Clinical Trial Result Information

Protocol number
IT8005

Title of Study
Efficacy and safety of peg-interferon alfa-2a (Pegasys) monotherapy and combination therapy with ribavirin in the treatment of genotype 4 Saudi chronic active hepatitis C patients

Sponsor
Hoffmann-La Roche Ltd

Company division
Pharmaceutical

Product name
PEGASYS

Generic name
peginterferon alfa-2a (40KD)

Therapeutic area
Hepatitis C, Chronic

Clinical study summary
This randomized, multicenter study evaluated the efficacy and safety of peginterferon alfa-2a (40KD) (PEGASYS) in Saudi patients with genotype 4 chronic hepatitis C (CHC). Patients were divided into 3 treatment groups: Group A received PEGASYS + ribavirin, Group B received PEGASYS;monotherapy and Group C received interferon alfa-2a (Roferon-A) + ribavirin. After 48 weeks of treatment, a 24 week follow-upperiod was observed.

Study center(s)
6 in Saudi Arabia.

Phase of development
IV

Objectives
(1) To determine the efficacy of PEGASYS in the treatment of patients with genotype 4 CHC in Saudi Arabia; (2) To compare sustained response to treatment for genotype 4 CHC using PEGASYS and ribavirin combination therapy compared with Roferon-A monotherapy; (3) To compare the effect of PEGASYS and ribavirin combination therapy in patients with genotype 4 CHC compared with PEGASYS monotherapy; (4) To determine the side effects and long-term safety of PEGASYS in the treatment of Saudi patients with genotype 4 CHC.

Methodology
Patients were randomized to receive PEGASYS 180μg qw + ribavirin 400mg bid (Group A), PEGASYS 180μg qw (Group B) or Roferon-A 4.5MIU tiw + ribavirin 400mg bid (Group C). Quantitative polymerase chain reaction (PCR) sequencing was performed at 0, 12, 48, and 72 weeks. Biochemical and hematologic tests were performed on blood taken at intervals up to 72 weeks. At the end of 48 weeks, a second liver biopsy was performed on all patients. Knodell scores were taken by 2 histopathologists scoring the slides independently in a blind assay and the results compared with those of the initial biopsy

Number of patients (planned/analyzed)
180 enrolled.

Diagnosis and main criteria for inclusion
180 adult (≥ 18 years of age) treatment-naïve Saudi patients with genotype 4 CHC virus infection.

Clinical diagnosis: Patients with genotype CHC with or without compensated liver cirrhosis defined by modified Child-Pugh Grade A classification. Persistently elevated (>1.5 times the upper limit of normal) serum alanine aminotransferase levels (ALT), and other clinical features for chronic hepatitis.

Test product, dose and mode of administration or test procedure
PEGASYS 180 μg/sc/week. Ribavirin 400mg /po/bid

Duration of treatment
48 weeks

Reference therapy, dose and mode of administration or reference procedure
Roferon-A 4.5 MIU/sc/3 times week.

Criteria for evaluation (efficacy, safety)
Efficacy: Samples for quantitative PCR (HCV Amplicor, Roche) testing were taken and tested at Weeks 0, 12, 48, and 72 to establish virologic response to treatment in all patients. Virological response was defined as ≥ 2-log drop or HCV-RNA clearance

Biochemistry: Liver function tests, including serum bilirubin, ALT, aspartate aminotransferase, alkaline phosphatase, and γ-glutamyl transpeptidase were conducted. Kidney function tests were performed periodically,and. thyroid function testing was performed routinely.

Hematology: Hematologic parameters were monitored throughout the study period.

Summary (efficacy, safety, other results)
Efficacy – Early virologic responses (≥2-log decrease or HCV-RNA clearance) at Week 12 were 77%, 60%, and 43% in Groups A, B, and C, respectively. End-of-treatment responses (Week 48) for these groups were 67%, 59%, and 37%, respectively. Sustained virologic responses (SVRs) (Week 72) were 50%, 28%, and 30%, respectively. Among Week 12 early responders, SVRs were 65.2% and 47.2% in the 2 PEGASYS groups A and B, respectively) and sustained biochemical responses were 69.6% and 69.4% in these groups.

Safety – Twelve patients (6.7%) withdrew from the study because of various adverse events, ie, alopecia, thyroiditis, esophageal varices, tonic convulsion, encephalopathy, and depression. In Group A, 7 patients withdrew from the study; in Group B, 4 patients and in Group C, 1 patient.

Conclusions
A 100% negative predictive value among non-responders was observed for all treatment groups at early virologic response at Week 12. Despite the use of a low dose of ribavirin (400 mg bid), an enhanced SVR of 50% (65% in early responders) was determined for the combination of PEGASYS plus ribavirin. A comparatively low relapse rate was observed in patients treated with PEGASYS plus ribavirin. The results of the study indicate that patients infected with genotype 4 CHC can be safely and effectively treated with PEGASYS plus ribavirin.

Date of report
12/12/2005