Quantitative HBs Antigen at Week 24 | week 24 | Change in quantitative HBs antigen at week 24. The data were log transformed before analysis and the changes to baseline were analysed. Therefore, the reported values might be interpreted as percentage changes. Lower scores mean a better outcome. |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment Group pegylated interferon alfa-2a (Pegasys®) 180 μg once weekly for 48 weeks added to an ongoing nucleos(t)ide based treatment in patients with chronic HBeAg-negative hepatitis B
Pegylated interferon alfa-2a plus nucleos(t)ide(s): Pegylated interferon alfa-2a, s.c. 180 μg 1x/wk in addition to nucleos(t)ide(s) | 110 |
| Control Group ongoing nucleos(t)ide based treatment alone | 55 |
| Total | 165 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 9 | 0 |
| Overall Study | e.g.wish for children, relocation | 6 | 1 |
| Overall Study | Lack of Efficacy | 2 | 0 |
| Overall Study | Lost to Follow-up | 1 | 4 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 4 | 4 |
Baseline characteristics
| Characteristic | Control Group | Total | Treatment Group |
|---|---|---|---|
| Age, Continuous | 45.1 years STANDARD_DEVIATION 9.7 | 44.3 years STANDARD_DEVIATION 9.6 | 43.8 years STANDARD_DEVIATION 9.6 |
| HBsAG Concentration | 8434.9 IU/mL STANDARD_DEVIATION 12660.1 | 7180.6 IU/mL STANDARD_DEVIATION 11159.5 | 6547.5 IU/mL STANDARD_DEVIATION 10326.2 |
| HBV Genotype Genotype A | 1 Participants | 3 Participants | 2 Participants |
| HBV Genotype Genotype C | 0 Participants | 1 Participants | 1 Participants |
| HBV Genotype Genotype D | 11 Participants | 27 Participants | 16 Participants |
| HBV Genotype Genotype E | 0 Participants | 1 Participants | 1 Participants |
| HBV Genotype Not specified | 0 Participants | 1 Participants | 1 Participants |
| HBV Genotype Wildtype | 0 Participants | 1 Participants | 1 Participants |
| HBV Genotype known? No | 43 Participants | 131 Participants | 88 Participants |
| HBV Genotype known? Yes | 12 Participants | 34 Participants | 22 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 21 Participants | 15 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 13 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 7 Participants | 3 Participants |
| Race (NIH/OMB) White | 39 Participants | 124 Participants | 85 Participants |
| Region of Enrollment Germany | 55 participants | 165 participants | 110 participants |
| Sex: Female, Male Female | 16 Participants | 42 Participants | 26 Participants |
| Sex: Female, Male Male | 39 Participants | 123 Participants | 84 Participants |
| Virology: Anti-HBc Negative | 7 Participants | 22 Participants | 15 Participants |
| Virology: Anti-HBc Positive | 48 Participants | 142 Participants | 94 Participants |
| Virology: Anti-HBe Negative | 10 Participants | 21 Participants | 11 Participants |
| Virology: Anti-HBe Positive | 45 Participants | 141 Participants | 96 Participants |
| Virology: Anti-HBs Negative | 53 Participants | 156 Participants | 103 Participants |
| Virology: Anti-HBs Positive | 2 Participants | 9 Participants | 7 Participants |
| Virology: HBeAg Negative | 55 Participants | 165 Participants | 110 Participants |
| Virology: HBeAg Positive | 0 Participants | 0 Participants | 0 Participants |
| Virology: HBV DNA quant. negative? No | 1 Participants | 2 Participants | 1 Participants |
| Virology: HBV DNA quant. negative? Yes | 54 Participants | 163 Participants | 109 Participants |
| Virology: HCV Negative | 55 Participants | 165 Participants | 110 Participants |
| Virology: HCV Positive | 0 Participants | 0 Participants | 0 Participants |
| Virology: HDV Negative | 55 Participants | 165 Participants | 110 Participants |
| Virology: HDV Positive | 0 Participants | 0 Participants | 0 Participants |
| Virology: HIV Negative | 55 Participants | 164 Participants | 109 Participants |
| Virology: HIV Positive | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 112 | 0 / 58 |
| other Total, other adverse events | 106 / 112 | 20 / 58 |
| serious Total, serious adverse events | 13 / 112 | 4 / 58 |
Outcome results
Primary
Difference in Percentage of Patients Between Treatment and Comparator Arm Reaching a ≥ 1log10 Decline of Quantitative HBsAg After 48 Weeks
Difference in percentage of patients between treatment and comparator arm reaching a ≥ 1log10 decline (tenfold reduction) of quantitative HBsAg after 48 weeks
Time frame: 48 weeks
Population: mITT population consisting of all randomized patients with at least one post-baseline measurement
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment Group | Difference in Percentage of Patients Between Treatment and Comparator Arm Reaching a ≥ 1log10 Decline of Quantitative HBsAg After 48 Weeks | Yes | 26 Participants |
| Treatment Group | Difference in Percentage of Patients Between Treatment and Comparator Arm Reaching a ≥ 1log10 Decline of Quantitative HBsAg After 48 Weeks | Missing | 80 Participants |
| Control Group | Difference in Percentage of Patients Between Treatment and Comparator Arm Reaching a ≥ 1log10 Decline of Quantitative HBsAg After 48 Weeks | Yes | 1 Participants |
| Control Group | Difference in Percentage of Patients Between Treatment and Comparator Arm Reaching a ≥ 1log10 Decline of Quantitative HBsAg After 48 Weeks | Missing | 53 Participants |
Comparison: Nullhypothesis was the equality of response rates of the treatment group and the control group. Treatments were compared by a two-sided Fisher test on a level of significance of 0.05. The study was appropriately powered (80%) for this analysis.p-value: <0.0001Fisher Exact
Secondary
Change in Quantitative HBs Antigen at Week 12
Change in quantitative HBs antigen at week 12. The data were log transformed before analysis and the changes to baseline were analysed. Therefore, the reported values might be interpreted as percentage changes. Lower scores mean a better outcome.
Time frame: week 12
Population: Values were only available in 154 patients.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Treatment Group | Change in Quantitative HBs Antigen at Week 12 | 0.7058 IU/ml |
| Control Group | Change in Quantitative HBs Antigen at Week 12 | 0.9380 IU/ml |
p-value: 0.095795% CI: [0.5382, 1.0521]ANCOVA
Secondary
Change in Quantitative HBs Antigen at Week 24
Change in quantitative HBs antigen at week 24. The data were log transformed before analysis and the changes to baseline were analysed. Therefore, the reported values might be interpreted as percentage changes. Lower scores mean a better outcome.
Time frame: week 24
Population: Values were only available in 151 patients.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Treatment Group | Change in Quantitative HBs Antigen at Week 24 | 0.3694 IU/ml |
| Control Group | Change in Quantitative HBs Antigen at Week 24 | 0.7995 IU/ml |
p-value: 0.000595% CI: [0.4621, 0.7106]ANCOVA