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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

Primary Purpose

Hepatitis B, Chronic

Status
Completed
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
Pegylated Interferon (Peginterferon) Alfa-2a
Nucleos(t)ide Analogues (NA)
Sponsored by
Hoffmann-La Roche
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatitis B, Chronic

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Nuovo Policlinico; Dipartimento di Malattie Infettive
  • UNI DEGLI STUDI - POLICLINICA S. ORSOLA; Dipartimento Malattie dell'Apparato Digerente e Medicina In
  • A.O. Universitaria S. Maria Della Misericordia Di Udine; Oncologia; Clinica Medica
  • Policlinico Umberto I Di Roma
  • D.I,M.I.; Cattedra Di Gastroenterologia
  • Fondazione IRCCS Ospedale Maggiore Policlinico; Gastroenterologia
  • A.O. Universitaria S. Giovanni Battista-Molinette Di Torino; Gastroenterologia
  • A.O. Universitaria Ospedali Riuniti Di Foggia; Malattie Infettive
  • A.O. Universitaria Policlinico Monserrato Di Cagliari; Gastroenterologia
  • Uni Di Cagliari; Dept. Di Scienze Mediche
  • Az. Osp. Uni. Ria Policlinico G. Martino; Dept. Di Med. Interna E Terapia Medica - Ii Clinica Medica
  • Istituto Di Clinica Medica 1 A; Divisione Di Medicina Generale E Gastroenterologia
  • Ospedale Cisanello - Az. Osp. Pisana; Unità Operativa Di Gastroenterologia Ed Epatologia

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Pegylated Interferon (Peginterferon) Alfa-2a

Arm Description

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.

Outcomes

Primary Outcome Measures

Efficacy: Percent Change From Baseline in Serum Hepatitis B Surface Antigen (HBsAg) Titer at End of the Combination Treatment (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.

Secondary Outcome Measures

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.
Efficacy: Percentage of Participants With HBsAg Decrease >/=1 log10 IU/ml From Baseline to 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.
Efficacy: HBsAg Levels According to Interleukin 28B (IL28B) Genotypes
Efficacy: HBsAg Levels According to Interferon-Inducible Protein 10 (IP-10) Serum Levels
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.

Full Information

First Posted
October 10, 2012
Last Updated
December 29, 2016
Sponsor
Hoffmann-La Roche
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1. Study Identification

Unique Protocol Identification Number
NCT01706575
Brief Title
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

2. Study Status

Record Verification Date
December 2016
Overall Recruitment Status
Completed
Study Start Date
January 2013 (undefined)
Primary Completion Date
September 2013 (Actual)
Study Completion Date
November 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis B, Chronic

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
76 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Pegylated Interferon (Peginterferon) Alfa-2a
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Pegylated Interferon (Peginterferon) Alfa-2a
Other Intervention Name(s)
Pegasys
Intervention Description
Peginterferon alfa-2a 180 mcg, subcutaneously (SC) once weekly for 48 weeks.
Intervention Type
Drug
Intervention Name(s)
Nucleos(t)ide Analogues (NA)
Intervention Description
Nucleos(t)ide analogues includes adefovir, entecavir, lamivudine or tenofovir.
Primary Outcome Measure Information:
Title
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
Title
Efficacy: Percentage of Participants With Serum Hepatitis B Surface Antigen (HBsAg) Decrease >/= 50% From Baseline at End of the Combination Treatment (Week 48)
Description
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
Secondary Outcome Measure Information:
Title
Efficacy: Change From Baseline in Serum Hepatitis B Surface Antigen (HBsAg) Titer at Week 24, 72 and 96
Description
Change is calculated by HBsAg titer at baseline - HBsAg titer at week of assessments.
Time Frame
Baseline, Week 24, 72 and 96
Title
Efficacy: Percentage of Participants With HBsAg Decrease >/=1 log10 IU/ml From Baseline to Week 48
Time Frame
Baseline, Week 48
Title
Efficacy: Number of Participants With Serum HBsAg Loss at Week 12 That Persisted up to Week 96
Description
HBsAg loss is defined as HBsAg less than or equal to (</=) 0.05 IU/ml.
Time Frame
Week 12 up to Week 96
Title
Efficacy: HBsAg Levels According to Interleukin 28B (IL28B) Genotypes
Time Frame
Baseline and Week 48
Title
Efficacy: HBsAg Levels According to Interferon-Inducible Protein 10 (IP-10) Serum Levels
Time Frame
Baseline and Week 48
Title
Safety: Percentage of Participants With Adverse Events (AE)
Description
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
Nuovo Policlinico; Dipartimento di Malattie Infettive
City
Napoli
State/Province
Campania
ZIP/Postal Code
80131
Country
Italy
City
Napoli
State/Province
Campania
ZIP/Postal Code
80131
Country
Italy
Facility Name
UNI DEGLI STUDI - POLICLINICA S. ORSOLA; Dipartimento Malattie dell'Apparato Digerente e Medicina In
City
Bologna
State/Province
Emilia-Romagna
ZIP/Postal Code
40138
Country
Italy
City
Bologna
State/Province
Emilia-Romagna
ZIP/Postal Code
40138
Country
Italy
Facility Name
A.O. Universitaria S. Maria Della Misericordia Di Udine; Oncologia; Clinica Medica
City
Udine
State/Province
Friuli-Venezia Giulia
ZIP/Postal Code
33100
Country
Italy
City
Udine
State/Province
Friuli-Venezia Giulia
ZIP/Postal Code
33100
Country
Italy
City
Roma
State/Province
Lazio
ZIP/Postal Code
00133
Country
Italy
Facility Name
Policlinico Umberto I Di Roma
City
Roma
State/Province
Lazio
ZIP/Postal Code
00161
Country
Italy
City
Roma
State/Province
Lazio
ZIP/Postal Code
00161
Country
Italy
Facility Name
D.I,M.I.; Cattedra Di Gastroenterologia
City
Genova
State/Province
Liguria
ZIP/Postal Code
16132
Country
Italy
City
Genova
State/Province
Liguria
ZIP/Postal Code
16132
Country
Italy
Facility Name
Fondazione IRCCS Ospedale Maggiore Policlinico; Gastroenterologia
City
Milano
State/Province
Lombardia
ZIP/Postal Code
20122
Country
Italy
City
Milano
State/Province
Lombardia
ZIP/Postal Code
20122
Country
Italy
Facility Name
A.O. Universitaria S. Giovanni Battista-Molinette Di Torino; Gastroenterologia
City
Torino
State/Province
Piemonte
ZIP/Postal Code
10126
Country
Italy
City
Torino
State/Province
Piemonte
ZIP/Postal Code
10126
Country
Italy
Facility Name
A.O. Universitaria Ospedali Riuniti Di Foggia; Malattie Infettive
City
Foggia
State/Province
Puglia
ZIP/Postal Code
71100
Country
Italy
City
Foggia
State/Province
Puglia
ZIP/Postal Code
71100
Country
Italy
Facility Name
A.O. Universitaria Policlinico Monserrato Di Cagliari; Gastroenterologia
City
Cagliari
State/Province
Sardegna
ZIP/Postal Code
09042
Country
Italy
Facility Name
Uni Di Cagliari; Dept. Di Scienze Mediche
City
Cagliari
State/Province
Sardegna
ZIP/Postal Code
09042
Country
Italy
City
Cagliari
State/Province
Sardegna
ZIP/Postal Code
09042
Country
Italy
Facility Name
Az. Osp. Uni. Ria Policlinico G. Martino; Dept. Di Med. Interna E Terapia Medica - Ii Clinica Medica
City
Messina
State/Province
Sicilia
ZIP/Postal Code
98124
Country
Italy
City
Messina
State/Province
Sicilia
ZIP/Postal Code
98124
Country
Italy
Facility Name
Istituto Di Clinica Medica 1 A; Divisione Di Medicina Generale E Gastroenterologia
City
Palermo
State/Province
Sicilia
ZIP/Postal Code
90127
Country
Italy
City
Palermo
State/Province
Sicilia
ZIP/Postal Code
90127
Country
Italy
Facility Name
Ospedale Cisanello - Az. Osp. Pisana; Unità Operativa Di Gastroenterologia Ed Epatologia
City
Pisa
State/Province
Toscana
ZIP/Postal Code
56124
Country
Italy
City
Pisa
State/Province
Toscana
ZIP/Postal Code
56124
Country
Italy
City
Padova
State/Province
Veneto
ZIP/Postal Code
35128
Country
Italy

12. IPD Sharing Statement

Citations:
PubMed Identifier
30187599
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.
Results Reference
derived

Learn more about this trial

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

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