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Implications of host polymorphism IL28b for drug development and patient care - Mark Sulkowski MD
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Mark Sulkowski, MD
Associate Professor of Medicine
Medical Director, Viral Hepatitis Center
Johns Hopkins University
Baltimore, Maryland USA
Reported by Jules Levin
The 5th International Workshop on Clinical Pharmacology of Hepatitis Therapy
Boston, MA June 23-24, 2010
This slide provides the conceptual framework on which the clinical data can be viewed.
In order to achieve SVR, the total body viral burden needs to be below 1 copy, which corresponds to plasma HCV RNA levels below 10-5 IU/mL. A mixed population at baseline is assumed, (just as in 102) such that total body eradication requires elimination of both WT and resistant variants.
During treatment, HCV RNA declines in a biphasic manner .
This results in a rapid elimination of WT by TVR in approximately 8-12 weeks, based on the 102 data, and additional sequence data from the 104 study that that I did not show, and a less rapid elimination of variants by Peg/RBV.
Our relapse data (which I'll show in a minute) suggests that the variant elimination can occur with 24 weeks of treatment. As you know, with SOC 48 weeks is required in most patients to eradicate virus.
AS we consider treatment regimens with shorter TVR durations, we will take this into account, along with the safety data in designing a regimen to test. We want to avoid increasing the breakthrough and relapse rates.
87% of patients with IL28b cc mutation achieved undetectable viral load by week 12 (cEVR)
The SPRINT-1 trial is a phase 2 trial designed to evaluate the optimal strategy for administrating the protease inhibitor boceprevir in treatment-naive patients with HCV genotype 1
28 weeks vs 48 weeks
Lead-in vs no lead-in
Standard-dose vs low-dose RBV
The study design includes the following arms
Lead-in dosing strategy : PEG-IFN α-2b 1.5 µg/kg + RBV 800-1400 mg x 4 weeks followed by PEG-IFN α-2b 1.5 µg/kg + RBV 800-1400 mg +
boceprevir 800 mg TID for 24 weeks or 44 weeks
No lead-in dosing strategy: PEG-IFN α-2b 1.5 µg/kg + RBV 800-1400 mg + boceprevir 800 mg TID for 28 weeks or 48 weeks
Low-dose RBV dosing strategy: PEG-IFN α-2b 1.5 µg/kg + RBV 400-1000 mg + boceprevir 800 mg TID for 48 weeks
Control: PEG-IFN α-2b 1.5 µg/kg + RBV 800-1400 mg for 48 weeks
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