A Study of Pegasys (Peginterferon Alfa-2a) Added to Nucleos(t)Ide Analogue Treatment in Patients With HBeAg-Negative Chronic Hepatitis B Genotype D Showing Stable HBV DNA Suppression

Hepatitis B, Chronic Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01706575
• Other study ID #: ML28262
• Secondary ID: 2012-000080-25
• Status: Completed
• Phase: Phase 2
• First received: October 10, 2012
• Last updated: March 1, 2016
• Start date: April 2013
• Est. completion date: October 2015

Study information

• Verified date: March 2016
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Agenzia Italiana del Farmaco (AIFA)
• Study type: Interventional

Clinical Trial Summary

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 patients with HBeAg-negative chronic hepatitis B genotype D showing stable HBV DNA suppression. After a 12-week Lead-in period on treatment with NA, patients 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 patients will continue their NA treatment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: October 2015
• Est. primary completion date: October 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Adult patients, 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 HAV, HCV, HDV, 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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• nucleos(t)ide analogues
Adenovir, entecavir, lamivudine or tenofovir
• peginterferon alfa-2a [Pegasys]
180 mcg subcutaneously weekly, 48 weeks

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients with serum HBsAg decrease >/= 50% from baseline to the end of the combination treatment Pegasys plus NA (Study Week 48)		approximately 2.5 years	No
Secondary	Proportion of patients with HBsAg decrease >/=1 log10 IU/ml from baseline to Week 48		approximately 2.5 years	No
Secondary	Change in HBsAg levels		from baseline to Week 96	No
Secondary	Proportion of patients with HBsAg </= 0.05 UI/ml at Week 48		approximately 2.5 years	No
Secondary	Proportion of patients with HBsAg </= 0.05 UI/ml at Week 72		approximately 2.5 years	No
Secondary	Proportion of patients with HBsAg </= 0.05 UI/ml at Week 96		approximately 2.5 years	No
Secondary	HBsAg levels according to IL28B genotypes		approximately 2.5 years	No
Secondary	HBsAg levels according to IP-10 serum levels		approximately 2.5 years	No
Secondary	Safety: Incidence of adverse events		approximately 2.5 years	No