Combination Therapy for Chronic Hepatitis C Infection

Summary

Background: \- GS-7977, GS-5885, GS-9669, and GS-9451 are new drugs for treating hepatitis C virus (HCV) infection. GS-7977 may help treat the infection when used with other treatments like interferon therapy. GS-5885, and GS-9669, and GS-9451 also lower the amount of HCV in the body. Researchers want to see whether GS-7977 can be combined with any of the other three drugs to treat HCV infection. Some participants will take GS-7977 and GS-5885. Others will take GS-7977, GS-5885 and GS-9669 or GS-7977, GS-5885 and GS-9451. Objectives: \- To see whether GS-7977 with GS-5885 alone or in combination with either GS-9669 or 9451 can be used to treat HCV infection. Eligibility: Individuals at least 18 years of age who have chronic HCV infection and have never been treated for it. Individuals at least 18 years of age who have chronic HCV infection and have not responded to interferon therapy. Individuals at least 18 years of age who have chronic HCV infection with advanced liver disease and have never been treated for HCV Design: Participants will be screened with a physical exam and medical history. Blood samples will be collected. A liver biopsy may also be performed. Some participants will take the two study drugs and some will take three study drugs. Those who take GS-7977 and GS-5885 will have one daily tablet named fixed dose combination or FDC. Those who take GS-7977 and CS-9669 will have three daily tablets taken once daily. Those who take GS-7977 and GS-5885 and GS-9451 will take 2 pills once a day. GS-7977 and GS-5885 will be combined in one pill and GS-9451 will be in another pill. Treatment will be monitored with frequent blood tests. These tests will check liver function and the level of HCV infection. Participants may have other blood tests as needed for treatment. Participants will have 4, 6 or 12 weeks of treatment depending on which study drugs are scheduled to take. After they complete their schedule, they will stop treatment with the study drugs. They may also have another liver biopsy. Participants will have regular follow-up visits over the next 48 weeks. They will have physical exams and provide blood samples....

Timeline

Start

2013-01

Primary completion

2015-08

Completion

2015-08

Publications

• Background Armstrong GL, Wasley A, Simard EP, McQuillan GM, Kuhnert WL, Alter MJ. The prevalence of hepatitis C virus infection in the United States, 1999 through 2002. Ann Intern Med. 2006 May 16;144(10):705-14. doi: 10.7326/0003-4819-144-10-200605160-00004.
• Background Serfaty L, Aumaitre H, Chazouilleres O, Bonnand AM, Rosmorduc O, Poupon RE, Poupon R. Determinants of outcome of compensated hepatitis C virus-related cirrhosis. Hepatology. 1998 May;27(5):1435-40. doi: 10.1002/hep.510270535.
• Background Davis GL, Albright JE, Cook SF, Rosenberg DM. Projecting future complications of chronic hepatitis C in the United States. Liver Transpl. 2003 Apr;9(4):331-8. doi: 10.1053/jlts.2003.50073.
• Townsend K, Petersen T, Gordon LA, Kohli A, Nelson A, Seamon C, Gross C, Tang L, Osinusi A, Polis MA, Masur H, Kottilil S. Effect of HIV co-infection on adherence to a 12-week regimen of hepatitis C virus therapy with ledipasvir and sofosbuvir. AIDS. 2016 Jan;30(2):261-6. doi: 10.1097/QAD.0000000000000903.
• Petersen T, Townsend K, Gordon LA, Sidharthan S, Silk R, Nelson A, Gross C, Calderon M, Proschan M, Osinusi A, Polis MA, Masur H, Kottilil S, Kohli A. High adherence to all-oral directly acting antiviral HCV therapy among an inner-city patient population in a phase 2a study. Hepatol Int. 2016 Mar;10(2):310-9. doi: 10.1007/s12072-015-9680-7. Epub 2015 Nov 26.
• Kohli A, Kattakuzhy S, Sidharthan S, Nelson A, McLaughlin M, Seamon C, Wilson E, Meissner EG, Sims Z, Silk R, Gross C, Akoth E, Tang L, Price A, Jolley TA, Emmanuel B, Proschan M, Teferi G, Chavez J, Abbott S, Osinusi A, Mo H, Polis MA, Masur H, Kottilil S. Four-Week Direct-Acting Antiviral Regimens in Noncirrhotic Patients With Hepatitis C Virus Genotype 1 Infection: An Open-Label, Nonrandomized Trial. Ann Intern Med. 2015 Dec 15;163(12):899-907. doi: 10.7326/M15-0642. Epub 2015 Nov 24.
• Wilson EM, Kattakuzhy S, Sidharthan S, Sims Z, Tang L, McLaughlin M, Price A, Nelson A, Silk R, Gross C, Akoth E, Mo H, Subramanian GM, Pang PS, McHutchison JG, Osinusi A, Masur H, Kohli A, Kottilil S. Successful Retreatment of Chronic HCV Genotype-1 Infection With Ledipasvir and Sofosbuvir After Initial Short Course Therapy With Direct-Acting Antiviral Regimens. Clin Infect Dis. 2016 Feb 1;62(3):280-288. doi: 10.1093/cid/civ874. Epub 2015 Oct 31.
• Kohli A, Kapoor R, Sims Z, Nelson A, Sidharthan S, Lam B, Silk R, Kotb C, Gross C, Teferi G, Sugarman K, Pang PS, Osinusi A, Polis MA, Rustgi V, Masur H, Kottilil S. Ledipasvir and sofosbuvir for hepatitis C genotype 4: a proof-of-concept, single-centre, open-label phase 2a cohort study. Lancet Infect Dis. 2015 Sep;15(9):1049-1054. doi: 10.1016/S1473-3099(15)00157-7. Epub 2015 Jul 14.
• Kohli A, Osinusi A, Sims Z, Nelson A, Meissner EG, Barrett LL, Bon D, Marti MM, Silk R, Kotb C, Gross C, Jolley TA, Sidharthan S, Petersen T, Townsend K, Egerson D, Kapoor R, Spurlin E, Sneller M, Proschan M, Herrmann E, Kwan R, Teferi G, Talwani R, Diaz G, Kleiner DE, Wood BJ, Chavez J, Abbott S, Symonds WT, Subramanian GM, Pang PS, McHutchison J, Polis MA, Fauci AS, Masur H, Kottilil S. Virological response after 6 week triple-drug regimens for hepatitis C: a proof-of-concept phase 2A cohort study. Lancet. 2015 Mar 21;385(9973):1107-13. doi: 10.1016/S0140-6736(14)61228-9. Epub 2015 Jan 13.
• Osinusi A, Kohli A, Marti MM, Nelson A, Zhang X, Meissner EG, Silk R, Townsend K, Pang PS, Subramanian GM, McHutchison JG, Fauci AS, Masur H, Kottilil S. Re-treatment of chronic hepatitis C virus genotype 1 infection after relapse: an open-label pilot study. Ann Intern Med. 2014 Nov 4;161(9):634-8. doi: 10.7326/M14-1211.

Drugs

Indications