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

Phase 2

Completed

Interventions: Drug: Pegylated Interferon (Peginterferon) Alfa-2a
Drug: Nucleos(t)ide Analogues (NA)

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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Pegylated Interferon (Peginterferon) Alfa-2a	Nucleos(t)ide Analogues (NA)	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.
Pegylated Interferon (Peginterferon) Alfa-2a	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.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
Efficacy: Percentage of Participants With HBsAg Decrease >/=1 log10 IU/ml From Baseline to Week 48	Baseline, Week 48
Efficacy: HBsAg Levels According to Interferon-Inducible Protein 10 (IP-10) Serum Levels	Baseline and Week 48
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
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.

Locations (13): A.O. Universitaria S. Maria Della Misericordia Di Udine; Oncologia; Clinica Medica
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Udine, Friuli-Venezia Giulia, Italy
Policlinico Umberto I Di Roma
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Roma, Lazio, Italy
Fondazione IRCCS Ospedale Maggiore Policlinico; Gastroenterologia
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Milano, Lombardia, Italy
D.I,M.I.; Cattedra Di Gastroenterologia
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Genova, Liguria, Italy
Nuovo Policlinico; Dipartimento di Malattie Infettive
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Napoli, Campania, Italy
UNI DEGLI STUDI - POLICLINICA S. ORSOLA; Dipartimento Malattie dell'Apparato Digerente e Medicina In
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Bologna, Emilia-Romagna, Italy
A.O. Universitaria S. Giovanni Battista-Molinette Di Torino; Gastroenterologia
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Torino, Piemonte, Italy
A.O. Universitaria Ospedali Riuniti Di Foggia; Malattie Infettive
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Foggia, Puglia, Italy
A.O. Universitaria Policlinico Monserrato Di Cagliari; Gastroenterologia
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Cagliari, Sardegna, Italy
Uni Di Cagliari; Dept. Di Scienze Mediche
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Cagliari, Sardegna, Italy
Az. Osp. Uni. Ria Policlinico G. Martino; Dept. Di Med. Interna E Terapia Medica - Ii Clinica Medica
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Messina, Sicilia, Italy
Istituto Di Clinica Medica 1 A; Divisione Di Medicina Generale E Gastroenterologia
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Palermo, Sicilia, Italy
Ospedale Cisanello - Az. Osp. Pisana; Unità Operativa Di Gastroenterologia Ed Epatologia
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Pisa, Toscana, Italy