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Fw: NATAP/DDW: WIN-R Study, Outcomes by G2-3/Viral load

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  • Alley Pat
    NATAP http://natap.org/ ... Differences In Treatment Outcome To Antiviral Therapy Based On Genotype And Viral Load In Hepatitis C Genotypes 2 And 3 In The
    Message 1 of 1 , Jun 3, 2006
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      Differences In Treatment Outcome To Antiviral Therapy Based On Genotype And Viral Load In Hepatitis C Genotypes 2 And 3 In The WIN-R Trial

      Reported by Jules Levin
      DDW, May 2006, Los Angeles

      R.S. Brown, Jr., I.M. Jacobson, N. Afdhal, B. Freilich, M.P. Pauley, F. Regenstein, S. Flamm, P. Kwo,
      L. Griffel, C.A. Brass, & the WIN-R Study Group

      WIN-R Study: final results of Weight-Based dosing study of ...Here is link to report on WIN-R Study presentation at AASLD Nov 2005 written by Jules Levin
      www.natap.org/2005/AASLD/aasld_59.htm

      WIN-R Trial: Background
      Weight-Based Interferon and Ribavirin Trial
      o Peginterferon (PEG-IFN) alfa-2b 1.5 µg/kg/week + ribavirin (RBV) 800 mg/day was superior to two other regimens using RBV 1000-1200 mg/day in a pivotal trial
      - Manns et al, Lancet 2001
      o Regression analysis showed a linear relationship between RBV dose in mg/kg and sustained virological response (SVR) supporting the use of weight-based dosing of RBV
      o A large prospective trial - WIN-R - comparing RBV doses was designed to address fixed dose RBV 800 mg vs weight-based RBV dosing

      WIN-R: G 2/3 Analysis
      o Patients with G 2/3 chronic hepatitis C have high SVR rates with PEG-IFN alfa and RBV
      o Require shorter duration of treatment
      o May not need high dose of RBV
      o Optimal dosing of RBV and differences between SVR in G 2/3 patients is undefined

      Objective of analysis
      To analyze the efficacy of PEG-IFN alfa-2b plus RBV in patients with HCV G 2/3 in the WIN-R trial

      WIN-R Trial
      o US multicenter, randomized, open-label, investigator-initiated trial between 12/2000 and 6/2005
      o Randomized treatment-naive adults stratified by genotype (1 and non-1) and
      fibrosis
      o 25 regional investigators, 225 sites
      o Nearly 5000 patients; 1829 patients with G 2/3
      o Central lab (SPRI) for quantitative PCR for HCV RNA
      o Lower limit of detection was 29 IU/ml
      o 0, 24, 48, 72 weeks



      Study Populations and Analyses
      o Intent-to-treat (ITT) population
      o All subjects who received at least one dose of study drug
      o Used for safety analysis
      o Primary efficacy population
      o All subjects who received at least one dose of study drug and weighed â?¥65 kg
      o Used for primary efficacy end point - SVR
      o Completers analysis population
      o All subjects who received at least one dose of study drug, completed the study, and had end-of-treatment data available

      Study Enrollment and Randomization:
      HCV G 2/3 Subjects


      WIN-R G 2/3 Population:
      Demographics

      ITT population (n = 1829).

      SVR in HCV G 2/3 Subjects
      by Treatment Duration

      ITT population (n = 1829).
      Jacobson I., et al. AASLD 2005

      SVR in HCV G 2/3 24-Week Subjects >/= 65 kg
      by Genotype

      Primary efficacy population (>/=65 kg).
      *P = 0.08; G2 vs G3.

      SVR in HCV G 2/3 Subjects >/= 65 kg
      by Treatment Duration

      Primary efficacy population (â?¥65 kg).
      Drop-out = all discontinuations regardless of reason (eg, withdrawal, subject compliance, adverse event, missing data).

      SVR in HCV G 2/3 24-Week Subjects >/= 65 kg
      by Viral Load

      Subjects from the primary efficacy population (>/=65 kg) with viral load data available.
      High viral load (HVL) = >600,000 IU/mL HCV RNA.
      Low viral load (LVL) = <600,000 IU/mL HCV RNA.
      P = NS, all comparisons.

      Relapse Rates* in Subjects >/= 65 kg
      by WBD vs FD

      Subjects from the primary efficacy population (>/= 65 kg) with viral load data available.
      o Relapse rates calculated using data from subjects who were negative at end-of-treatment but positive at FU.

      Secondary Completers Analysis of SVR

      * Subjects who dropped out of the study or lost to FU were considered non-responders.
      â? P < 0.05, FD vs WBD.
      â?¡ Completers analysis includes all subjects who completed the study.
      § RBV >10.6 mg/kg.

      Secondary Completers Analysis of
      SVR and Relapse Rate in Genotype 2
      by Viral Load and Treatment Duration


      Subjects from the primary efficacy population (>/= 65 kg) with viral load data available.
      P-values are based on logistic regression with FD/WBD, duration, presence of advanced fibrosis/cirrhosis in the model.
      P = NS, all comparisons.

      Secondary Completers Analysis of
      SVR and Relapse Rate in Genotype 3
      by Viral Load and Treatment Duration


      Subjects from the primary efficacy population (â?¥65 kg) with viral load data available.
      P-values are based on logistic regression with FD/WBD, duration, presence of advanced fibrosis/cirrhosis in the model.
      P = NS, all comparisons.

      SVR in HCV G 2 Subjects >65 kg
      F 0/1/2 vs F 3/4, ITT Population

      HVL = >600,000 IU/mL
      LVL = <600,000 IU/mL

      SVR in HCV G 3 Subjects >65 kg
      F 0/1/2 vs F 3/4, ITT Population


      ITT Overall SVR in HCV Genotypes
      2/3 > 65 kg

      Overall SVR = Combined 24- and 48-week data
      Jacobson I., et al. AASLD 2005.

      SVR in HCV Genotype 3, 24 Weeks Tx
      PEG-IFN a-2b + ribavirin


      SVR in HCV 3
      HVL vs LVL Subjects > 65 kg



      WIN-R: Genotype 2/3 Conclusions
      o 24 weeks of PEG-IFN alfa-2b + RBV was sufficient for HCV G 2/3 patients

      o PEG-IFN alfa-2b + fixed-dose (800 mg) RBV for 24 weeks was sufficient for Genotype 2 patients

      o Overall, G 2 patients had higher SVR rates from treatment with PEG-IFN alfa-2b + RBV than G 3 patients

      o Weight-adjusted doses of RBV may benefit patients with G 3 and high viral load

      o Treatment with PEG-IFN alfa-2b + RBV resulted in consistently low relapse rates in G 2/3 patients treated for either 24 weeks or 48 weeks

      o No clear differences were seen in SVR and relapse rates for G3 HVL with longer duration of treatment

      o Further research is needed to define optimal treatment for G3 HVL








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