Back to resultsA Study of Pegylated Interferon Alfa-2a and Lamivudine in Patients With HBeAg-Negative Chronic Hepatitis B Virus (HBV)
Primary Purpose
Hepatitis B, Chronic
Status
Completed
Phase
Phase 3
Locations
Italy
Study Type
Interventional
Intervention
Pegylated interferon (PEG-IFN) alfa-2a, 180 mcg
Pegylated interferon (PEG-IFN) alfa-2a, 135 mcg
Lamivudine (LAM)
Sponsored by
About this trial
This is an interventional treatment trial for Hepatitis B, Chronic
Eligibility Criteria
Inclusion Criteria:
- adults 18-70 years of age;
- HBeAg-negative chronic hepatitis B for >/=6 months;
- liver disease consistent with chronic hepatitis B.
Exclusion Criteria:
- interferon-based, systemic anti-HBV, antiviral, anti-neoplastic, or immunomodulatory therapy </=12 months before first dose of study drug;
- non-responders to previous interferon therapy;
- co-infection with hepatitis A, C or D, or with human immunodeficiency virus (HIV);
- hepatocellular cancer;
- compensated (Child A, score 6) or decompensated liver disease (Child B or C).
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
PEG-IFN48
PEG-IFN96
PEG-IFN+LAM96
Arm Description
Treatment with PEG-IFN in participants with HBeAg-negative chronic hepatitis B virus for 48 weeks.
Treatment with PEG-IFN in participants with HBeAg-negative chronic hepatitis B virus for 48 weeks followed by another 48 weeks of PEG-IFN treatment (total 96 weeks of treatment).
Treatment with PEG-IFN and lamivudine in participants with HBeAg-negative chronic hepatitis B virus for 48 weeks followed by 48 weeks of only PEG-IFN treatment (total 96 weeks of treatment).
Outcomes
Primary Outcome Measures
Percentage of Participants Achieving the Combined Response at the End of the Follow-up Period
Combined response was defined as alanine aminotransferase (ALT) normalization plus lowering of hepatitis B virus (HBV) deoxyribo nucleic acid (DNA) levels to <20,000 copies/mL (<3,400 IU/mL) and was measured at the end of the 48-week follow-up period. Participants with missing 48 weeks follow-up measurements were considered as non-responders. However, if the scheduled 48-weeks post-treatment tests were performed earlier or later than 48 weeks post-treatment, but not earlier than 36 weeks post-treatment, the corresponding results were considered to determine response.
Secondary Outcome Measures
Percentage of Participants Achieving the Combined Response at the End of Treatment
Combined response was defined as ALT normalization plus lowering of HBV-DNA levels to <20,000 copies/mL (<3,400 IU/mL). In case of missing end of treatment measurements, the next available post-treatment value was used.
Percentage of Participants Achieving the Combined Response at 24 Weeks of Follow-up
Combined response was defined as ALT normalization plus lowering of HBV-DNA levels to <20,000 copies/mL (<3,400 IU/mL). In case of missing week-24 post-treatment measurements, the nearest value with respect to the schedule time point in the time window 12 weeks post treatment until study end was used.
Percentage of Participants Achieving Combined Response Using a Cut-Off for HBV-DNA Levels to 2,000 IU/mL
Combined response was defined here as ALT normalization plus lowering HBV-DNA levels to a cutt-off <2,000 IU/mL. In case of missing end of treatment measurements, the next available post-treatment value was used. In case of missing week-24 post-treatment measurements, the nearest value with respect to the schedule time point in the time window 12 weeks post treatment until study end was used. Participants with missing 48 weeks follow-up measurements were considered as non-responders. However, if the scheduled 48-weeks post-treatment tests were performed earlier or later than 48 weeks post-treatment, but not earlier than 36 weeks post-treatment, the corresponding results were considered to determine response.
Percentage of Participants Achieving Histological Response
Histological response was defined as an improvement by >/= 2 in the Necroinflammatory Grading and/or by an improvement by >/= 1 score in Fibrosis Staging according to Ishak. Necroinflammatory Grading ranges 0-14 and is the combined score for necrosis, range 0-10 and inflammation, range 0-4. The participant is scored for only one inflammatory condition. A higher score indicates worse condition. Fibrosis Staging according to Ishak ranges 0-6 and a higher score indicates greater fibrosis.
Change From Baseline of Quantitative Hepatitis B Surface Antigen (HbsAg) Level at the End of Treatment
Percentage of Participants With Lamivudine Genotype Resistance During PEG-IFN+LAM96 Combined Therapy
Lamivudine resistance mutations were assessed by detection of the following mutations: rtL80V, rtL80I, rtV173G, rtV173L, rtL180M, rtA181T, rtA181V, rtM204V, rtM204I and rtN236T.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01095835
Brief Title
A Study of Pegylated Interferon Alfa-2a and Lamivudine in Patients With HBeAg-Negative Chronic Hepatitis B Virus (HBV)
Official Title
A Multicenter, Randomized, Controlled Study Comparing the Efficacy and Safety of 48 Weeks of 40kD Branched Pegylated Interferon Alfa-2a (PEG-IFN, RO 25-8310) Versus 96 Weeks of PEG-IFN, Alone or in Combination With 100 mg Lamivudine for 48 Weeks in Patients With HBeAg-Negative Chronic Hepatitis B
Study Type
Interventional
2. Study Status
Record Verification Date
March 2016
Overall Recruitment Status
Completed
Study Start Date
February 2005 (undefined)
Primary Completion Date
January 2010 (Actual)
Study Completion Date
January 2010 (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 study will compare the efficacy and safety of 2 different durations of treatment with pegylated interferon (PEG-IFN) alfa-2a in participants with Hepatitis B e Antigen (HBeAg)-negative chronic hepatitis B virus (HBV). It will also compare PEG-IFN alfa 2a treatment alone and in combination with lamivudine (LAM). The anticipated time on study treatment is 1-2 years, and the target sample size is 100-500 individuals.
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 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
131 (Actual)
8. Arms, Groups, and Interventions
Arm Title
PEG-IFN48
Arm Type
Experimental
Arm Description
Treatment with PEG-IFN in participants with HBeAg-negative chronic hepatitis B virus for 48 weeks.
Arm Title
PEG-IFN96
Arm Type
Experimental
Arm Description
Treatment with PEG-IFN in participants with HBeAg-negative chronic hepatitis B virus for 48 weeks followed by another 48 weeks of PEG-IFN treatment (total 96 weeks of treatment).
Arm Title
PEG-IFN+LAM96
Arm Type
Experimental
Arm Description
Treatment with PEG-IFN and lamivudine in participants with HBeAg-negative chronic hepatitis B virus for 48 weeks followed by 48 weeks of only PEG-IFN treatment (total 96 weeks of treatment).
Intervention Type
Drug
Intervention Name(s)
Pegylated interferon (PEG-IFN) alfa-2a, 180 mcg
Other Intervention Name(s)
Pegasys®
Intervention Description
PEG-IFN alfa-2a 180 micrograms (mcg) was administered subcutaneously, once weekly from Week 0 to 48.
Intervention Type
Drug
Intervention Name(s)
Pegylated interferon (PEG-IFN) alfa-2a, 135 mcg
Other Intervention Name(s)
Pegasys®
Intervention Description
PEG-IFN alfa-2a 135 mcg was administered subcutaneously, once weekly from Week 49 to 96.
Intervention Type
Drug
Intervention Name(s)
Lamivudine (LAM)
Intervention Description
Lamivudine 100 milligrams (mg) was administered orally, daily from Week 0 to 48.
Primary Outcome Measure Information:
Title
Percentage of Participants Achieving the Combined Response at the End of the Follow-up Period
Description
Combined response was defined as alanine aminotransferase (ALT) normalization plus lowering of hepatitis B virus (HBV) deoxyribo nucleic acid (DNA) levels to <20,000 copies/mL (<3,400 IU/mL) and was measured at the end of the 48-week follow-up period. Participants with missing 48 weeks follow-up measurements were considered as non-responders. However, if the scheduled 48-weeks post-treatment tests were performed earlier or later than 48 weeks post-treatment, but not earlier than 36 weeks post-treatment, the corresponding results were considered to determine response.
Time Frame
At the end of the 48-week follow-up period at Week 144
Secondary Outcome Measure Information:
Title
Percentage of Participants Achieving the Combined Response at the End of Treatment
Description
Combined response was defined as ALT normalization plus lowering of HBV-DNA levels to <20,000 copies/mL (<3,400 IU/mL). In case of missing end of treatment measurements, the next available post-treatment value was used.
Time Frame
At end of treatment at Week 48 or 96 depending on the study arm
Title
Percentage of Participants Achieving the Combined Response at 24 Weeks of Follow-up
Description
Combined response was defined as ALT normalization plus lowering of HBV-DNA levels to <20,000 copies/mL (<3,400 IU/mL). In case of missing week-24 post-treatment measurements, the nearest value with respect to the schedule time point in the time window 12 weeks post treatment until study end was used.
Time Frame
At the end of 24 weeks of follow-up at Week 120
Title
Percentage of Participants Achieving Combined Response Using a Cut-Off for HBV-DNA Levels to 2,000 IU/mL
Description
Combined response was defined here as ALT normalization plus lowering HBV-DNA levels to a cutt-off <2,000 IU/mL. In case of missing end of treatment measurements, the next available post-treatment value was used. In case of missing week-24 post-treatment measurements, the nearest value with respect to the schedule time point in the time window 12 weeks post treatment until study end was used. Participants with missing 48 weeks follow-up measurements were considered as non-responders. However, if the scheduled 48-weeks post-treatment tests were performed earlier or later than 48 weeks post-treatment, but not earlier than 36 weeks post-treatment, the corresponding results were considered to determine response.
Time Frame
At end of treatment at Week 48 or 96 depending on the study arm, at the end of 24 weeks of follow-up at Week 120 and at the end of the follow-up period at Week 144
Title
Percentage of Participants Achieving Histological Response
Description
Histological response was defined as an improvement by >/= 2 in the Necroinflammatory Grading and/or by an improvement by >/= 1 score in Fibrosis Staging according to Ishak. Necroinflammatory Grading ranges 0-14 and is the combined score for necrosis, range 0-10 and inflammation, range 0-4. The participant is scored for only one inflammatory condition. A higher score indicates worse condition. Fibrosis Staging according to Ishak ranges 0-6 and a higher score indicates greater fibrosis.
Time Frame
At the end of the 48-week follow-up period at Week 144
Title
Change From Baseline of Quantitative Hepatitis B Surface Antigen (HbsAg) Level at the End of Treatment
Time Frame
At the end of treatment at Week 48 or 96 depending on the study arm
Title
Percentage of Participants With Lamivudine Genotype Resistance During PEG-IFN+LAM96 Combined Therapy
Description
Lamivudine resistance mutations were assessed by detection of the following mutations: rtL80V, rtL80I, rtV173G, rtV173L, rtL180M, rtA181T, rtA181V, rtM204V, rtM204I and rtN236T.
Time Frame
At the end of the treatment period at Week 96
Other Pre-specified Outcome Measures:
Title
Percentage of Participants With ALT Normalization
Time Frame
At end of treatment at Week 48 or 96 depending on the study arm, at the end of 24 weeks of follow-up at Week 120 and at the end of the follow-up period at Week 144
Title
Percentage of Participants With HBV-DNA Lowering to <3,400 IU/mL and to < 2,000 IU/mL
Time Frame
At end of treatment at Week 48 or 96 depending on the study arm, at the end of 24 weeks of follow-up at Week 120 and at the end of the follow-up period at Week 144
Title
Percentage of Participants With HBV-DNA Below Limit of Quantification
Description
HBV-DNA limit < 6 IU/mL was defined as below quantification.
Time Frame
At end of treatment at Week 48 or 96 depending on the study arm, at the end of 24 weeks of follow-up at Week 120 and at the end of the follow-up period at Week 144
Title
Percentage of Participants With Loss of Hepatitis B Surface Antigen (HbsAg) and Hepatitis B Surface Antibodies (Anti-HBs) Seroconversion
Description
This outcome measure presents percentage of participants with a combined response of HBsAg < 5 IU/mL and anti-HBs positive. Positive anti-HBs represents antibodies produced against Hepatitis B Surface Antigen (HBsAg) and is an indication of recovery and immunity from HBV infection.
Time Frame
At end of treatment at Week 48 or 96 depending on the study arm, at the end of 24 weeks of follow-up at Week 120 and at the end of the follow-up period at Week 144
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
adults 18-70 years of age;
HBeAg-negative chronic hepatitis B for >/=6 months;
liver disease consistent with chronic hepatitis B.
Exclusion Criteria:
interferon-based, systemic anti-HBV, antiviral, anti-neoplastic, or immunomodulatory therapy </=12 months before first dose of study drug;
non-responders to previous interferon therapy;
co-infection with hepatitis A, C or D, or with human immunodeficiency virus (HIV);
hepatocellular cancer;
compensated (Child A, score 6) or decompensated liver disease (Child B or C).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
City
Caserta
State/Province
Campania
ZIP/Postal Code
81100
Country
Italy
City
Napoli
State/Province
Campania
ZIP/Postal Code
80131
Country
Italy
City
Napoli
State/Province
Campania
ZIP/Postal Code
80135
Country
Italy
City
Bologna
State/Province
Emilia-Romagna
ZIP/Postal Code
40138
Country
Italy
City
Parma
State/Province
Emilia-Romagna
ZIP/Postal Code
43100
Country
Italy
City
Reggio Emilia
State/Province
Emilia-Romagna
ZIP/Postal Code
42100
Country
Italy
City
Trieste
State/Province
Friuli-Venezia Giulia
ZIP/Postal Code
34100
Country
Italy
City
Udine
State/Province
Friuli-Venezia Giulia
ZIP/Postal Code
33100
Country
Italy
City
Brescia
State/Province
Lombardia
ZIP/Postal Code
25125
Country
Italy
City
Milano
State/Province
Lombardia
ZIP/Postal Code
20121
Country
Italy
City
Milano
State/Province
Lombardia
ZIP/Postal Code
20122
Country
Italy
City
Torino
State/Province
Piemonte
ZIP/Postal Code
10126
Country
Italy
City
Torino
State/Province
Piemonte
ZIP/Postal Code
10149
Country
Italy
City
Bari
State/Province
Puglia
ZIP/Postal Code
70124
Country
Italy
City
Castellana Grotte
State/Province
Puglia
ZIP/Postal Code
70013
Country
Italy
City
San Giovanni Rotondo
State/Province
Puglia
ZIP/Postal Code
71013
Country
Italy
City
Cagliari
State/Province
Sardegna
ZIP/Postal Code
09042
Country
Italy
City
Messina
State/Province
Sicilia
ZIP/Postal Code
98124
Country
Italy
City
Palermo
State/Province
Sicilia
ZIP/Postal Code
90127
Country
Italy
City
Pisa
State/Province
Toscana
ZIP/Postal Code
56124
Country
Italy
City
Padova
State/Province
Veneto
ZIP/Postal Code
35128
Country
Italy
City
Verona
State/Province
Veneto
ZIP/Postal Code
37134
Country
Italy
12. IPD Sharing Statement
Citations:
PubMed Identifier
22859496
Citation
Lampertico P, Vigano M, Di Costanzo GG, Sagnelli E, Fasano M, Di Marco V, Boninsegna S, Farci P, Fargion S, Giuberti T, Iannacone C, Regep L, Massetto B, Facchetti F, Colombo M; PegBeLiver Study Group. Randomised study comparing 48 and 96 weeks peginterferon alpha-2a therapy in genotype D HBeAg-negative chronic hepatitis B. Gut. 2013 Feb;62(2):290-8. doi: 10.1136/gutjnl-2011-301430. Epub 2012 Aug 2.
Results Reference
derived
Learn more about this trial
A Study of Pegylated Interferon Alfa-2a and Lamivudine in Patients With HBeAg-Negative Chronic Hepatitis B Virus (HBV)
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