Safety, Tolerability, and Efficacy of 24 Weeks Simeprevir+Sofosbuvir for Chronic Hepatitis C Genotype 1

PT-NANBH Clinical Trial

Official title:

Safety, Tolerability, and Efficacy of Simeprevir 150 mg Daily Plus Sofosbuvir 400 mg Daily for 24 Weeks in Patients With Chronic Hepatitis C Genotype 1 With CPT Score of 6 or Lower Who Are IFN-Intolerant or Unwilling to be Treated With IFN

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02485080
• Other study ID #: 33431
• Status: Withdrawn
• Phase: Phase 4
• First received: June 23, 2015
• Last updated: October 12, 2016
• Start date: September 2015
• Est. completion date: January 2016

Study information

• Verified date: October 2016
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Data and Safety Monitoring BoardUnited States: Federal GovernmentUnited States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The goal of this pilot study is to examine both efficacy and tolerability in patients with HCV genotype 1 and mild decompensation with Child-Pugh-Turcott score of 6 or lower. The CPT score is used to assess the prognosis of chronic liver diseases, as well as the required strength and treatment and necessity of liver transplantation. A higher CPT score denotes higher necessity of liver transplantation.

Description:

Key objectives of this study include:

1. To describe efficacy (SVR) in a special population of patients with chronic hepatitis C who are not willing or not candidates for IFN-based therapy.

2. To describe safety, tolerability, and treatment persistency in this patient population with advanced liver disease.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: January 2016
• Est. primary completion date: January 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 72 Years

Eligibility

Inclusion criteria:

1. Adult 18-72 years

2. Cirrhosis: defined by stage 4 on biopsy or noninvasive tests or presence of splenomegaly and platelet of 130K or lower, or presence of shrunken nodular liver on CT or MRI, or presence of varices or encephalopathy or ascites.

3. HCV genotype 1 or indeterminate and later assessed at Screening and confirmed as genotype 1

Exclusion criteria:

1. Uncontrolled ascites, uncontrolled hepatic encephalopathy, or uncontrolled esophageal/gastric varices

2. Co-infection with HIV or hepatitis B (HBV)

3. CPT 7 or above, or MELD >10

4. Total bilirubin 4.0 mg/dL or above

5. CrCl (creatinine clearance) < 30 mL/min

6. Any unstable active medical illnesses.

7. Active use of illicit substances, alcohol, or smoking.

8. Any malignancy within last 5 years except for basal cell skin cancer that has been adequately treated or HCC within Milan or UCSF criteria, which will be acceptable

9. Any prior treatment with direct acting antivirals (approved or investigational), including HCV protease inhibitors, such as SMV. Patients who received prior treatment with SOF, and/or NS5A inhibitors (e.g. ledipasvir or Daclatasvir) can be included in this study

10. Platelet < 30 K/uL

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis C
• Hepatitis C, Chronic
• Hepatitis, Chronic
• PT-NANBH

Intervention

Drug:
• Simeprevir

• Sofosbuvir

Locations

Country	Name	City	State
United States	Yale University Medical Center	New Haven	Connecticut
United States	Stanford University Medical Center	Palo Alto	California

Sponsors (3)

Lead Sponsor	Collaborator
Stanford University	Janssen Scientific Affairs, LLC, Yale University

Country where clinical trial is conducted

United States, 

References & Publications (3)

Carrión JA, Martínez-Bauer E, Crespo G, Ramírez S, Pérez-del-Pulgar S, García-Valdecasas JC, Navasa M, Forns X. Antiviral therapy increases the risk of bacterial infections in HCV-infected cirrhotic patients awaiting liver transplantation: A retrospective study. J Hepatol. 2009 Apr;50(4):719-28. doi: 10.1016/j.jhep.2008.11.015. Epub 2008 Dec 29. — View Citation

Iacobellis A, Siciliano M, Perri F, Annicchiarico BE, Leandro G, Caruso N, Accadia L, Bombardieri G, Andriulli A. Peginterferon alfa-2b and ribavirin in patients with hepatitis C virus and decompensated cirrhosis: a controlled study. J Hepatol. 2007 Feb;46(2):206-12. Epub 2006 Oct 20. — View Citation

Roche B, Samuel D. Hepatitis C virus treatment pre- and post-liver transplantation. Liver Int. 2012 Feb;32 Suppl 1:120-8. doi: 10.1111/j.1478-3231.2011.02714.x. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sustained virologic response (SVR) HCV RNA PCR <25 IU/mL 12 weeks post-treatment		12 weeks after end of treatment or virologic response after liver transplantation, whichever comes first, assessed up to 12 weeks after end of treatment	No
Secondary	Serious adverse events, adverse events grade 3 and above		24 weeks while on treatment and 24 weeks after end of treatment	Yes

External Links

•   OLYSIO (Simeprevir) package insert
•   Recommendations for Testing, Managing, and Treating Hepatitis C by the American Association for the Study of Liver Diseases and Infectious Disease Society of America
•   SOLVALDI (Sofosbuvir) package insert