Clinical trial NCT01706575: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatitis B, Chronic
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2012-10-15
Enrollment: 76
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Efficacy: Percent Change From Baseline in Serum Hepatitis B Surface Antigen (HBsAg) Titer at End of the Combination Treatment (Week 48)
timeFrame: Baseline up to Week 48
measure: Efficacy: Percentage of Participants With Serum Hepatitis B Surface Antigen (HBsAg) Decrease >/= 50% From Baseline at End of the Combination Treatment (Week 48)
timeFrame: Baseline and Week 48
Secondary outcomes:
measure: Efficacy: Change From Baseline in Serum Hepatitis B Surface Antigen (HBsAg) Titer at Week 24, 72 and 96
timeFrame: Baseline, Week 24, 72 and 96
measure: Efficacy: Percentage of Participants With HBsAg Decrease >/=1 log10 IU/ml From Baseline to Week 48
timeFrame: Baseline, Week 48
measure: Efficacy: Number of Participants With Serum HBsAg Loss at Week 12 That Persisted up to Week 96
timeFrame: Week 12 up to Week 96
measure: Efficacy: HBsAg Levels According to Interleukin 28B (IL28B) Genotypes
timeFrame: Baseline and Week 48
measure: Efficacy: HBsAg Levels According to Interferon-Inducible Protein 10 (IP-10) Serum Levels
timeFrame: Baseline and Week 48
measure: Safety: Percentage of Participants With Adverse Events (AE)
timeFrame: Baseline up to Week 48
Other outcomes:
Locations:
city: Napoli
country: Italy
facility: Nuovo Policlinico; Dipartimento di Malattie Infettive
state: Campania
city: Napoli
country: Italy
state: Campania
city: Bologna
country: Italy
facility: UNI DEGLI STUDI - POLICLINICA S. ORSOLA; Dipartimento Malattie dell'Apparato Digerente e Medicina In
state: Emilia-Romagna
city: Bologna
country: Italy
state: Emilia-Romagna
city: Udine
country: Italy
facility: A.O. Universitaria S. Maria Della Misericordia Di Udine; Oncologia; Clinica Medica
state: Friuli-Venezia Giulia
city: Udine
country: Italy
state: Friuli-Venezia Giulia
city: Roma
country: Italy
state: Lazio
city: Roma
country: Italy
facility: Policlinico Umberto I Di Roma
state: Lazio
city: Roma
country: Italy
state: Lazio
city: Genova
country: Italy
facility: D.I,M.I.; Cattedra Di Gastroenterologia
state: Liguria
city: Genova
country: Italy
state: Liguria
city: Milano
country: Italy
facility: Fondazione IRCCS Ospedale Maggiore Policlinico; Gastroenterologia
state: Lombardia
city: Milano
country: Italy
state: Lombardia
city: Torino
country: Italy
facility: A.O. Universitaria S. Giovanni Battista-Molinette Di Torino; Gastroenterologia
state: Piemonte
city: Torino
country: Italy
state: Piemonte
city: Foggia
country: Italy
facility: A.O. Universitaria Ospedali Riuniti Di Foggia; Malattie Infettive
state: Puglia
city: Foggia
country: Italy
state: Puglia
city: Cagliari
country: Italy
facility: A.O. Universitaria Policlinico Monserrato Di Cagliari; Gastroenterologia
state: Sardegna
city: Cagliari
country: Italy
facility: Uni Di Cagliari; Dept. Di Scienze Mediche
state: Sardegna
city: Cagliari
country: Italy
state: Sardegna
city: Messina
country: Italy
facility: Az. Osp. Uni. Ria Policlinico G. Martino; Dept. Di Med. Interna E Terapia Medica - Ii Clinica Medica
state: Sicilia
city: Messina
country: Italy
state: Sicilia
city: Palermo
country: Italy
facility: Istituto Di Clinica Medica 1 A; Divisione Di Medicina Generale E Gastroenterologia
state: Sicilia
city: Palermo
country: Italy
state: Sicilia
city: Pisa
country: Italy
facility: Ospedale Cisanello - Az. Osp. Pisana; Unità Operativa Di Gastroenterologia Ed Epatologia
state: Toscana
city: Pisa
country: Italy
state: Toscana
city: Padova
country: Italy
state: Veneto
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Lampertico P, Brunetto MR, Craxi A, Gaeta GB, Rizzetto M, Rozzi A, Colombo M; HERMES Study Group. Add-on peginterferon alfa-2a to nucleos(t)ide analogue therapy for Caucasian patients with hepatitis B 'e' antigen-negative chronic hepatitis B genotype D. J Viral Hepat. 2019 Jan;26(1):118-125. doi: 10.1111/jvh.12999. Epub 2018 Dec 11.