A Study of Pegylated Interferon Alfa-2a and Lamivudine in Patients With HBeAg-Negative Chronic Hepatitis B Virus (HBV)

September 15, 2016 updated by: Hoffmann-La Roche

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

131

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
    • Campania
      • Caserta, Campania, Italy, 81100
      • Napoli, Campania, Italy, 80131
      • Napoli, Campania, Italy, 80135
    • Emilia-Romagna
      • Bologna, Emilia-Romagna, Italy, 40138
      • Parma, Emilia-Romagna, Italy, 43100
      • Reggio Emilia, Emilia-Romagna, Italy, 42100
    • Friuli-Venezia Giulia
      • Trieste, Friuli-Venezia Giulia, Italy, 34100
      • Udine, Friuli-Venezia Giulia, Italy, 33100
    • Lombardia
      • Brescia, Lombardia, Italy, 25125
      • Milano, Lombardia, Italy, 20122
      • Milano, Lombardia, Italy, 20121
    • Piemonte
      • Torino, Piemonte, Italy, 10126
      • Torino, Piemonte, Italy, 10149
    • Puglia
      • Bari, Puglia, Italy, 70124
      • Castellana Grotte, Puglia, Italy, 70013
      • San Giovanni Rotondo, Puglia, Italy, 71013
    • Sardegna
      • Cagliari, Sardegna, Italy, 09042
    • Sicilia
      • Messina, Sicilia, Italy, 98124
      • Palermo, Sicilia, Italy, 90127
    • Toscana
      • Pisa, Toscana, Italy, 56124
    • Veneto
      • Padova, Veneto, Italy, 35128
      • Verona, Veneto, Italy, 37134

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: PEG-IFN48
Treatment with PEG-IFN in participants with HBeAg-negative chronic hepatitis B virus for 48 weeks.
Drug: Pegylated interferon (PEG-IFN) alfa-2a, 180 mcg
PEG-IFN alfa-2a 180 micrograms (mcg) was administered subcutaneously, once weekly from Week 0 to 48.
Other Names:
  • Pegasys®
Experimental: PEG-IFN96
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).
Drug: Pegylated interferon (PEG-IFN) alfa-2a, 180 mcg
PEG-IFN alfa-2a 180 micrograms (mcg) was administered subcutaneously, once weekly from Week 0 to 48.
Other Names:
  • Pegasys®
Drug: Pegylated interferon (PEG-IFN) alfa-2a, 135 mcg
PEG-IFN alfa-2a 135 mcg was administered subcutaneously, once weekly from Week 49 to 96.
Other Names:
  • Pegasys®
Experimental: PEG-IFN+LAM96
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).
Drug: Pegylated interferon (PEG-IFN) alfa-2a, 180 mcg
PEG-IFN alfa-2a 180 micrograms (mcg) was administered subcutaneously, once weekly from Week 0 to 48.
Other Names:
  • Pegasys®
Drug: Pegylated interferon (PEG-IFN) alfa-2a, 135 mcg
PEG-IFN alfa-2a 135 mcg was administered subcutaneously, once weekly from Week 49 to 96.
Other Names:
  • Pegasys®
Drug: Lamivudine (LAM)
Lamivudine 100 milligrams (mg) was administered orally, daily from Week 0 to 48.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants Achieving the Combined Response at the End of the Follow-up Period
Time Frame: At the end of the 48-week follow-up period at Week 144
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.
At the end of the 48-week follow-up period at Week 144

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants Achieving the Combined Response at the End of Treatment
Time Frame: At end of treatment at Week 48 or 96 depending on the study arm
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.
At end of treatment at Week 48 or 96 depending on the study arm
Percentage of Participants Achieving the Combined Response at 24 Weeks of Follow-up
Time Frame: At the end of 24 weeks of follow-up at Week 120
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.
At the end of 24 weeks of follow-up at Week 120
Percentage of Participants Achieving Combined Response Using a Cut-Off for HBV-DNA Levels 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
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.
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
Percentage of Participants Achieving Histological Response
Time Frame: At the end of the 48-week follow-up period at Week 144
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.
At the end of the 48-week follow-up period at Week 144
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
At the end of treatment at Week 48 or 96 depending on the study arm
Percentage of Participants With Lamivudine Genotype Resistance During PEG-IFN+LAM96 Combined Therapy
Time Frame: At the end of the treatment period at Week 96
Lamivudine resistance mutations were assessed by detection of the following mutations: rtL80V, rtL80I, rtV173G, rtV173L, rtL180M, rtA181T, rtA181V, rtM204V, rtM204I and rtN236T.
At the end of the treatment period at Week 96

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
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
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
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
Percentage of Participants With HBV-DNA Below Limit of 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
HBV-DNA limit < 6 IU/mL was defined as below quantification.
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
Percentage of Participants With Loss of Hepatitis B Surface Antigen (HbsAg) and Hepatitis B Surface Antibodies (Anti-HBs) Seroconversion
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
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.
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hoffmann-La Roche

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2005

Primary Completion (Actual)

January 1, 2010

Study Completion (Actual)

January 1, 2010

Study Registration Dates

First Submitted

March 26, 2010

First Submitted That Met QC Criteria

March 26, 2010

First Posted (Estimate)

March 30, 2010

Study Record Updates

Last Update Posted (Estimate)

November 3, 2016

Last Update Submitted That Met QC Criteria

September 15, 2016

Last Verified

March 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ML18253

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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