Clinical trial NCT02485080: Safety, Tolerability, and Efficacy of 24 Weeks Simeprevir+Sofosbuvir for Chronic Hepatitis C Genotype 1
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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE4
Conditions: PT-NANBH
Keywords: hepatitis C
liver transplantation
genotype 1
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: Janssen Scientific Affairs, LLC
name: Yale University
First posted: 2015-06-30
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 72
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Sustained virologic response (SVR) HCV RNA PCR <25 IU/mL 12 weeks post-treatment
timeFrame: 12 weeks after end of treatment or virologic response after liver transplantation, whichever comes first, assessed up to 12 weeks after end of treatment
Secondary outcomes:
measure: Serious adverse events, adverse events grade 3 and above
timeFrame: 24 weeks while on treatment and 24 weeks after end of treatment
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford University Medical Center
state: California
city: New Haven
country: United States
facility: Yale University Medical Center
state: Connecticut
Study officials:
affiliation: Stanford University
name: Mindie H Nguyen, MD, MAS
role: PRINCIPAL_INVESTIGATOR
References:
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.
citation: Carrion JA, Martinez-Bauer E, Crespo G, Ramirez S, Perez-del-Pulgar S, Garcia-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.
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. doi: 10.1016/j.jhep.2006.08.020. Epub 2006 Oct 20.