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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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01706575
First received: October 10, 2012
Last updated: June 24, 2016
Last verified: June 2016
  Purpose
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.

Condition Intervention Phase
Hepatitis B, Chronic
Drug: Pegylated Interferon (Peginterferon) Alfa-2a
Drug: Nucleos(t)ide Analogues (NA)
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • Efficacy: Percentage of Participants With Serum Hepatitis B Surface Antigen (HBsAg) Decrease >/= 50% From Baseline at End of the Combination Treatment (Week 48) [ Time Frame: Baseline and Week 48 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Week 24, 72 and 96 ] [ Designated as safety issue: No ]
  • Efficacy: Percentage of Participants With HBsAg Decrease >/=1 log10 IU/ml From Baseline to Week 48 [ Time Frame: Baseline and Week 48 ] [ Designated as safety issue: No ]
  • Efficacy: Percentage of Participants With Serum HBsAg Loss at Week 48, 72 and 96 [ Time Frame: Week 48, 72 and 96 ] [ Designated as safety issue: No ]
    HBsAg loss is defined as HBsAg less than or equal to (</=) 0.05 IU/ml.

  • Efficacy: HBsAg Levels According to Interleukin 28B (IL28B) Genotypes [ Time Frame: Baseline and Week 48 ] [ Designated as safety issue: No ]
  • Efficacy: HBsAg Levels According to Interferon-Inducible Protein 10 (IP-10) Serum Levels [ Time Frame: Baseline and Week 48 ] [ Designated as safety issue: No ]
  • Safety: Number of Participants With Adverse Events (AE) [ Time Frame: Baseline up to Week 48 ] [ Designated as safety issue: No ]
    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.


Enrollment: 76
Study Start Date: January 2013
Study Completion Date: November 2014
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pegylated Interferon (Peginterferon) Alfa-2a
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.
Drug: Pegylated Interferon (Peginterferon) Alfa-2a
Peginterferon alfa-2a 180 mcg, subcutaneously (SC) once weekly for 48 weeks.
Other Name: Pegasys
Drug: Nucleos(t)ide Analogues (NA)
Nucleos(t)ide analogues includes adefovir, entecavir, lamivudine or tenofovir.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01706575

Locations
Italy
Napoli, Campania, Italy, 80131
Bologna, Emilia-Romagna, Italy, 40138
Udine, Friuli-Venezia Giulia, Italy, 33100
Roma, Lazio, Italy, 00133
Roma, Lazio, Italy, 00161
Genova, Liguria, Italy, 16132
Milano, Lombardia, Italy, 20122
Torino, Piemonte, Italy, 10126
Foggia, Puglia, Italy, 71100
Cagliari, Sardegna, Italy, 09042
Messina, Sicilia, Italy, 98124
Palermo, Sicilia, Italy, 90127
Pisa, Toscana, Italy, 56124
Padova, Veneto, Italy, 35128
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01706575     History of Changes
Other Study ID Numbers: ML28262  2012-000080-25 
Study First Received: October 10, 2012
Results First Received: June 24, 2016
Last Updated: June 24, 2016
Health Authority: Italy: Agenzia Italiana del Farmaco (AIFA)

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis, Chronic
Hepatitis B
Hepatitis B, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Interferons
Peginterferon alfa-2a
Interferon-alpha
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 29, 2016