Combination therapy for eradicating detectable HCV-RNA in patients having chronic hepatitis C infection

Abstract

There is disclosed a method for treating a patient having chronic hepatitis C infection to eradicate detectable HCV-RNA involving a combination therapy using a therapeutically effective amount of ribavirin and a therapeutically effective amount of interferon-alpha for a time period of from 20 up to 80 weeks.

1 . A method of treating a patient having chronic hepatitis C infection to eradicate detectable HCV-RNA comprising administering a therapeutically effective amount of ribavirin and a therapeutically effective amount of interferon-alpha for a time period of 20 to 30 weeks, such that at least about 30% of the patients having no detectable HCV-RNA at the end of said 20 to 30 week period also have no detectable HCV-RNA for at least 24 weeks after the end of said administration.  
     
     
         2 . The method of  claim 1 , wherein at least about 40% of the patients having no detectable HCV-RNA at the end of said 20 to 30 week period also have no detectable HCV-RNA for at least 24 weeks after the end of said administration.  
     
     
         3 . The method of  claim 1 , wherein the amount of ribavirin administered is from 400 to 1200 mg per day.  
     
     
         4 . The method of  claim 1 , wherein the amount of ribavirin administered is from 800 to 1200 mg per day.  
     
     
         5 . The method of  claim 3 , wherein the interferon-alpha administered is selected from interferon alpha-2a, interferon alpha-2b, a consensus interferon, a purified interferon alpha product or a pegylated interferon-alpha.  
     
     
         6 . The method of  claim 3 , wherein the interferon-alpha is selected from interferon alpha-2a, interferon alpha-2b, or a purified interferon alpha product and the amount of interferon-alpha administered is from 2 to 10 million IU per week on a weekly, TIW, QOD or daily basis.  
     
     
         7 . The method of  claim 4 , wherein the interferon-alpha administered is interferon-alpha-2b and the amount of interferon-alpha is administered 3 million IU TIW.  
     
     
         8 . The method of  claim 3 , wherein the interferon-alpha administered is consensus interferon and the amount of interferon-alpha administered is from 1 to 20 micrograms per week on a weekly, TIW, QOD or daily basis.  
     
     
         9 . The method of  claim 3 , wherein the interferon-alpha administered is a pegylated interferon alpha-2b and the amount of interferon-alpha administered is from 0.5 to 2.0 micrograms/kilogram per week on a weekly, TIW, QOD or daily basis.  
     
     
         10 . The method of  claim 3 , wherein the interferon-alpha administered is a pegylated interferon alpha-2a and the amount of interferon-alpha administered is from 20 to 250 micrograms/kilogram per week on a weekly, TIW, QOD or daily basis.  
     
     
         11 . A method of treating a patient having chronic hepatitis C infection to eradicate detectable HCV-RNA comprising administering a therapeutically effective amount of ribavirin and a therapeutically effective amount of interferon-alpha for a time period of 40 to 50 weeks, such that at least about 40% of the patients having no detectable HCV-RNA at the end of said 40 to 50 week period also have no detectable HCV-RNA for at least 24 weeks after the end of said administration.  
     
     
         12 . The method of  claim 11 , wherein at least about 50% of the patients having no detectable HCV-RNA at the end of said 40 to 50 week period also have no detectable HCV-RNA for at least 24 weeks after the end of said administration.  
     
     
         13 . The method of  claim 11 , wherein the amount of ribavirin administered is from 400 to 1200 mg per day.  
     
     
         14 . The method of  claim 11 , wherein the amount of ribavirin administered is from 800 to 1200 mg per day.  
     
     
         15 . The method of  claim 13 , wherein the interferon-alpha administered is selected from interferon alpha-2a, interferon alpha-2b, a consensus interferon, a purified interferon alpha product or a pegylated interferon-alpha.  
     
     
         16 . The method of  claim 13 , wherein the interferon-alpha is selected from interferon alpha-2a, interferon alpha-2b, or a purified interferon alpha product and the amount of interferon-alpha administered is from 2 to 10 million IU per week on a weekly, TIW, QOD or daily basis.  
     
     
         17 . The method of  claim 16 , wherein the interferon-alpha administered is interferon-alpha-2b and the amount of interferon-alpha is administered 3 million IU TIW.  
     
     
         18 . The method of  claim 13 , wherein the interferon-alpha administered is consensus interferon and the amount of interferon-alpha administered is from 1 to 20 micrograms per week on a weekly, TIW, QOD or daily basis.  
     
     
         19 . The method of  claim 13 , wherein the interferon-alpha administered is a pegylated interferon alpha-2b and the amount of interferon-alpha administered is from 0.5 to 2.0 micrograms/kilogram per week on a weekly, TIW, QOD or daily basis.  
     
     
         20 . The method of  claim 13 , wherein the interferon-alpha administered is a pegylated interferon alpha-2a and the amount of interferon-alpha administered is from 20 to 250 micrograms/kilogram per week on a weekly, TIW, QOD or daily basis.  
     
     
         21 . A method of treating a patient having chronic hepatitis C infection to eradicate detectable HCV-RNA comprising administering a therapeutically effective amount of ribavirin and a therapeutically effective amount of interferon-alpha for a time period of 60 to 80 weeks, such that at least about 50% of the patients having no detectable HCV-RNA at the end of said 60 to 80 week period also have no detectable HCV-RNA for at least 24 weeks after the end of said administration.  
     
     
         22 . The method of  claim 21 , wherein at least about 60% of the patients having no detectable HCV-RNA at the end of said 60 to 80 week period also have no detectable HCV-RNA for at least 24 weeks after the end of said administration.  
     
     
         23 . The method of  claim 21 , wherein the amount of ribavirin administered is from 400 to 1200 mg per day.  
     
     
         24 . The method of  claim 21 , wherein the amount of ribavirin administered is from 800 to 1200 mg per day.  
     
     
         25 . The method of  claim 23 , wherein the interferon-alpha administered is selected from interferon alpha-2a, interferon alpha-2b, a consensus interferon, a purified interferon alpha product or a pegylated interferon-alpha.  
     
     
         26 . The method of  claim 23 , wherein the interferon-alpha is selected from interferon alpha-2a, interferon alpha-2b, or a purified interferon alpha product and the amount of interferon-alpha administered is from 2 to 10 million IU per week on a weekly, TIW, QOD or daily basis.  
     
     
         27 . The method of  claim 24 , wherein the interferon-alpha administered is interferon-alpha-2b and the amount of interferon-alpha is administered 3 million IU TIW.  
     
     
         28 . The method of  claim 23 , wherein the interferon-alpha administered is consensus interferon and the amount of interferon-alpha administered is from 1 to 20 micrograms per week on a weekly, TIW, QOD or daily basis.  
     
     
         29 . The method of  claim 23 , wherein the interferon-alpha administered is a pegylated interferon alpha-2b and the amount of interferon-alpha administered is from 0.5 to 2.0 micrograms/kilogram per week on a weekly, TIW, QOD or daily basis.  
     
     
         30 . The method of  claim 23 , wherein the interferon-alpha administered is a pegylated interferon alpha-2a and the amount of interferon-alpha administered is from 20 to 250 micrograms/kilogram per week on a weekly, TIW, QOD or daily basis.  
     
     
         31 . A method of treating a patient having chronic hepatitis C infection having HCV genotype other than type 1 and having a viral load of less than or equal to 2 million copies per ml of serum as measured by HCV-RNA quantitative PCR to eradicate detectable HCV-RNA comprising administering a therapeutically effective amount of ribavirin and a therapeutically effective amount of interferon-alpha for a time period of 20 to 30 weeks, such that at least about 70% of the patients having no detectable HCV-RNA at the end of said 20 to 30 week period also have no detectable HCV-RNA for at least 24 weeks after the end of said administration.  
     
     
         32 . The method of  claim 31 , wherein at least about 80% of the patients having no detectable HCV-RNA at the end of said 20 to 30 week period also have no detectable HCV-RNA for at least 24 weeks after the end of said administration.  
     
     
         33 . The method of  claim 31 , wherein the amount of ribavirin administered is from 400 to 1200 mg per day.  
     
     
         34 . The method of  claim 31 , wherein the amount of ribavirin administered is from 800 to 1200 mg per day.  
     
     
         35 . The method of  claim 33 , wherein the interferon-alpha administered is selected from interferon alpha-2a, interferon alpha-2b, a consensus interferon, a purified interferon alpha product or a pegylated interferon-alpha.  
     
     
         36 . The method of  claim 33 , wherein the interferon-alpha, is selected from interferon alpha-2a, interferon alpha-2b, or a purified interferon alpha product and the amount of interferon-alpha administered is from 2 to 10 million IU per week on a weekly, TIW, QOD or daily basis.  
     
     
         37 . The method of  claim 34 , wherein the interferon-alpha administered is interferon-alpha-2b and the amount of interferon-alpha is administered 3 million IU TIW.  
     
     
         38 . The method of  claim 33 , wherein the interferon-alpha administered is consensus interferon and the amount of interferon-alpha administered is from 1 to 20 micrograms per week on a weekly, TIW, QOD or daily basis.  
     
     
         39 . The method of  claim 33 , wherein the interferon-alpha administered is a pegylated interferon alpha-2b and the amount of interferon-alpha administered is from 0.5 to 2.0 micrograms/kilogram per week on a weekly, TIW, QOD or daily basis.  
     
     
         40 . The method of  claim 33 , wherein the interferon-alpha administered is a pegylated interferon alpha-2a and the amount of interferon-alpha administered is from 20 to 250 micrograms/kilogram per week on a weekly, TIW, QOD or daily basis.  
     
     
         41 . A method of treating a patient having chronic hepatitis C infection having HCV genotype other than type 1 and having a viral load of greater than 2 million copies as measured by HCV-RNA/qPCR to eradicate detectable HCV-RNA comprising administering a therapeutically effective amount of ribavirin and a therapeutically effective amount of interferon-alpha for a time period of 20 to 30 weeks, such that at least about 50% of the patients having no detectable HCV-RNA at the end of said 20 to 30 week period also have no detectable HCV-RNA for at least 24 weeks after the end of said administration.  
     
     
         42 . The method of  claim 41 , wherein at least about 60% of the patients having no detectable HCV-RNA at the end of said 20 to 30 week period also have no detectable HCV-RNA for at least 24 weeks after the end of said administration.  
     
     
         43 . The method of  claim 41 , wherein the amount of ribavirin administered is from 400 to 1200 mg per day.  
     
     
         44 . The method of  claim 41 , wherein the amount of ribavirin administered is from 800 to 1200 mg per day.  
     
     
         45 . The method of  claim 43 , wherein the interferon-alpha administered is selected from interferon alpha-2a, interferon alpha-2b, a consensus interferon, a purified interferon alpha product or a pegylated interferon-alpha.  
     
     
         46 . The method of  claim 43 , wherein the interferon-alpha is selected from interferon alpha-2a, interferon alpha-2b, or a purified interferon alpha product and the amount of interferon-alpha administered is from 2 to 10 million IU per week on a weekly, TIW, QOD or daily basis.  
     
     
         47 . The method of  claim 44 , wherein the interferon-alpha administered is interferon-alpha-2b and the amount of interferon-alpha is administered 3 million IU TIW.  
     
     
         48 . The method of  claim 43 , wherein the interferon-alpha administered is consensus interferon and the amount of interferon-alpha administered is from 1 to 20 micrograms per week on a weekly, TIW, QOD or daily basis.  
     
     
         49 . The method of  claim 43 , wherein the interferon-alpha administered is a pegylated interferon alpha-2b and the amount of interferon-alpha administered is from 0.5 to 2.0 micrograms/kilogram per week on a weekly, TIW, QOD or daily basis.  
     
     
         50 . The method of  claim 43 , wherein the interferon-alpha administered is a pegylated interferon alpha-2a and the amount of interferon-alpha administered is from 20 to 250 micrograms/kilogram per week on a weekly, TIW, QOD or daily basis.  
     
     
         51 . A method of treating a patient having chronic hepatitis C infection having HCV genotype type 1 and having a viral load of less than or equal to 2 million copies as measured by HCV-RNA/qPCR to eradicate detectable HCV-RNA comprising administering a therapeutically effective amount of ribavirin and a therapeutically effective amount of interferon-alpha for a time period of 20 to 30 weeks, such that at least about 30% of the patients having no detectable HCV-RNA at the end of said 20 to 30 week period also have no detectable HCV-RNA for at least 24 weeks after the end of said administration.  
     
     
         52 . The method of  claim 51 , wherein at least about 40% of the patients having no detectable HCV-RNA at the end of said 20 to 30 week period also have no detectable HCV-RNA for at least 24 weeks after the end of said administration.  
     
     
         53 . The method of  claim 51 , wherein the amount of ribavirin administered is from 400 to 1200 mg per day.  
     
     
         54 . The method of  claim 51 , wherein the amount of ribavirin administered is from 800 to 1200 mg per day.  
     
     
         55 . The method of  claim 53 , wherein the interferon-alpha administered is selected from interferon alpha-2a, interferon alpha-2b, a consensus interferon, a purified interferon alpha product or a pegylated interferon-alpha.  
     
     
         56 . The method of  claim 53 , wherein the interferon-alpha is selected from interferon alpha-2a, interferon alpha-2b, or a purified interferon alpha product and the amount of interferon-alpha administered is from 2 to 10 million IU per week on a weekly, TIW, QOD or daily basis.  
     
     
         57 . The method of  claim 54 , wherein the interferon-alpha administered is interferon-alpha-2b and the amount of interferon-alpha is administered 3 million IU TIW.  
     
     
         58 . The method of  claim 53 , wherein the interferon-alpha administered is consensus interferon and the amount of interferon-alpha administered is from 1 to 20 micrograms per week on a weekly, TIW, QOD or daily basis.  
     
     
         59 . The method of  claim 53 , wherein the interferon-alpha administered is a pegylated interferon alpha-2b and the amount of interferon-alpha administered is from 0.5 to 2.0 micrograms/kilogram per week on a weekly, TIW, QOD or daily basis.  
     
     
         60 . The method of  claim 53 , wherein the interferon-alpha administered is a pegylated interferon alpha-2a and the amount of interferon-alpha administered is from 20 to 250 micrograms/kilogram per week on a weekly, TIW, QOD or daily basis.  
     
     
         61 . A method of treating a patient having chronic hepatitis C infection having HCV genotype type 1 and having a viral load of greater than 2 million copies as measured by HCV-RNA/qPCR to eradicate detectable HCV-RNA comprising administering a therapeutically effective amount of ribavirin and a therapeutically effective amount of interferon-alpha for a time period of 20 to 30 weeks, such that at least about 15% of the patients having no detectable HCV-RNA at the end of said 20 to 30 week period also have no detectable HCV-RNA for at least 24 weeks after the end of said administration.  
     
     
         62 . The method of  claim 61 , wherein at least about 20% of the patients having no detectable HCV-RNA at the end of said 20 to 30 week period also have no detectable HCV-RNA for at least 24 weeks after the end of said administration.  
     
     
         63 . The method of  claim 61 , wherein the amount of ribavirin administered is from 400 to 1200 mg per day.  
     
     
         64 . The method of  claim 61 , wherein the amount of ribavirin administered is from 800 to 1200 mg per day.  
     
     
         65 . The method of  claim 63 , wherein the interferon-alpha administered is selected from interferon alpha-2a, interferon alpha-2b, a consensus interferon, a purified interferon alpha product or a pegylated interferon-alpha.  
     
     
         66 . The method of  claim 63 , wherein the interferon-alpha is selected from interferon alpha-2a, interferon alpha-2b, or a purified interferon alpha product and the amount of interferon-alpha administered is from 2 to 10 million IU per week on a weekly, TIW, QOD or daily basis.  
     
     
         67 . The method of  claim 64 , wherein the interferon-alpha administered is interferon-alpha-2b and the amount of interferon-alpha is administered 3 million IU TIW.  
     
     
         68 . The method of  claim 63 , wherein the interferon-alpha administered is consensus interferon and the amount of interferon-alpha administered is from 1 to 20 micrograms per week on a weekly, TIW, QOD or daily basis.  
     
     
         69 . The method of  claim 63 , wherein the interferon-alpha administered is a pegylated interferon alpha-2b and the amount of interferon-alpha administered is from 0.5 to 2.0 micrograms/kilogram per week on a weekly, TIW, QOD or daily basis.  
     
     
         70 . The method of  claim 63 , wherein the interferon-alpha administered is a pegylated interferon alpha-2a and the amount of interferon-alpha administered is from 20 to 250 micrograms/kilogram per week on a weekly, TIW, QOD or daily basis.