Hepatitis B, Chronic
Conditions
Brief summary
This open-label, single-arm, multicenter study will evaluate the efficacy and safety of adding Pegasys (peginterferon alfa-2a) to nucleos(t)ide analogue (NAs) treatment in participants with HBeAg-negative chronic hepatitis B genotype D showing stable HBV DNA suppression. After a 12-week Lead-in period on treatment with NA, participants with a HBsAg decline \<0.5 log10 IU/ml will enter the Add-on period to receive Pegasys 180 mcg subcutaneously weekly for 48 weeks in addition to their current NA treatment. Follow-up will be a further 48 weeks, during which the participants will continue their NA treatment.
Interventions
Peginterferon alfa-2a 180 mcg, subcutaneously (SC) once weekly for 48 weeks.
DRUGNucleos(t)ide Analogues (NA)
Nucleos(t)ide analogues includes adefovir, entecavir, lamivudine or tenofovir.
Sponsors
Hoffmann-La Roche
Study design
Allocation
NA
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 participants, 18 - 65 years of age * Chronic hepatitis B * Negative for HBeAg * On monotherapy with any nucleos(t)ide analogue (NA) but telbivudine at enrolment, and HBV DNA persistently below 20 IU/ml for at least 12 months * HBsAg \>100 IU/ml at the beginning of the Lead-in phase, confirmed before addition of Pegasys * Showing a steady HBsAg kinetic (HBsAg decrease \<0.5 log10 IU/ml from Week -12 to start of the Add-on phase) * Negative pregnancy test for women of childbearing potential * Women of childbearing potential and fertile males with female partners of childbearing potential must be using reliable contraception during and for 3 months after the Add-on phase
Exclusion criteria
* Coinfection with Hepatitis A virus (HAV), Hepatitis C virus (HCV), Hepatitis D virus (HDV), Human Immunodeficiency virus (HIV) * Evidence of decompensated liver disease (Child-Pugh \>/=6) * History or other evidence of a medical condition associated with chronic liver disease (e.g. hemochromatosis, autoimmune hepatitis, alcoholic liver disease, toxin exposure) * Known hypersensitivity to peginterferon alfa-2a * Pregnant of breastfeeding women * Evidence of alcohol and/or drug abuse * History of severe psychiatric disease, especially depression * History of immunologically mediated disease * History or evidence of bleeding from esophageal varices or other conditions consistent with decompensated liver disease * History or evidence of severe pulmonary disease associated with functional limitations * History of severe cardiac disease * History of severe seizure disorder or current anticonvulsant use * Evidence of an active or suspected cancer or a history of malignancy (other than basocellular carcinoma or in situ cervical carcinoma) within 5 years prior to study entry * History of having received any systemic anti-neoplastic (including radiation) or immunomodulatory (including systemic corticosteroids) treatment \</= 6 months prior to the first dose or the expectation that such a treatment will be needed at any time during the study * History or other evidence of severe retinopathy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy: Percent Change From Baseline in Serum Hepatitis B Surface Antigen (HBsAg) Titer at End of the Combination Treatment (Week 48) | Baseline up to Week 48 | — |
| Efficacy: Percentage of Participants With Serum Hepatitis B Surface Antigen (HBsAg) Decrease >/= 50% From Baseline at End of the Combination Treatment (Week 48) | Baseline and Week 48 | Participants who stopped pegylated interferon (PEG-IFN) treatment during the add-on phase due to serum HBsAg loss and HBsAg seroconversion were considered as responders. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy: Number of Participants With Serum HBsAg Loss at Week 12 That Persisted up to Week 96 | Week 12 up to Week 96 | HBsAg loss is defined as HBsAg less than or equal to (\</=) 0.05 IU/ml. |
| Efficacy: HBsAg Levels According to Interleukin 28B (IL28B) Genotypes | Baseline and Week 48 | — |
| Efficacy: Change From Baseline in Serum Hepatitis B Surface Antigen (HBsAg) Titer at Week 24, 72 and 96 | Baseline, Week 24, 72 and 96 | Change is calculated by HBsAg titer at baseline - HBsAg titer at week of assessments. |
| Safety: Percentage of Participants With Adverse Events (AE) | Baseline up to Week 48 | An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. |
| Efficacy: HBsAg Levels According to Interferon-Inducible Protein 10 (IP-10) Serum Levels | Baseline and Week 48 | — |
| Efficacy: Percentage of Participants With HBsAg Decrease >/=1 log10 IU/ml From Baseline to Week 48 | Baseline, Week 48 | — |
Countries
Italy
Participant flow
Pre-assignment details
A total of 76 participants started the study and were included in lead-in period. Out of 76 participants, 70 received study drug.
Participants by arm
| Arm | Count |
|---|---|
| Pegylated Interferon (Peginterferon) Alfa-2a Participants receiving nucleos(t)ide analogues (NA) therapy with Hepatitis B surface Antigen (HBsAg) decline less than \<0.5 log 10 international unit/milliliter (IU/ml) at baseline received peginterferon alfa-2a 180 microgram (mcg), subcutaneously (SC) once weekly for 48 weeks along with their NA therapy. | 76 |
| Total | 76 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 2 |
| Overall Study | Participant Withdrew Consent | 4 |
| Overall Study | Started but not Treated | 6 |
Baseline characteristics
| Characteristic | Pegylated Interferon (Peginterferon) Alfa-2a |
|---|---|
| Age, Continuous | 49.82 years STANDARD_DEVIATION 8.46 |
| Gender Female | 13 Participants |
| Gender Male | 63 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 56 / 69 |
| serious Total, serious adverse events | 5 / 69 |
Outcome results
Primary
Efficacy: Percentage of Participants With Serum Hepatitis B Surface Antigen (HBsAg) Decrease >/= 50% From Baseline at End of the Combination Treatment (Week 48)
Participants who stopped pegylated interferon (PEG-IFN) treatment during the add-on phase due to serum HBsAg loss and HBsAg seroconversion were considered as responders.
Time frame: Baseline and Week 48
Population: PP included all participants without severe protocol violations, including major inclusion or exclusion criteria violations and who were undergoing the Week 48 visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pegylated Interferon (Peginterferon) Alfa-2a | Efficacy: Percentage of Participants With Serum Hepatitis B Surface Antigen (HBsAg) Decrease >/= 50% From Baseline at End of the Combination Treatment (Week 48) | 67.44 percentage of participants |
Primary
Efficacy: Percent Change From Baseline in Serum Hepatitis B Surface Antigen (HBsAg) Titer at End of the Combination Treatment (Week 48)
Time frame: Baseline up to Week 48
Population: Per-Protocol Population (PP) included all participants without severe protocol violations, including major inclusion or exclusion criteria violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pegylated Interferon (Peginterferon) Alfa-2a | Efficacy: Percent Change From Baseline in Serum Hepatitis B Surface Antigen (HBsAg) Titer at End of the Combination Treatment (Week 48) | 59.13 percent change | Standard Deviation 32.14 |
Secondary
Efficacy: Change From Baseline in Serum Hepatitis B Surface Antigen (HBsAg) Titer at Week 24, 72 and 96
Change is calculated by HBsAg titer at baseline - HBsAg titer at week of assessments.
Time frame: Baseline, Week 24, 72 and 96
Population: PP included all participants without severe protocol violations, including major inclusion or exclusion criteria violations. Here, number of participants analyzed signifies those participants who were evaluable for the outcome measure and n signifies the number of participants who were evaluated at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pegylated Interferon (Peginterferon) Alfa-2a | Efficacy: Change From Baseline in Serum Hepatitis B Surface Antigen (HBsAg) Titer at Week 24, 72 and 96 | Baseline (n= 56) | 0 international units per millilitre | Standard Deviation 0 |
| Pegylated Interferon (Peginterferon) Alfa-2a | Efficacy: Change From Baseline in Serum Hepatitis B Surface Antigen (HBsAg) Titer at Week 24, 72 and 96 | Change at Week 24 (n= 56) | -546.32 international units per millilitre | Standard Deviation 1215.2 |
| Pegylated Interferon (Peginterferon) Alfa-2a | Efficacy: Change From Baseline in Serum Hepatitis B Surface Antigen (HBsAg) Titer at Week 24, 72 and 96 | Change at Week 72 (n= 55) | -815.69 international units per millilitre | Standard Deviation 1394.89 |
| Pegylated Interferon (Peginterferon) Alfa-2a | Efficacy: Change From Baseline in Serum Hepatitis B Surface Antigen (HBsAg) Titer at Week 24, 72 and 96 | Change at Week 96 (n= 55) | -728.16 international units per millilitre | Standard Deviation 1418.6 |
Secondary
Efficacy: HBsAg Levels According to Interferon-Inducible Protein 10 (IP-10) Serum Levels
Time frame: Baseline and Week 48
Population: Data were not collected, and the outcome measure was not analyzed.
Secondary
Efficacy: HBsAg Levels According to Interleukin 28B (IL28B) Genotypes
Time frame: Baseline and Week 48
Population: Data were not collected, and the outcome measure was not analyzed.
Secondary
Efficacy: Number of Participants With Serum HBsAg Loss at Week 12 That Persisted up to Week 96
HBsAg loss is defined as HBsAg less than or equal to (\</=) 0.05 IU/ml.
Time frame: Week 12 up to Week 96
Population: PP included all participants without severe protocol violations, including major inclusion or exclusion criteria violations.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pegylated Interferon (Peginterferon) Alfa-2a | Efficacy: Number of Participants With Serum HBsAg Loss at Week 12 That Persisted up to Week 96 | 1 participants |
Secondary
Efficacy: Percentage of Participants With HBsAg Decrease >/=1 log10 IU/ml From Baseline to Week 48
Time frame: Baseline, Week 48
Population: PP included all participants without severe protocol violations, including major inclusion or exclusion criteria violations and who were undergoing the Week 48 visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pegylated Interferon (Peginterferon) Alfa-2a | Efficacy: Percentage of Participants With HBsAg Decrease >/=1 log10 IU/ml From Baseline to Week 48 | 13.95 percentage of participants |
Secondary
Safety: Percentage of Participants With Adverse Events (AE)
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Time frame: Baseline up to Week 48
Population: Safety population included all participants who received least one dose of the study drug and had at least one post-dose safety assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pegylated Interferon (Peginterferon) Alfa-2a | Safety: Percentage of Participants With Adverse Events (AE) | 92.75 percentage of participants |