A Study of Pegasys (Peginterferon Alfa-2a) Added to Nucleos(t)Ide Analogue Treatment in Participants With HBeAg-Negative Chronic Hepatitis B Genotype D Showing Stable Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Suppression

Study Overview
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Brief Summary
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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.

Official Title
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A Phase IIb, Open Label, Single Arm, Multicenter Study to Evaluate the Effect of 48-weeks PEG-Interferon Alfa-2a (PEG-IFN) Administration on Serum HBsAg in Chronic Hepatitis B, HBeAg-Negative, Genotype D Patients on Treatment With Nucleos(t)Ide Analogues (NAs), Showing Stable HBV DNA Suppression

Conditions
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Hepatitis B, Chronic

Intervention / Treatment
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* Drug: Pegylated Interferon (Peginterferon) Alfa-2a
* Drug: Nucleos(t)ide Analogues (NA)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pegylated Interferon (Peginterferon) Alfa-2a<br>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. | Drug: Pegylated Interferon (Peginterferon) Alfa-2a<br>* Peginterferon alfa-2a 180 mcg, subcutaneously (SC) once weekly for 48 weeks.<br>* Other names: Pegasys;Drug: Nucleos(t)ide Analogues (NA)<br>* Nucleos(t)ide analogues includes adefovir, entecavir, lamivudine or tenofovir.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 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. | Baseline and Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline, Week 24, 72 and 96 | 
| Efficacy: Percentage of Participants With HBsAg Decrease >/=1 log10 IU/ml From Baseline to Week 48 |  | Baseline, Week 48 | 
| 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. | Week 12 up to Week 96 | 
| Efficacy: HBsAg Levels According to Interleukin 28B (IL28B) Genotypes |  | Baseline and Week 48 | 
| Efficacy: HBsAg Levels According to Interferon-Inducible Protein 10 (IP-10) Serum Levels |  | Baseline and Week 48 | 
| 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. | Baseline up to Week 48 |