GS-7977 With Ribavirin for Hepatitis C (SPARE)

Summary

Background: \- GS-7977 is a new drug that is being developed to treat hepatitis C infection. It works by blocking the hepatitis C virus from dividing in the body. This medication has been used along with other medications commonly used to treat hepatitis C, such as interferon and ribavirin. When used with interferon and ribavirin, GS-7977 seems to be very effective in eliminating the hepatitis C virus from the body. However, interferon can have serious side effects, so researchers want to see if GS-7977 can work by itself or with only ribavirin. Objectives: \- To test the safety and effectiveness of GS-7977 alone or given with ribavirin for hepatitis C infection. Eligibility: \- Individuals at least 18 years of age who have hepatitis C with liver disease, and have never received drugs for it. Design: * This study will require multiple clinic visits over 18 months. A liver biopsy will be required before the start of the study if participants have not had one within the past 3 years. * Participants will be screened with a medical history and physical exam. * Participants will have either GS-7977 alone or GS-7977 with ribavirin. GS-7977 is taken by mouth once a day. Ribavirin is taken by mouth in the morning and evening. * Participants will have study visits on Days 1, 3, 5, 7, 10, and 14. These visits will involve regular blood tests and symptom monitoring. * After the second week, participants will have study visits during Weeks 3, 4, 6, 8, 12, 16, and 20. Blood and urine tests will be given to study virus levels in the body, and symptoms will be discussed. * Participants will stop receiving the study drugs at Week 24. * Followup clinic visits with blood tests will take place in Weeks 28, 36, 48, 52, 60, and 72. Another liver biopsy will be performed at 48 weeks. * Some participants may also be part of a smaller study. This study involves frequent blood draws to study drug and virus levels in the blood. The study will require a 36-hour hospital inpatient visit.

Timeline

Start

2011-09

Primary completion

2013-03

Completion

2014-07

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 Kim WR. The burden of hepatitis C in the United States. Hepatology. 2002 Nov;36(5 Suppl 1):S30-4. doi: 10.1053/jhep.2002.36791.
• Background Kim WR, Brown RS Jr, Terrault NA, El-Serag H. Burden of liver disease in the United States: summary of a workshop. Hepatology. 2002 Jul;36(1):227-42. doi: 10.1053/jhep.2002.34734. No abstract available.
• Sidharthan S, Kohli A, Sims Z, Nelson A, Osinusi A, Masur H, Kottilil S. Utility of hepatitis C viral load monitoring on direct-acting antiviral therapy. Clin Infect Dis. 2015 Jun 15;60(12):1743-51. doi: 10.1093/cid/civ170. Epub 2015 Mar 2.
• Meissner EG, Wu D, Osinusi A, Bon D, Virtaneva K, Sturdevant D, Porcella S, Wang H, Herrmann E, McHutchison J, Suffredini AF, Polis M, Hewitt S, Prokunina-Olsson L, Masur H, Fauci AS, Kottilil S. Endogenous intrahepatic IFNs and association with IFN-free HCV treatment outcome. J Clin Invest. 2014 Aug;124(8):3352-63. doi: 10.1172/JCI75938. Epub 2014 Jul 1.
• Osinusi A, Meissner EG, Lee YJ, Bon D, Heytens L, Nelson A, Sneller M, Kohli A, Barrett L, Proschan M, Herrmann E, Shivakumar B, Gu W, Kwan R, Teferi G, Talwani R, Silk R, Kotb C, Wroblewski S, Fishbein D, Dewar R, Highbarger H, Zhang X, Kleiner D, Wood BJ, Chavez J, Symonds WT, Subramanian M, McHutchison J, Polis MA, Fauci AS, Masur H, Kottilil S. Sofosbuvir and ribavirin for hepatitis C genotype 1 in patients with unfavorable treatment characteristics: a randomized clinical trial. JAMA. 2013 Aug 28;310(8):804-11. doi: 10.1001/jama.2013.109309.

Drugs

Indications