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

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ClinicalTrials.gov Identifier: NCT01095835
Recruitment Status : Completed
First Posted : March 30, 2010
Results First Posted : November 3, 2016
Last Update Posted : November 3, 2016
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Description
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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.

Condition or disease Intervention/treatment Phase
Hepatitis B, Chronic Drug: Pegylated interferon (PEG-IFN) alfa-2a, 180 mcg Drug: Pegylated interferon (PEG-IFN) alfa-2a, 135 mcg Drug: Lamivudine (LAM) Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 131 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : February 2005
Actual Primary Completion Date : January 2010
Actual Study Completion Date : January 2010

Resource links provided by the National Library of Medicine


Arms and Interventions
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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 Name: 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 Name: 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 Name: 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 Name: 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 Name: Pegasys®

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


Outcome Measures
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Primary Outcome Measures :
  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 Outcome Measures :
  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 Outcome Measures:
  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.


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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).
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01095835


Locations
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Italy
Caserta, Campania, Italy, 81100
Napoli, Campania, Italy, 80131
Napoli, Campania, Italy, 80135
Bologna, Emilia-Romagna, Italy, 40138
Parma, Emilia-Romagna, Italy, 43100
Reggio Emilia, Emilia-Romagna, Italy, 42100
Trieste, Friuli-Venezia Giulia, Italy, 34100
Udine, Friuli-Venezia Giulia, Italy, 33100
Brescia, Lombardia, Italy, 25125
Milano, Lombardia, Italy, 20121
Milano, Lombardia, Italy, 20122
Torino, Piemonte, Italy, 10126
Torino, Piemonte, Italy, 10149
Bari, Puglia, Italy, 70124
Castellana Grotte, Puglia, Italy, 70013
San Giovanni Rotondo, Puglia, Italy, 71013
Cagliari, Sardegna, Italy, 09042
Messina, Sicilia, Italy, 98124
Palermo, Sicilia, Italy, 90127
Pisa, Toscana, Italy, 56124
Padova, Veneto, Italy, 35128
Verona, Veneto, Italy, 37134
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01095835    
Other Study ID Numbers: ML18253
First Posted: March 30, 2010    Key Record Dates
Results First Posted: November 3, 2016
Last Update Posted: November 3, 2016
Last Verified: March 2016
Additional relevant MeSH terms:
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Hepatitis A
Hepatitis B
Hepatitis B, Chronic
Hepatitis
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Infections
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Blood-Borne Infections
Communicable Diseases
Hepadnaviridae Infections
 DNA Virus Infections
Hepatitis, Chronic
Interferons
Lamivudine
Peginterferon alfa-2a
Interferon-alpha
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents