Reversal of Hepatic Impairment in Patients With Hepatitis C Virus (HCV) and Early Decompensation of Cirrhosis

• Status: Terminated
• Trial end date: 2016-07-18
• Target enrollment: 0
• Participant gender: All

Summary

1. Achieve sustained virologic response (SVR) in patients infected with HCV genotype 1, cirrhosis, and early clinical decompensation using 12 weeks of Olysio/Sovaldi/Ribavirin (or known as: Simeprevir(SMV)/Sofosbuvir(SOF)/Ribavirin (RBV).

2. Hepatic improvement during and after Simeprevir(SMV)/Sofosbuvir(SOF)/Ribavirin(RBV) treatment using a new test of liver function, HepQuant-SHUNT.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Colorado, Denver
• Collaborator: Janssen Scientific Affairs, LLC
• Treatments: Ribavirin; Sofosbuvir

Criteria

Inclusion Criteria:

1. HCV genotype 1 infection (all subtypes and Q80K a type of mutation are allowed), and have been approved by a third party payer for the FDA-approved combination of sofosbuvir (SOF) plus ribavirin. The study drug, simeprevir (SMV)

2. Biopsy proven cirrhosis, or clinical cirrhosis with APRI (AST to Platelet Ratio Index to determine clinical cirrhosis)> 2, Fibrotest > 0.75, or Fibroscan > 12.5 Results Stiffness (kPa).

3. MELD 10 or less

4. Expected survival without liver transplantation of >1 year

5. Patients with Hepatocellular carcinoma (HCC) are included as long as disease MELD is 10 or less, and anticipated time to transplant is >1 year. An example, might be a patient with a subcentimeter HCC who is undergoing serial imaging to document tumor growth to tumor diameter >2 cm prior to listing for transplantation (in order to secure MELD exception). In this case, there could be a time lapse of 3 months or more while monitoring tumor growth, and a further time lapse of 9 months or more until the time of transplantation.

6. Patients with TIPS or Portal Vein Thrombosis may be included. -

Exclusion Criteria:

1. Inability to provide informed consent

2. Known hypersensitivity or serious adverse reaction to any of the study drugs

3. Age <18 or >80 years

4. Pregnancy as determined by subject reporting and urine dipstick testing at screening.

5. Other underlying chronic liver disease - examples that would exclude a patient from participating include but are not limited to nonalcoholic liver disease, alcoholic liver disease, hepatitis B, hemochromatosis, and autoimmune liver disease.

6. Serious other underlying medical condition - examples include but are not limited to unstable cardiovascular, coronary, or pulmonary disease including right and left sided heart failure, active malignancy other than HCC, or serious infection.

7. Estimated creatinine clearance < 30 mL min-1 1.73 m2 surface area (BSA)

8. Hemoglobin <10 g/dL

9. Neutrophils <500 /μL

10. Platelets <50,000 /μL

11. Bilirubin >4 mg/dL

12. Albumin < 2.8 g/dL

13. Blood Clotting: International Normalised Ratio (INR) > 2

14. MELD >10

15. Child-Turcotte-Pugh class B or C; or, CTP score >7

16. Conditions that would affect the absorption of orally administered cholate used in the HepQuant® test - such as, extensive intestinal resection, diabetic gastroparesis, and ileal disease or resection.

17. Concomitant use of both beta-blocker and ACE inhibitor

18. Subjects taking any other medications with significant drug drug interactions related to the study medications (sofosbuvir, simeprevir, or ribavirin) who cannot discontinue or substitute that medication, will be excluded.