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Completed

NCT Number: NCT01095835

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

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.

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Key information

Conditions

Hepatitis B, Chronic Blood-Borne Infections Chronic Disease Communicable Diseases DNA Virus Infections Digestive System Diseases Disease Attributes Hepadnaviridae Infections Hepatitis Hepatitis B Hepatitis, Chronic Hepatitis, Viral, Human Infections Liver Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Virus Diseases

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Bari, Apulia, Italy

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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).

Treatment and study plan

Pegylated interferon (PEG-IFN) alfa-2a, 180 mcg

Drug

PEG-IFN alfa-2a 180 micrograms (mcg) was administered subcutaneously, once weekly from Week 0 to 48.

Other names: Pegasys®

Pegylated interferon (PEG-IFN) alfa-2a, 135 mcg

Drug

PEG-IFN alfa-2a 135 mcg was administered subcutaneously, once weekly from Week 49 to 96.

Other names: Pegasys®

Lamivudine (LAM)

Drug

Lamivudine 100 milligrams (mg) was administered orally, daily from Week 0 to 48.

Primary outcomes

  1. 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.

Secondary outcomes

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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.

Other outcomes

  1. 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

  2. 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

  3. 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.

  4. 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.

Sponsors and collaborators

Lead sponsor

Hoffmann-La Roche

Industry

Registry information

Official study 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

Important dates

Study start
2005
Primary completion
2010
Study completion
2010
First posted
Mar 30, 2010
Registry last updated
Nov 3, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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