Clinical Trial Result Information

Title of Study:
A Protocol for Re-Treatment With the Combination of Peginterferon alfa-2a (40KD) and Ribavirin for Patients With Chronic Hepatitis C in Original Study NV15942 Who Relapsed Virologically After Completing 24 Weeks of Treatment

Fast Facts:

Protocol number:	WV16143
Sponsor:	F Hoffmann-La Roche Ltd
Company division:	Pharmaceutical
Product name:	PEGASYS
Generic name:	peginterferon alfa-2a (40KD)
Phase of development:	III
Therapeutic area, approved indication:	Hepatitis C, Chronic
Date of report:	4/1/2003

Clinical study summary:
This was an open-label, 48-week treatment study in patients who had previously completed a study of ribavirin (Copegus)/peginterferon alfa-2a (40KD) (PEGASYS) treatment. Patients were to commence this study on the dose of PEGASYS and ribavirin that they were receiving at the completion of the previous study (NV15942) and adjustments were made by the investigator as necessary. The maximum dose of PEGASYS was 180 μg sc once weekly, and that of ribavirin daily in split doses was 1000 mg po for patients weighing <75 kg and 1200 mg po for patients weighing ≥75 kg.

Study center(s) :
A total of 43 centers in 13 countries (Australia, Belgium, Brazil, Canada, France, Germany, Italy, New Zealand, Norway, Spain, Sweden, Taiwan, and the United States).

Objectives:
To re-treat patients (for 48 weeks) who have relapsed virologically following a 24-week course of the combination of PEGASYS and ribavirin in study NV15942.

Methodology:
Patients who were originally treated in study NV15942 and who qualified for re-treatment began PEGASYS plus ribavirin within 42 days of their original Week 48 (24 weeks off treatment) follow-up visit. Treatment in this study was for 48 weeks, with a maximum of 180 μg of PEGASYS and of 1000 or 1200 mg of ribavirin. Patients were followed for a 24-week treatment-free follow-up period for efficacy and safety.

Number of patients (planned/analyzed):
64

Diagnosis and main criteria for inclusion:
Patients with chronic hepatitis C who had received 24 weeks combination treatment in NV15942, and who had a documented end of treatment virologic response followed by a virologic relapse determined at the end of the 24 week follow-up period.

Test product, dose and mode of administration or test procedure:
PEGASYS, 180 μg/sc/qw for 48 weeks and Ribavirin, 1000 or 1200 mg (depending on body weight)/po/day in split doses

Duration of treatment:
PEGASYS: once weekly for 48 weeks; Ribavirin: twice daily for 48 weeks.

Reference therapy, dose and mode of administration or reference procedure:
Not applicable

Criteria for evaluation (efficacy, safety):
Primary efficacy parameters: (1) Sustained virologic response, defined as a single undetectable serum HCV-RNA measurement by qualitative PCR at the end of the 24-week treatment-free follow-up period (ie week 72); (2) Sustained biochemical response, defined as normal serum ALT normalized at the end of the 24-week treatment-free follow-up period (week 72). Safety parameters: Adverse events (serious adverse events and adverse events resulting in dose modification or premature withdrawal only), dose modifications, and withdrawals.

Statistical methods:
Efficacy measures (HCV-RNA and serum ALT) and safety parameters (see above) were summarized descriptively.

Summary (efficacy, safety, other results):
Efficacy - A sustained virologic response was achieved by 55% of patients (63% of patients infected with HCV genotype non-1 and 51% of patients infected with genotype 1). A sustained biochemical response was achieved by 75% of patients (79% of patients with HCV genotype non-1 and 73% of patients with HCV genotype 1). Of the patients who achieved an end-of-treatment virologic response, 65% (75% of patients with HCV genotype non-1 and 61% of patients with HCV genotype 1) maintained their response and achieved a sustained virologic response. Of the patients who achieved an end-of-treatment biochemical response, 89% (100% of patients with HCV genotype non-1 and 85% of patients with HCV genotype 1) maintained their response and achieved a sustained biochemical response.

Safety - Serious adverse events, adverse events that led to withdrawal, or adverse events that led to dose modification were reported by 19% of patients. The most frequently reported of these adverse events were fatigue (5%) and abdominal pain (3%). Five patients (8%) had serious adverse events, three of which (anemia, cervicitis, and transient ischemic attack) were considered by the investigator to be related to treatment. Only 2 patients (3%) withdrew from treatment because of an adverse event (cervicitis and cellulitis). The dose of PEGASYS was modified in 27% of patients, mainly because of laboratory abnormalities, primarily neutropenia, but no patients withdrew due to laboratory abnormalities. The ribavirin dose was modified in 16% of patients, mainly because of adverse events, primarily anemia. No patient died during the study.

Conclusions:
The results of this study suggest that a majority of patients who relapse after an initial 24 weeks of treatment with PEGASYS and ribavirin combination therapy can be successfully re-treated with PEGASYS and ribavirin combination therapy for 48 weeks to achieve sustained viral clearance. The safety profile of these patients is consistent with what has been reported previously.

Publications (references, if available):
1) Berg C, Goncales F, Bernstein D et al Re-treatment of Chronic Hepatitis C Patients After Relapse: Efficacy of Peginterferon alfa-2a (40KD) and Ribavirin. Paper accepted by J.Vir. Hepatitis 2) Goncales F, Bernstein D, Berg C et al Peginterferon alfa-2a (40KD) (Pegasys) plus ribavirin in chronic hepatitis C: retreatment of patients who relapsed virologically after 24 weeks of therapy. Hepatology 36:361A Abstract 794 (2002).