Hepatitisweb study

Hepatitisweb study

Duration and Dose Finding Peginterferon alfa-2a + Ribavirin

Phase 3

Treatment Naïve, Chronic HCV

Randomized study of low-dose versus weight based ribavirin and 24 versus 48 weeks of therapy

Hadziyannis SJ, et. al. Ann Intern Med. 2004;140:346-55.

Hepatitisweb study

*Ribavirin dose: Ribavirin 1000 mg/day for Wt <75 kg, 1200 mg/day for Wt ≥75 kg

Peginterferon alfa-2a + Ribavirin for Chronic HCVTreatment Duration and Ribavirin Dose

• Study- Randomized, double-blind trial, with 2 x 2 factorial design

• Subjects- N = 1311 with chronic hepatitis C (1284 treated)- Treatment naïve adult patients; 58% genotype 1 - Serum ALT above upper limit of normal x prior 6 months

• Regimens - Peginterferon alfa-2a: 180 µg/wk + Ribavirin: 800 mg/day x 24 wks - Peginterferon alfa-2a: 180 µg/wk + *Ribavirin: 1000-1200 mg/day x 24 wks - Peginterferon alfa-2a: 180 µg/wk + Ribavirin: 800 mg/d x 48 weeks- Peginterferon alfa-2a: 180 µg/wk + *Ribavirin: 1000-1200 mg/day x 48 wks

• Primary Endpoint- Undetectable serum HCV RNA at end of treatment (ETR) - Undetectable serum HCV RNA 24 wks after cessation of treatment (SVR)

Source: Hadziyannis SJ, et. al. Ann Intern Med. 2004;140:346-55.

Hepatitisweb study

Peginterferon alfa-2a + Ribavirin (low dose)(n = 214)

Peginterferon alfa-2a + Ribavirin (low dose)(n = 365)

Peginterferon alfa-2a + Ribavirin (weight-based dose)(n = 288)

Peginterferon alfa-2a + Ribavirin (weight-based dose)(n = 444)

48 720 12

Randomize

Week 24

Source: Hadziyannis SJ, et. al. Ann Intern Med. 2004;140:346-55.

Peginterferon alfa-2a + Ribavirin for Chronic HCVTreatment Duration and Ribavirin Dose

SVR24

SVR24

SVR24

SVR24

Hepatitisweb study

Genotype 1 Genotypes 2 or 30

20

40

60

80

100

29

84

42

81

41

79

52

80

PEG + RBV (low dose) x 24 weeks PEG + RBV (weight-based dose) x 24 weeks

PEG + RBV (low dose) x 48 weeks PEG + RBV (weight-based dose) x 48 weeks

Genotype

Patie

nts

with

SVR

(%)

Peginterferon alfa-2a + Ribavirin for Chronic HCVTreatment Duration and Ribavirin Dose

SVR24 Rates, by Regimen

Source: Hadziyannis SJ, et. al. Ann Intern Med. 2004;140:346-55.

n = 101 n = 118 n = 250 n = 271 n = 96 n = 144 n = 99 n = 153

Hepatitisweb study

All Patients Low Viral Load_x000d_(≤2 mil-

lion)

High Viral Load_x000d_(>2 mil-

lion)

0

20

40

60

80

10084 85 8481 83 8079

88

7480 77

82

Peginterferon + Ribavirin (low dose) x 24 weeks Peginterferon + Ribavirin (weight-based dose) x 24 weeks Peginterferon + Ribavirin (low dose) x 48 weeks Peginterferon + Ribavirin (weight-based dose) x 48 weeks

Patie

nts

with

SVR

(%)

Peginterferon alfa-2a + Ribavirin for Chronic HCVTreatment Duration and Ribavirin Dose

Rates of SVR with Different Peginterferon + Ribavivirn Regimens

Source: Hadziyannis SJ, et. al. Ann Intern Med. 2004;140:346-55.

(≤ 2 x 106 copies/ml) (> 2 x 106 copies/ml)

Hepatitisweb studySource: Hadziyannis SJ, et. al. Ann Intern Med. 2004;140:346-55.

Peginterferon alfa-2a + Ribavirin for Chronic HCVTreatment Duration and Ribavirin Dose

Conclusion: “Treatment with peginterferon-alpha2a and ribavirin may be individualized by genotype. Patients with HCV genotype 1 require

treatment for 48 weeks and a standard dose of ribavirin; those with HCV genotypes 2 or 3 seem to be adequately treated with a low dose of ribavirin for 24 weeks.”

Hepatitisweb study

Hepatitisweb study

This slide deck is from the University of Washington’s Hepatitis C Online and Hepatitis Web Study projects.

Hepatitis C Onlinewww.hepatitisc.uw.edu

Hepatitis Web Studyhttp://depts.washington.edu/hepstudy/

Funded by a grant from the Centers for Disease Control and Prevention.